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Intra‐articular corticosteroid for knee osteoarthritis

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Referencias

References to studies included in this review

Beyaz 2012 {published data only}

Beyaz S G. Comparison of efficacy of intra‐articular morphine and steroid in patients with knee osteoarthritis. Journal of Anaesthesiology Clinical Pharmacology 2012;28(4):496‐500.

Campos 2013 {published data only}

Campos G C. Evaluation of the effect of adding corticosteroid to viscosupplementation: A prospective and randomized study. Osteoarthritis and Cartilage 2011;19:S236.
Campos G C, Rezende M U, Fruchi R, Pasqualin T, Hissadomi M I. Adding triamcinolone to viscosupplementation: One year outcome of randomized trial. Osteoarthritis and Cartilage 2014;22:S198.
Campos G C, Rezende M U, Pailo A F, Frucchi R, Camargo O P. Adding triamcinolone improves viscosupplementation: A randomized clinical trial. Clinical Orthopaedics and Related Research 2013;471(2):613‐20.
Campos G C, Rezende M U, Pailo A F, Frucchi R, Pasqualin T. Evaluation of the effect of adding corticosteroid to viscosupplementation: A prospective and randomized study. Osteoarthritis and Cartilage 2012;20:S169‐70.

Castro 2007 {published data only}

Castro M, Font P, Escudero A, Frias G, Muñoz E, Collantes E. Evaluation of effectiveness of five modalities of intraarticular treatment in patients with osteoarthritis of the knee. Annals of the Rheumatic Diseases 2007;66(Suppl II):515.

Cederlof 1966 {published data only}

Cederlof S, Jonson G. Intraarticular prednisolone injection for osteoarthritis of the knee. A double blind test with placebo. Acta Chirurgica Scandinavica 1966;132(5):532‐7.

Chao 2010 {published data only}

Chao J, Wu C, Sun B, Hose M K, Quan A, Hughes T H, et al. Inflammatory characteristics on ultrasound predict poorer long‐term response to intraarticular corticosteroid injections in knee osteoarthritis. Journal of Rheumatology 2010;37(3):650‐5.
Chao J, Wu C, Sun B, Hose M, Quan A, May S, et al. Inflammatory characteristics on ultrasound predict poorer long‐term response to intraarticular corticosteroid injections in knee osteoarthritis. Osteoarthritis and Cartilage 2009;17:S153.

Dieppe 1980 {published data only}

Dieppe P A, Sathapatayavongs B, Jones H E. Intra‐articular steroids in osteoarthritis. Rheumatology and Rehabilitation 1980;19(4):212‐7.

Di Sante 2012 {published data only}

Di Sante L, Paoloni M, Dimaggio M, Colella L, Cerino A, Bernetti A, et al. Ultrasound‐guided aspiration and corticosteroid injection compared to horizontal therapy for treatment of knee osteoarthritis complicated with Baker's cyst: a randomized controlled trial. European Journal of Physical & Rehabilitation Medicine 2012;48(4):561‐7.

Frías 2004 {published data only}

Frías G, Caracuel M A, Escudero A, Rumbao J, Pérez‐Gujo V, Carmen Castro M, et al. Assessment of the efficacy of joint lavage versus joint lavage plus corticoids in patients with osteoarthritis of the knee. Current Medical Research and Opinion 2004;20(6):861‐7.

Friedman 1980 {published data only}

Friedman D M, Moore M E. The efficacy of intraarticular steroids in osteoarthritis: A double‐blind study. Journal of Rheumatology 1980;7(6):850‐6.

Gaffney 1995 {published data only}

Gaffney K, Ledingham J, Perry J D. Intra‐articular triamcinolone hexacetonide in knee osteoarthritis: Factors influencing the clinical response. Annals of the Rheumatic Diseases 1995;54(5):379‐81.

Grecomoro 1992 {published data only}

Grecomoro G, Piccione F, Letizia G. Therapeutic synergism between hyaluronic acid and dexamethasone in the intra‐articular treatment of osteoarthritis of the knee: a preliminary open study. Current Medical Research and Opinion 1992;13(1):49‐55.

Henriksen 2015 {published data only}

Henriksen M, Christensen R, Klokker L, Bartholdy C, Bandak E, Ellegaard K, et al. Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee. A randomized clinical trial. JAMA Internal Medicine 2015;175(6):923‐30. [DOI: 10.1001/jamainternmed.2015.0461]

Jones 1996 {published data only}

Jones A, Doherty M. Intra‐articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response. Annals of the Rheumatic Diseases 1996;55(11):829‐32.

Lyons 2005 {published data only}

Lyons C, Majeed A, Banarsee R. Effectiveness of high volume intra‐articular injection of cortisone and lignocaine in osteoarthritis of the knee. Pilot study. North & West London journal of general practice: NWLJGP 2005;11(1):23‐8.

Miller 1958 {published data only}

Miller J H, White J, Norton T H. The value of intra‐articular injections in osteoarthritis of the knee. Journal of Bone & Joint Surgery ‐ British Volume 1958;40‐B(4):636‐43.

NCT00414427 {published data only}

NCT00414427. Using ultrasound to predict response to intraarticular corticosteroids in knee osteoarthritis. ClinicalTrials.gov (acessed 19 October 2015).

Ozturk 2006 {published data only}

Ozturk C, Atamaz F, Hepguler S, Argin M, Arkun R. The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1‐year, single‐blind, randomized study. Rheumatology International 2006;26(4):314‐9.

Petrella 2015 {published data only}

Petrella R J, Eamans P, Alleyne J, Maroney M. A prospective, multi‐center, randomized, double‐blind feasibility study to evaluate the safety and performance of hydros joint therapy and hydros‐ta joint therapy for management of pain associated with osteoarthritis in the knee. Osteoarthritis and Cartilage 2012;20:S172‐3.
Petrella R J, Emans P J, Alleyne J, Dellaert F, Gill D P, Maroney M. Safety and performance of Hydros and Hydros‐TA for knee osteoarthritis. A prospective, multicenter, randomized, double‐blind feasibility trial. BMC Musculoskeletal Disorders 2015;16:57:1‐9.

Popov 1989 {published data only}

Popov V V, Bunchuk N V, Apenysheva N P. Treatment of patients with gonarthrosis by intra‐articular administration of drugs. Klinicheskaia Meditsina (Moskva) 1989;67(4):104‐8.

Ravaud 1999 {published data only}

Ravaud P, Moulinier L, Giraudeau B, Ayral X, Guerin C, Noel E, et al. Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial. Arthritis & Rheumatology 1999;42(3):475‐82.

Raynauld 2003 {published data only}

Raynauld J P, Buckland‐Wright C, Ward R, Choquette D, Haraoui B, Martel‐Pelletier J, et al. Safety and efficacy of long‐term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double‐blind, placebo‐controlled trial. [Erratum appears in Arthritis & Rheumatology 2003 Nov;48(11):3300]. Arthritis & Rheumatology 2003;48(2):370‐7.

Schue 2011 {published data only}

Schue J R. Treatment of knee osteoarthritis with intraarticular infliximab may improve knee function and reduce synovial infiltration by macrophages: Proceedings of the ACR 2011 Conference. American College of Theumatology. 2011.

Smith 2003 {published data only}

Smith M D, Wetherall M, Darby T, Esterman A, Slavotinek J, Roberts‐Thomson P, et al. A randomized placebo‐controlled trial of artroscopic lavage versus lavage plus intra‐articular corticosteroids in the management of symptomatic osteoarthritis of the knee. Rheumatology 2003;42(12):1477‐85.
Smith M, Wetherall M, Roberts‐Thomson P, Ahem M. Is intra‐articular depot corticosteroid treatment effective in symptomatic osteoarthritis of the knee joint? [abstract]. Australian and New Zealand Journal of Medicine 2000;30(4):527.

Wright 1960 {published data only}

Wright V, Chandler G N, Morison R A, Hartfall S J. Intra‐articular therapy in osteo‐arthritis; comparison of hydrocortisone acetate and hydrocortisone tertiary‐butylacetate. Annals of the Rheumatic Diseases 1960;19:257‐61.

Yavuz 2012 {published data only}

Yavuz U, Sokucu S, Albayrak A, Ozturk K. Efficacy comparisons of the intraarticular steroidal agents in the patients with knee osteoarthritis. Rheumatology International 2012;32(11):3391‐6.

Young 2001 {published data only}

Young L, Katrib A, Cuello C, Vollmer‐Conna U, Bertouch J V, Roberts‐Thomson P J, et al. Effects of intraarticular glucocorticoids on macrophage infiltration and mediators of joint damage in osteoarthritis synovial membranes: findings in a double‐blind, placebo‐controlled study. Arthritis & Rheumatism 2001;44(2):343‐50.

Zhilyayev 2012 {published data only}

Zhilyayev E, Zagrebneva A, Glazunov A, Glazunov P, Alkhimenko T. Efficacy of intraarticular and periarticular glucocorticoid injections in patients with knee osteoarthritis: A randomized double‐blind study. International Journal of Rheumatic Diseases 2012;15:95.

References to studies excluded from this review

Abdulla 2013 {published data only}

Abdulla A, Adams N, Bone M, Elliott A M, Gaffin J, Jones D, et al. Guidance on the management of pain in older people. Age and Ageing 2013;42 Suppl 1:i1‐57.

Anonymous 1978 {published data only}

Anonymous. Intra‐articular steroids. British Medical Journal 1978;1:600‐1.

Anonymous 2011 {published data only}

Anonymous. Knee osteoarthritis. [Original report in American Family Physician. 2011 Jun 1;83(11):1287‐92; PMID: 21661710]. American Family Physician 2011;83:1294.

Arroll 2004 {published data only}

Arroll B, Goodyear‐Smith F. Corticosteroid injections for osteoarthritis of the knee: meta‐analysis. BMJ 2004;328:869.

Arroll 2005 {published data only}

Arroll B, Goodyear‐Smith F, Shoor S. Review: Intra‐articular corticosteroid injections are better than placebo for improving symptoms of knee osteoarthritis. Evidence‐Based Medicine 2005;10:23.

Avouac 2010 {published data only}

Avouac J, Vicaut E, Bardin T, Richette P. Efficacy of joint lavage in knee osteoarthritis: Meta‐analysis of randomized controlled studies. Rheumatology 2010;49:334‐40.

Baker 1969 {published data only}

Baker D M, Burland W L. Intra‐articular injection of corticosteroid for degenerative arthritis. Practitioner 1969;202:431‐2.

Bannuru 2013 {published data only}

Bannuru R R, McAlindon T E, Wong J B, Kent D, Schmid C. Comparative effectiveness of pharmacological interventions for knee osteoarthritis: A network meta‐analysis. Arthritis and Rheumatism 2013;65:S915‐6.

Bannuru 2014 {published data only}

Bannuru R R, Schmid C H, Sullivan M C, Kent D M, Wong J B, McAlindon T E. Differential response of placebo treatments in osteoarthritis trials: A systematic review and network meta‐analysis. Osteoarthritis and Cartilage 2014;22:S24‐5.

Bannuru 2015 {published data only}

Bannuru R R, Schmid C H, Kent D M, Vaysbrot E E, Wong J B, McAlindon T E. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: A systematic review and network meta‐analysis. Annals of Internal Medicine 2015;162:46‐54.

Baratham 2010 {published data only}

Baratham A, Lukert B P, Lindsley H B. Effects of intraarticular (IA) corticosteroid injections on bone markers and endogenous cortisol in patients with knee osteoarthritis (OA), a pilot study. Arthritis and Rheumatism 2010;62:943.

Bellamy 2005 {published data only}

Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD005328.pub2]

Bellamy 2006 {published data only}

Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD005328.pub2]

Bennell 2012 {published data only}

Bennell K L, Hunter D J, Hinman R S. Management of osteoarthritis of the knee. BMJ (Online) 2012;345:1‐8.

Bjordal 2007 {published data only}

Bjordal J M, Klovning A, Ljunggren A E, Slordal L. Short‐term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta‐analysis of randomised placebo‐controlled trials. European Journal of Pain 2007;11:125‐38.

Blanke 2008 {published data only}

Blanke M, Gusinde J, Dobre A, Brem M H. Treatment of knee osteoarthritis. MMW Fortschritte der Medizin 2008;150:26‐9; quiz 30.

Bourne 1985 {published data only}

Bourne I H. Injecting painful knees with triamcinolone. Practitioner 1985;229:33‐4.

Brys 2004 {published data only}

Brys D A. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. Journal of Bone & Joint Surgery ‐ American Volume 2004;86‐A:874; author reply 874‐5.

Canillas 2011 {published data only}

Canillas M, Kandavanam R, Reilly K. Do intra‐articular (IA) steroid injections relieve pain and improve outcomes beyond two weeks for patients with osteoarthritis (OA) of the knee. Journal ‐ Oklahoma State Medical Association 2011;104:262‐3.

Cats 1979b {published data only}

Cats A, JA I J, Davinova Y, Werthauer‐Rodrigues Pereira M, Blakemore C B, Steiner F J. The efficacy of intra‐articularly administered MYC 2095, triamcinolone hexacetonide and placebo in gonarthritis. A combined double‐blind clinical trial. Scandinavian Journal of Rheumatology 1979;8:199‐203.

Charalambous 2004 {published data only}

Charalambous C P. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. Journal of Bone & Joint Surgery ‐ American Volume 2004;86‐A:874; author reply 874.

Cheng 2012 {published data only}

Cheng O T, Souzdalnitski D, Vrooman B, Cheng J. Evidence‐based knee injections for the management of arthritis. Pain Medicine (United States) 2012;13:740‐53.

Courtney 2009 {published data only}

Courtney P, Doherty M. Editorial: Intra‐articular corticosteroid injection for osteoarthritis. International Journal of Clinical Rheumatology 2009;4:621‐5.

Douglas 2012 {published data only}

Douglas R J. Corticosteroid injection into the osteoarthritic knee: drug selection, dose, and injection frequency. International Journal of Clinical Practice 2012;66:699‐704.

Gait 2014 {published data only}

Gait A D, Hodgson R, Cootes T F, Marjanovic E J, Parkes M, O'Neill T W, et al. Late synovial enhancement detects effects of intraarticular steroids on synovitis better than synovial volume. Osteoarthritis and Cartilage 2014;22:S240‐1.

Garg 2013 {published data only}

Garg N, Deodhar A. A systematic review of comparative efficacy of various corticosteroid preparations for intra‐articular and soft tissue injections. Annals of the Rheumatic Diseases 2013;72:A720.

Garg 2014 {published data only}

Garg N, Perry L, Deodhar A. Intra‐articular and soft tissue injections, a systematic review of relative efficacy of various corticosteroids.. Clinical Rheumatology 2014;33:1695‐706.

Gerlag 2008a {published data only}

Gerlag D M, Tak P P. Prolonged effect of intra‐articularly administered corticosteroids in combination with arthroscopic lavage in patients with an inflammatory arthritis of the knee [Verlenging van het effect van intra‐articulair toegediende corticosteroiden door combinatie hiervan met artroscopische lavage bij patienten met een inflammatoire artritis van de knie]. Nederlands Tijdschrift Voor Geneeskunde 2008;152:1953‐5.

Godwin 2004 {published data only}

Godwin M, Dawes M. Intra‐articular steroid injections for painful knees. Systematic review with meta‐analysis. Canadian Family Physician 2004;50:241‐8.

Habib 2009 {published data only}

Habib G S. Systemic effects of intra‐articular corticosteroids. Clinical Rheumatology 2009;28:749‐56.

Habib 2010 {published data only}

Habib G S, Saliba W, Nashashibi M. Local effects of intra‐articular corticosteroids. Clinical Rheumatology 2010;29:347‐56.

Hepper 2009 {published data only}

Hepper C T, Halvorson J J, Duncan S T, Gregory A J M, Dunn W R, Spindler K P. The efficacy and duration of intra‐articular corticosteroid injection for knee osteoarthritis: A systematic review of level I studies. Journal of the American Academy of Orthopaedic Surgeons 2009;17:638‐46.

Hirsch 2013 {published data only}

Hirsch G, Kitas G, Klocke R. Intra‐articular corticosteroid injection in osteoarthritis of the knee and hip: factors predicting pain relief‐‐a systematic review. Seminars in Arthritis & Rheumatism 2013;42:451‐73.

Ivanov 1981 {published data only}

Ivanov B A, Koliago S A. Use of hydrocortisone in treating arthrosis deformans of the extremities. Voenno‐Meditsinskii Zhurnal 1981, (6):56‐7.

Jarner 1992 {published data only}

Jarner D, Aaboe T, Andersen L A. Intra‐articular indomethacin versus triamcinolone hexacetonide injections in osteoarthritis and hydrarthrosis. Scandinavian Journal of Rheumatology. Supplement 1992;93:67.

Jones 1993 {published data only}

Jones A, Regan M, Ledingham J, Pattrick M, Manhire A, Doherty M. Importance of placement of intra‐articular steroid injections. BMJ 1993;307:1329‐30.

Jones 2014 {published data only}

Jones T, Kelsberg G, Safranek S. FPIN's clinical inquiries: Intra‐articular corticosteroid injections for osteoarthritis of the knee. American Family Physician 2014;90:115‐6.

Keagy 1967 {published data only}

Keagy R D, Keim H A. Intra‐articular steroid therapy: repeated use in patients with chronic arthritis. American Journal of the Medical Sciences 1967;253:45‐51.

Khitrov 1997 {published data only}

Khitrov N A, Sil'vestrov V P, Tsurko V V. A comparative evaluation of local therapy methods in treating osteoarthrosis deformans. Terapevticheskii Arkhiv 1997;69:53‐4.

Kizilkaya 2004 {published data only}

Kizilkaya M, Yildirim O S, Dogan N, Kursad H, Okur A. Analgesic effects of intraarticular sufentanil and sufentanil plus methylprednisolone after arthroscopic knee surgery. Anesthesia and Analgesia 2004;98(4):1062‐5.

Kizilkaya 2005 {published data only}

Kizilkaya M, Yildirim O S, Ezirmik N, Kursad H, Karsan O. Comparisons of analgesic effects of different doses of morphine and morphine plus methylprednisolone after knee surgery. European Journal of Anaesthesiology 2005;22(8):603‐8.

Koyonos 2009 {published data only}

Koyonos L, Yanke A B, McNickle A G, Kirk S S, Kang R W, Lewis P B, et al. A randomized, prospective, double‐blind study to investigate the effectiveness of adding DepoMedrol to a local anesthetic injection in postmeniscectomy patients with osteoarthritis of the knee. American Journal of Sports Medicine 2009;37(6):1077‐82.

Krause 1971 {published data only}

Krause W. Intra‐articular steroid therapy in knee joint diseases. Medizinische Welt 1971;46:1841‐5.

Legre‐Boyer 2015 {published data only}

Legre‐Boyer V. Viscosupplementation: Techniques, indications, results.. Orthop Traumatol Surg Res 2015;9:S101‐108.

Lequesne 1970 {published data only}

Lequesne M, Bensasson M, Kemmer C, Amouroux J. Painful juxtameniscal areas in certain arthropathies of the knee and their treatment by juxtameniscal cortisone infiltration. Annals of the Rheumatic Diseases 1970;29:689.

Maricar 2013 {published data only}

Maricar N, Parkes M J, Callaghan M J, Felson D T, O'Neill T W. A systematic review of where and how to inject in the knee?. Osteoarthritis and Cartilage 2013;21:S300.

Maricar 2013c {published data only}

Maricar N, Callaghan M J, Felson D T, O'Neill T W. Predictors of response to intra‐articular steroid injections in knee osteoarthritis‐a systematic review. Rheumatology (United Kingdom) 2013;52:1022‐32.

Maricar 2014 {published data only}

Maricar N, Parkes M J, Forsythe L M, Felson D T, O'Neill T W. Do psychological factors predict response to intraarticular steroid therapy in knee osteoarthritis?. Osteoarthritis and Cartilage 2014;22:S381.

McAlindon 2014 {published data only}

McAlindon T E, Bannuru R R, Sullivan M C, Arden N K, Berenbaum F, Bierma‐Zeinstra S M, et al. OARSI guidelines for the non‐surgical management of knee osteoarthritis. Osteoarthritis and Cartilage 2014;22:363‐88.

Murdoch 1959 {published data only}

Murdoch W R, Will G. Prednisolone trimethylacetate in intra‐articular therapy. British Medical Journal 1959;1:1267‐70.

Murdoch 1959a {published data only}

Murdoch W R, Will G. Synovial fluid changes in intra‐articular therapy: effect of prednisolone trimethylacetate. British Medical Journal 1959;1:1271‐4.

Neame 2003 {published data only}

Neame R L, Doherty M. Managing osteoarthritis. Practitioner 2003;247:768‐70, 773, 775.

Nicol 1972 {published data only}

Nicol W J, Sarkin T L. Indications for intra‐articular steroid in osteo‐arthritis of the knee. South African Medical Journal. Suid‐Afrikaanse Tydskrif Vir Geneeskunde 1972;46:379.

No named author {published data only}

Steroid injections effective for knee osteoarthritis. Journal of Family Practice 2004;53:606.

No named author a {published data only}

Intraarticular injections in gonarthrosis [Intraartikulare injektionen bei gonarthrose]. Pharma‐Kritik 2006;28:1‐2.

No named author b {published data only}

Intra‐articular injections for osteoarthritis of the knee. Medical Letter on Drugs and Therapeutics 2006;48:25‐7.

No named author c {published data only}

Corticosteroids for knee OA. Pharmaceutical Journal 2004;272:465.

Parmigiani 2010 {published data only}

Parmigiani L, Furtado R N V, Lopes R V, Ribeiro L H C, Natour J. Joint lavage associated with triamcinolone hexacetonide injection in knee osteoarthritis: A randomized double‐blind controlled study. Clinical Rheumatology 2010;29:1311‐5.

Pendleton 2008 {published data only}

Pendleton A, Millar A, O'Kane D, Wright G D, Taggart A J. Can sonography be used to predict the response to intra‐articular corticosteroid injection in primary osteoarthritis of the knee?. Scandinavian Journal of Rheumatology 2008;37:395‐7.

Punzi 2001 {published data only}

Punzi L. Intra‐articular sodium hyaluronate reduces pain and improves function in osteoarthritis of knee. Clinical and Experimental Rheumatology 2001;19:9‐10.

Rasmussen 1998 {published data only}

Rasmussen S, Larsen A S, Thomsen S T, Kehlet H. Intraarticular glucocorticoid reduces pain, inflammatory response and convalescence after arthroscopic meniscectomy [abstract]. Acta Orthopaedica Scandinavica 1998;69(Suppl 282):53‐4.

Rasmussen 1998a {published data only}

Rasmussen S, Larsen A S, Thomsen S T, Kehlet H. Intraarticular glucocorticoid, morphine and bupivacaine reduces pain, inflammatory response and convalescence after arthroscopic meniscectomy [abstract]. Acta Orthopaedica Scandinavica 1998;69(Suppl 280):45.

Rasmussen 1998b {published data only}

Rasmussen S, Larsen A S, Thomsen S T, Kehlet H. Intra‐articular glucocorticoid, bupivacaine and morphine reduces pain, inflammatory response and convalescence after arthroscopic meniscectomy [abstract]. Pain 1998;78:131‐4.

Reshetov 2000 {published data only}

Reshetov P P, Tverdokhleb I P, Bezmenov V A. The use of hydrocortisone combined with ultrasound with gonarthrosis patients. Voprosy Kurortologii, Fizioterapii, i Lechebnoi Fizicheskoi Kultury 2000, (4):47‐8.

Ronchetti 2001 {published data only}

Ronchetti I P, Guerra D, Taparelli F, Boraldi F, Bergamini G, Mori G, et al. Morphological analysis of knee synovial membrane biopsies from a randomized controlled clinical study comparing the effects of sodium hyaluronate (Hyalgan) and methylprednisolone acetate (Depomedrol) in osteoarthritis. Rheumatology 2001;40:158‐69.

Roskos 2005 {published data only}

Roskos S E. Intra‐articular corticosteroid for treating osteoarthritis of the knee. American Family Physician 2005;72:1222‐3.

Saito 1971 {published data only}

Saito H, Asai H, Nakamura R. Effect of intra‐articular injection of steroid in deforming arthrosis of the knee. Seikei Geka ‐ Orthopedic Surgery 1971;22:612‐4.

Shah 1967 {published data only}

Shah K D, Wright V. Intra‐articular hydrocortisone in osteo‐arthrosis. Annals of the Rheumatic Diseases 1967;26:316‐8.

Sheldon 1973 {published data only}

Sheldon P, Beer T C. Synovitis of the knee treated by intra‐articular hydrocortisone acetate, hydrocortisone acetate plus saline, or saline alone. A double‐blind trial. Rheumatology and Rehabilitation 1973;12:37‐41.

Stein 1996 {published data only}

Stein A, Helmke K, Szopko C, Stein C, Yassouridis A. Intraarticular morphine versus steroid application in gonarthrosis and arthritis in case of acute painful joint [Intraartikulare morphin ‐ versus steroidapplikation bei gonarthrose und arthritis im akut schmerzhaften gelenk]. Deutsche Medizinische Wochenschrift 1996;121:255.

Stitik 2006 {published data only}

Stitik T P, Kumar A, Foye P M. Corticosteroid injections for osteoarthritis. American Journal of Physical Medicine & Rehabilitation 2006;85:S51‐65; quiz S66.

Stojanovic 1969 {published data only}

Stojanovic I, Spasojevic L, Koturovic L, Josipovic D. Our results in treatment of gonarthrosis. Reumatizam 1969;16:65‐9.

Talke 1986 {published data only}

Talke M. Intra‐articular corticoid therapy with triamcinolone hexacetonide. Fortschritte der Medizin 1986;104:742‐4.

Van Middelkoop 2013 {published data only}

Van Middelkoop M, Dziedzic K S, Doherty M, Zhang W, Bijlsma J W, McAlindon T E, et al. Individual patient data meta‐analysis of trials investigating the effectiveness of intra‐articular glucocorticoid injections in patients with knee or hip osteoarthritis: an OA Trial Bank protocol for a systematic review. Systems Review 2013;2:54.

Van Middelkoop 2013a {published data only}

Van Middelkoop M, Dziedzic K, Doherty M, Zhang W, Bijlsma J W, McAlindon T, et al. The OA trial bank: Individual patient data meta‐analysis of trials investigating the effectiveness of intra‐articular corticosteroid injections in patients with knee or hip oa. Annals of the Rheumatic Diseases. 2013; Vol. 72.

Van Middelkoop 2013b {published data only}

Van Middelkoop M, Dziedzic K, Doherty M, Zhang W, Bijlsma J, McAlindon T, et al. The oa trial bank: Individual patient data meta‐analysis of trials investigating the effectiveness of intra‐articular corticosteroid injections in patients with knee or hip oa. Osteoarthritis and Cartilage 2013;21:S259.

Van Middelkoop 2014 {published data only}

Van Middelkoop M, Arden N, Atchia I, Birrell F, Chao J, Lambert R, et al. The OA trial bank: Meta‐analysis of individual patient data show that patients with severe pain or with inflammatory signs detected by ultrasound especially benefit from intra‐articular glucocorticoids for knee or hip OA. Annals of the Rheumatic Diseases 2014;73:749.

Van Middelkoop 2014a {published data only}

Van Middelkoop M, Arden N, Atchia I, Birrell F, Chao J, Lambert R G, et al. The OA trial bank: Meta‐analysis of individual patient data show that patients with severe pain or with inflammatory signs detected by ultrasound especially benefit from intra‐articular glucocorticoids for knee or hip OA. Osteoarthritis and Cartilage 2014;22:S474‐5.

Wang 1998 {published data only}

Wang J J, Ho S T, Lee S C, Tang J J S, Liaw W J. Intraarticular triamcinolone acetonide for pain control after arthroscopic knee surgery. Anesthesia and Analgesia 1998;87(5):1113‐6.

Wang 2015 {published data only}

Wang F, He X. Intra‐articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: A meta‐analysis. Experimental and Therapeutic Medicine 2015;9:493‐500.

Wramner 1959 {published data only}

Wramner T. The effect of intra‐articular hydrocortisone therapy upon the joint temperature in osteoarthritis and rheumatoid arthritis. Acta Rheumatologica Scandinavica 1959;5:59‐65.

Yamamoto 1970 {published data only}

Yamamoto M, Fukuma H. Intra‐articular injection of adrenocortical steroid hormone in osteoarthritis of the knee. Seikei Geka ‐ Orthopedic Surgery 1970;21:103‐6.

Zhang 2008 {published data only}

Zhang W, Moskowitz R W, Nuki G, Abramson S, Altman R D, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence‐based, expert consensus guidelines. Osteoarthritis and Cartilage 2008;16:137‐62.

Zhang 2010 {published data only}

Zhang W, Nuki G, Moskowitz R W, Abramson S, Altman R D, Arden N K, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010;18:476‐99.

Zuckner 1958 {published data only}

Zuckner J, Machek O. Intra‐articular injections of hydrocortisone, prednisolone, and their tertiary‐butylacetate derivatives in patients with rheumatoid arthritis and osteoarthritis. Journal of Chronic Diseases 1958;8:637‐44.

References to studies awaiting assessment

Ellis 2011 {published data only}

Ellis M E, Lun V M Y, Preston Wiley J. Combination treatment for knee osteoarthritis. Clinical Journal of Sport Medicine 2011;21(4):374‐5.

Friedman 1978 {published data only}

Friedman D M, Moore M F. The efficacy of intraarticular corticosteroid for osteoarthritis of the knee. Arthritis and Rheumatism 1978;21:556.

Hall 2013 {published data only}

Hall M, Courtney P, Doherty S, Latief K, Zhang W, Doherty M. Ultrasound response following intra‐articular corticosteroid and a placebo injection in symptomatic osteoarthritic knees: A pilot study. Annals of the Rheumatic Diseases 2013;72:54.

Hall 2014 {published data only}

Hall M, Doherty S, Courtney P, Latief K, Zhang W, Doherty M. Ultrasound detected synovial change and pain response following intra‐articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: A pilot study. Annals of the Rheumatic Diseases 2014;73:1590‐1.

Motyl 2013 {published data only}

Motyl J M, Driban J B, McAdams E, McAlindon T E. Reliability and sensitivity of the 20‐meter walk test among patients with knee osteoarthritis. Osteoarthritis and Cartilage 2013;21:S137.

Motyl 2013a {published data only}

Motyl J M, Driban J B, McAdams E, Price L L, McAlindon T E. Test‐retest reliability and sensitivity of the 20‐meter walk test among patients with knee osteoarthritis. BMC Musculoskeletal Disorders 2013;14:166.

O'Neill 2014 {published data only}

O'Neill T W, Parkes M J, Maricar N, Gait A D, Cootes T F, Marjanovic E J, et al. Bone marrow lesions may not respond to anti‐inflammatory treatments in knee osteoarthritis (OA). Osteoarthritis and Cartilage 2014;22:S475.

Raynauld 1999 {published data only}

Raynauld J P. Clinical trials: Impact of intraarticular steroid injections on the progression of knee osteoarthritis. Osteoarthritis and Cartilage 1999;7:348‐9.

Rezende 2012 {published data only}

Rezende M U, Campos G C, Pailo A F, Frucchi R, Pasqualim T. Evaluation of the effect of adding corticosteroid to viscosupplementation: A prospective and randomized study. Osteoporosis International 2012;23:S132‐3.

Singh 1996 {published data only}

Singh G K, Jain S, Das S K, Sharma V. Conservative treatment of osteoarthritis (OA) of the knee vs add on intra‐articular (IA) steroid injection [abstract]. Journal of Clinical Epidemiology 1996;49 Suppl 1:8s.

Altman 1996

Altman R, Brandt K, Hochberg M, Moskowitz R, Bellamy N, Bloch DA, et al. Design and conduct of clinical trials in patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Results from a workshop. Osteoarthritis and Cartilage 1996;4(4):217‐43.

Bellamy 1995

Bellamy N. Outcome measurement in osteoarthritis clinical trials. The Journal of Rheumatology. Supplement 1995;43:49‐51.

Brandt 1996

Brandt KD. Diagnosis and Nonsurgical Management of Osteoarthritis. 1st Edition. Caddo, OK: Professional Communications, Inc., 1996.

Brandt 2001

Brandt K D. Management of osteoarthritis. In: Ruddy S, Harris E D, Sledge C B editor(s). Kelley’s Textbook of Rheumatology. 6th Edition. Philadelphia: W. B. Saunders Company, 2001:1419–32.

Clegg 2006

Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. The New England Journal of Medicine 2006;354(8):795‐808.

Cohen 1988

Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd Edition. Hillsdale, NJ: Lawrence Earlbaum Associates, 1988.

Creamer 1997

Creamer P. Intra‐articular corticosteroid injections in osteoarthritis: do they work and if so, how?. Annals of the Rheumatic Diseases 1997;56(11):634–6.

da Costa 2012

da Costa B R, Nüesch E, Reichenbach S, Jüni P, Rutjes A W S. Doxycycline for osteoarthritis of the knee or hip. Cochrane Database of Systematic Reviews 2012, Issue 11. [DOI: 10.1002/14651858.CD007323.pub3]

da Costa 2012a

da Costa BR, Rutjes AWS, Johnston BC, Reichenbach S, Nüesch E, Tonia T, et al. Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta‐epidemiological study. International Journal of Epidemiology 2012;41(5):1445‐59.

da Costa 2013

da Costa BR, Nüesch E, Rutjes AW, Johnston BC, Reichenbach S, Trelle S, et al. Combining follow‐up and change data is valid in meta‐analyses of continuous outcomes: a meta‐epidemiological study. Journal of Clinical Epidemiology 2013;66(8):847‐55.

da Costa 2014

da Costa BR, Nüesch E, Kasteler R, Husni E, Welch V, Rutjes AW, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database of Systematic Reviews 2014, Issue 9. [DOI: 10.1002/14651858.CD003115.pub4]

da Costa 2014a

da Costa BR, Jüni P. Systematic reviews and meta‐analyses of randomized trials: principles and pitfalls. European Heart Journal 2014;35:3336‐45.

DerSimonian 1986

DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88.

Dickersin 1994

Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994;309(6964):1286‐91.

Dworkin 2008

Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9:105‐21.

Dworkin 2009

Dworkin RH, Turk DC, McDermott MP, Peirce‐Sandner S, Burke LB, Cowan P, et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain 2009;146:238‐44.

Egger 1997

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315(7109):629‐34.

Egger 2001

Egger M, Smith GD. Principles of and procedures for systematic reviews. In: Egger M, Smith GD, Altman DG editor(s). Systematic Reviews in Health Care: Meta‐Analysis in Context. London: BMJ Books, 2001:23‐42.

Egger 2003

Egger M, Jüni P, Bartlett C, Holenstein F, Sterne J. How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technology Assessment (Winchester, England) 2003;7(1):1‐76.

Felson 2000

Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JA, et al. Osteoarthritis: New insights. Part 1: The disease and its risk factors (NIH Conference). Annals of Internal Medicine 2000;133(8):635–46.

Felson 2000a

Felson DT, Lawrence RC, Hochberg MC, McAlindon T, Minor MA, Blair SN, et al. Osteoarthritis: New insights. Part 2: Treatment approaches (NIH Conference). Annals of Internal Medicine 2000;133(9):726–37.

Guyatt 2008

Guyatt G, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924‐6.

Gøtzsche 2007

Gøtzsche PC, Hróbjartsson A, Maric K, Tendal B. Data extraction errors in meta‐analyses that use standardized mean differences. JAMA 2007;298(4):430‐7.

Higgins 2003

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60.

Higgins 2011

Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:1‐9.

Hochberg 2012

Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al. American College of Rheumatology 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care and Research 2012;64(4):465‐74.

Jüni 2001

Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2001;323(7303):42‐6.

Jüni 2006

Jüni P, Reichenbach S, Dieppe P. Osteoarthritis: rational approach to treating the individual. Best Practice & Research. Clinical Rheumatology 2006;20(4):721‐40.

Lefebvre 2008

Lefebvre C, Eisinga A, McDonald S, Paul N. Enhancing access to reports of randomized trials published world‐wide‐‐the contribution of EMBASE records to the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library. Emerging Themes in Epidemiology 2008;5(13):1‐13.

McColl 2000

McColl GJ, Dolezal H, Eizenberg N. Common corticosteroid injections. An anatomical and evidence based review. Australian Family Physician 2000;29:922‐6.

Nüesch 2009

Nüesch E, Trelle S, Reichenbach S, Rutjes AWS, Bürgi E, Scherer M, et al. The effects of the exclusion of patients from the analysis in randomised controlled trials: meta‐epidemiological study. BMJ 2009;339:b3244.

Nüesch 2010

Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta‐analyses of osteoarthritis trials: meta‐epidemiological study. BMJ 2010;341:c3515.

Nüesch 2013

Nüesch E, Häuser W, Bernardy K, Barth J, Jüni P. Comparative efficacy of pharmacological and non‐pharmacological interventions in fibromyalgia syndrome: network meta‐analysis. Annals of the Rheumatic Diseases 2013;72(6):955‐62.

Peters 2008

Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Contour‐enhanced meta‐analysis funnel plots help distinguish publication bias from other causes of asymmetry. Journal of Clinical Epidemiology 2008;61(10):991‐6.

Pham 2004

Pham T, van der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al. OMERACT‐OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis and Cartilage 2004;12(5):389‐99.

Reichenbach 2007

Reichenbach S, Sterchi R, Scherer M, Trelle S, Burgi E, Burgi U, et al. Meta‐analysis: chondroitin for osteoarthritis of the knee or hip. Annals of Internal Medicine 2007;146(8):580‐90.

Reichenbach 2010

Reichenbach S, Rutjes AW, Nüesch E, Trelle S, Jüni P. Joint lavage for osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2010, Issue 5. [DOI: 10.1002/14651858.CD007320.pub2]

RevMan 2014 [Computer program]

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Rozental 2000

Rozental TD, Sculco TP. Intra‐articular corticosteroids: an updated overview. American Journal of Orthopedics 2000;29(1):18‐23.

Rucker 2008

Rucker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I(2) in assessing heterogeneity may mislead. BMC Medical Research Methodology 2008;8(1):79.

Rutjes 2009

Rutjes AW, Nüesch E, Sterchi R, Kalichman L, Hendriks E, Osiri M, et al. Transcutaneous electrostimulation for osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD002823.pub2]

Rutjes 2009a

Rutjes AW, Nuesch E, Reichenbach S, Jüni P. S‐Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD007321.pub2]

Rutjes 2010

Rutjes AW, Nuesch E, Sterchi R, Jüni P. Therapeutic ultrasound for osteoarthritis of the knee or hip. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD003132.pub2]

Sterne 2001

Sterne JA, Egger M. Funnel plots for detecting bias in meta‐analysis: guidelines on choice of axis. Journal of Clinical Epidemiology 2001;54(10):1046‐55.

Sterne 2011

Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta‐analyses of randomised controlled trials. BMJ 2011;343:d4002.

Thompson 1999

Thompson SG, Sharp SJ. Explaining heterogeneity in meta‐analysis: a comparison of methods. Statistics in Medicine 1999;18(20):2693‐708.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Beyaz 2012

Methods

Randomised controlled trial

3‐arm parallel‐group design

Trial duration: 12 weeks

Participants

82 participants with knee osteoarthritis were randomised

73 participants were reported at baseline

Number of females: 59 of 73 (81%)

Mean age: 69.1 years

Interventions

Experimental intervention

40 mg triamcinolone acetonide (1 ml) plus 20 mg bupivacaine (4 ml), single intra‐articular injection

Control intervention

1 ml saline plus 20 mg bupivacaine (4 ml), single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC pain

Extracted function outcome: WOMAC function

Maximum follow‐up: 12 weeks

Notes

Funding: Boztepe State Hospital, Ordu, Republic of Turkey

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomized by the closed‐envelope technique into three groups". Because the "closed‐envelope technique" was not further specified, the risk of selection bias was considered unclear

Allocation concealment (selection bias)

Unclear risk

Quote: "Patients were randomized by the closed‐envelope technique into three groups". Because the "closed‐envelope technique" was not further specified, the risk of selection bias was considered unclear

Blinding of participants?

Low risk

Quote: "Since the solutions were in different colors, sticker was used to cover injectors to hide to ensure blinding."

Blinding of health care provider(s)

Low risk

Quote: "Injections were administered by another blinded investigator."

Intention‐to‐treat analysis performed? Pain

High risk

9 out of 82 participants were excluded because (quote) "they did not come for follow‐up"

Intention‐to‐treat analysis performed? Function

High risk

9 out of 82 participants were excluded because (quote) "they did not come for follow‐up"

Campos 2013

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 24 weeks

Participants

104 participants with knee osteoarthritis were randomised

104 participants were reported at baseline

Number of females: 79 out of 104 (76%)

Mean age: 63.0 years

Interventions

Experimental intervention

20 mg triamcinolone hexacetonide (1 ml) plus 6 ml hylan GF‐20, single intra‐articular injection

Control intervention

6 ml hylan GF‐20 intra‐articularly, single intra‐articular injection

Quote: "Patients with bilateral disease had both knees treated with the same drug, but only one knee (reported by the patient as the worst) was included in the study"

Outcomes

Extracted pain outcome: WOMAC Pain

Extracted function outcome: WOMAC Global

Maximum follow‐up: 24 weeks

Notes

Funding: São Paulo Research Foundation (FAPESP) (Sao Paulo, Brazil)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was performed by a computer‐generated program (available at: http://www.randomization.com/)."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Low risk

Quote: "Patients were blinded (blocked from watching the procedures by the use of a windscreen sunshade and did not know to which group they were assigned)."

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

High risk

5 of 52 participants excluded in experimental group, 6 of 52 participants excluded in control group

Intention‐to‐treat analysis performed? Function

High risk

5 of 52 participants excluded in experimental group, 6 of 52 participants excluded in control group

Castro 2007

Methods

Randomised controlled trial

5‐arm parallel‐group design

Trial duration: 12.9 months

Participants

150 participants with knee osteoarthritis were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: 115

Mean age: 65.4

Interventions

Experimental intervention

Triamcinolone acetonide (no dosage or unit specified) + joint lavage, single intra‐articular application

Control intervention

Joint lavage, single intra‐articular application

Outcomes

Extracted pain outcome: WOMAC Pain

Extracted function outcome: WOMAC Function

Maximum follow‐up: 12.9 months

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Low risk

All randomised participants included in the analysis

Cederlof 1966

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 8 weeks

Participants

51 injections in 44 knees belonging to 44 participants with knee osteoarthritis were randomised

Unclear number of participants reported at baseline

Number of females: 41 of 44 (93.2%)

Mean age: Not reported

Interventions

Experimental intervention

50 mg prednisolone acetate (2 ml), single intra‐articular injection

Control intervention

2 ml physiologic saline, single intra‐articular injection

Outcomes

Extracted pain outcome: Patient global assessment

Notes

Funding: Aktiebolaget Ferrosan, Malmö, Sweden

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The out‐patient department nurse decided which fluid was to be injected by tossing a coin"

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Unclear risk

Did not report extractable function outcome data

Chao 2010

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 12 weeks

Participants

79 participants with knee osteoarthritis were randomised

79 participants were reported at baseline

Number of females: 2 of 79 (2.5%)

Mean age: 64.3 years

Interventions

Experimental intervention

40 mg triamcinolone acetonide (1 ml), single intra‐articular injection

Control intervention

1 ml 0.9% saline, single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Pain

Extracted function outcome: WOMAC Global

Maximum follow‐up: 12 weeks

Notes

Funding: National Skeletal Muscle Research Center, NIH Grant HD050837

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Low risk

Quote: "Patients and assessors were blinded to treatment status" "Patients were then randomized to receive an injection of either (...) triamcinolone acetonide or (...) saline, which were drawn into a syringe covered with opaque tape prior to the patient encounter."

Blinding of health care provider(s)

High risk

Quote: "Injections were given (...) by a non‐blinded physician"

Intention‐to‐treat analysis performed? Pain

High risk

9 of 40 participants excluded in experimental group, 9 of 39 participants excluded in control group

Intention‐to‐treat analysis performed? Function

High risk

9 of 40 participants excluded in experimental group, 9 of 39 participants excluded in control group

Di Sante 2012

Methods

Randomised controlled trial

3‐arm parallel‐group design

Trial duration: 4 weeks

Participants

60 participants with knee osteoarthritis were randomised

60 participants were reported at baseline

Mean age: 70.6

Interventions

Experimental interventions

40 mg methylprednisolone acetate and lidocaine hydrochloride, single intra‐articular injection + Horizontal therapy* locally (10 times over 2 weeks, each lasting 30 minutes)

Control intervention

Horizontal therapy* locally (10 times over 2 weeks, each lasting 30 minutes)

Treatment duration: 4 weeks

*Horizontal therapy was described as (quote): "Placement of 4 cutaneous electrodal pads (8 x 13 cm), one in center of the popliteal, one on the patella and two others at the posterior proximal site of the thighs, with a stimulation frequency oscillating at 100 Hz between 4400 and 12346 Hz for 30 minutes"

Maximum follow‐up: 4 weeks

Outcomes

Extracted pain outcome: Pain overall

Extracted function outcome: WOMAC Function

Maximum follow‐up: 4 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "(...) using a computer generated 1:1:1 allocation sequence."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

High risk

No intra‐articular sham injection in the placebo group (local therapy only)

Blinding of health care provider(s)

High risk

No intra‐articular sham injection in the placebo group (local therapy only)

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Low risk

All randomised participants included in the analysis

Dieppe 1980

Methods

Randomised controlled trial

2‐arm cross‐over design

Trial duration: 2 weeks

Participants

24 knees belonging to 16 participants with knee osteoarthritis were randomised

24 knees belonging to 16 participants were reported at baseline

Mean age: 65

Number of females: 13 out of 16 (81%)

Interventions

Experimental intervention

20 mg triamcinalone hexacetonide (1 ml), single intra‐articular injection

Control intervention

1 ml of saline, single intra‐articular injection

Cross‐over after 1 week. Every participant received 1 injection (experimental and control) each

Outcomes

Extracted pain outcome: Pain overall

Maximum follow‐up: 1 week

Notes

2 trials were reported in the same paper. Trial A did not report pain outcomes seperately for treatment and intervention and was excluded. Trial B was included in the analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

High risk

Quote: Described as "single‐blind, blind‐observer", implying that participants were not blinded

Blinding of health care provider(s)

High risk

Quote: Described as "single‐blind, blind‐observer", implying that healthcare providers were not blinded

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Friedman 1980

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 8 weeks

Participants

34 participants with knee osteoarthritis were randomised

34 participants were reported at baseline

Number of females: Not reported

Mean age: 60.0 years

Interventions

Experimental intervention

20 mg triamcinolone hexacetonide, single intra‐articular injection

Control intervention

"Polysorbate, sorbitol solution, benzyl alcohol and water", single intra‐articular injection

Outcomes

Extracted pain outcome: Pain overall

Maximum follow‐up: 8 weeks

Notes

Funding: Grant from the Eastern Pennsylvania Chapter of the Arthritis Foundation and by the Philadelphia Foundation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not clearly reported, so the risk of selection bias was unclear. Quote: "Half of the patients, selected according to a predetermined random schedule, were treated (...)."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Low risk

Quote: "During the time of [the injection] (...), the physician and patient were positioned so that neither could see the nurse's face nor the material she injected. Thus, neither had any direct information concerning what was injected and, practically speaking, had no contact with the only person who knew"

Blinding of health care provider(s)

Low risk

Quote: "The physician‐experimenter performed the arthrocentesis (...) a nurse‐assistant entered the room and performed the injection through the intraarticular needle, and left the room. During the time of this taking place, the physician and patient were positioned so that neither could see the nurse's face nor the material she injected. Thus, neither had any direct information concerning what was injected and, practically speaking, had no contact with the only person who knew"

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis. Quote: "All patients were seen 1 wk, 4 wk, 6 wk and 8 wk post‐injection except those whose pain scores at any subsequent evaluation were the same as their pre‐treatment scores; they were not seen further. It was assumed that their scores would no longer improve and they were counted as remaining at their pre‐treatment level throughout the experiment".

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Frías 2004

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 12 weeks

Participants

299 knees belonging to 205 participants with knee osteoarthritis were randomised

299 knees belonging to 205 participants were reported at baseline

Number of females: 234 (78%) of 299 knees belonged to female participants

Mean age: 67.0 years

Interventions

Experimental intervention

40 mg triamcinolone acetonide plus lavage (3 L of cold (8°C) saline), single intra‐articular application

Control intervention

Lavage (3 L of cold (8°C) saline), single intra‐articular application

Outcomes

Extracted pain outcome: Pain overall

Maximum follow‐up: 12 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

Although the authors stated "Glucocorticoid treatment with triamcinolone acetonide was always given on a blind basis", they also stated that this was an open trial (Quote: "The study was of the longitudinal, open, prospective, controlled type").The risk of performance bias was therefore considered unclear

Blinding of health care provider(s)

Unclear risk

Although the authors stated "Glucocorticoid treatment with triamcinolone acetonide was always given on a blind basis", they also stated that this was an open trial (Quote: "The study was of the longitudinal, open, prospective, controlled type"). The risk of performance bias was therefore considered unclear

Intention‐to‐treat analysis performed? Pain

High risk

82 of 299 knees were excluded at 1 month, 51 of 299 knees were excluded at 3 months

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Gaffney 1995

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 6 weeks

Participants

84 participants with knee osteoarthritis were randomised

84 participants were reported at baseline

Number of females: 60 out of 84 (71%)

Mean age: 67.0 years

Interventions

Experimental intervention

20 mg triamcinolone hexacetonide (1 ml), single intra‐articular injection

Control intervention

1 ml of 0.9% normal saline, single intra‐articular injection

Outcomes

Extracted pain outcome: Pain overall

Extracted function outcome: Other function composite

Maximum follow‐up: 6 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Low risk

Quote: "Although this study was not, by strict definition, double‐blinded, we attempted to ensure that patients were not aware of the treatment allocated to them, by shielding the identity of the treatment received from their view at the time of injection; only the injecting physician (IL) was aware of the nature of the injection administered."

Blinding of health care provider(s)

High risk

Quote: "Although this study was not, by strict definition, double‐blinded, we attempted to ensure that patients were not aware of the treatment allocated to them, by shielding the identity of the treatment received from their view at the time of injection; only the injecting physician (IL) was aware of the nature of the injection administered."

Intention‐to‐treat analysis performed? Pain

Unclear risk

2 of 42 participants in control group withdrew. It was unclear whether all participants randomised were also analysed

Intention‐to‐treat analysis performed? Function

Unclear risk

2 of 42 participants in control group withdrew. It was unclear whether all participants randomised were also analysed

Grecomoro 1992

Methods

Randomised controlled trial

2‐arm cross‐over design

Trial duration: 8.6 weeks

Participants

40 participants with knee osteoarthritis were randomised

40 participants were reported at baseline

Number of females: 27 out of 40 (67.5%)

Mean age: 42.3 years

Interventions

Experimental intervention

0.4 mg dexamethasonephosphate plus 20 mg sodium hyaluronate in 2 ml phosphate buffer, 5 intra‐articular injections, 1 weekly for 5 weeks

Control intervention

20 mg sodium hyaluronate in 2 ml phosphate buffer, 5 intra‐articular injections, 1 weekly for 5 weeks

Outcomes

Extracted pain outcome: Pain on activities other than walking

Maximum follow‐up: 8.6 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

High risk

Quote: "The trial design was open and randomized."

Blinding of health care provider(s)

High risk

Quote: "The trial design was open and randomized."

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Henriksen 2015

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 26 weeks

Participants

100 participants with knee osteoarthritis were randomised

100 participants were reported at baseline

Number of females: 61 out of 100 (61%)

Mean age: 63.4 years

Interventions

Experimental intervention

40 mg methylprednisolone acetate (1 ml) dissolved in 4 ml of lidocaine hydrochloride, single intra‐articular injection + 12‐week exercise program

Control intervention

1 ml isotonic saline mixed with 4 ml of lidocaine hydrochloride, single intra‐articular injection + 12‐week exercise program

Outcomes

Extracted pain outcome: Other pain composite

Extracted pain function: Other function composite

Maximum follow‐up: 26 weeks

Notes

Funding: Grants by: 10‐093704 from the Danish Council for Independent Research Medical Science, Oak Foundation, Association of Danish Physiotherapists, Lundbeck Foundation, Capital Region of Denmark

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "A computer‐generated randomization sequence was produced before any patients were enrolled that allocated participants in permuted blocks of 2 to 6 to the corticosteroid or the placebo group (1:1)."

Allocation concealment (selection bias)

Low risk

Quote: "The randomization sequence was prepared by a biostatistician with no clinical involvement in the trial (R.C.). The allocation was concealed in a password‐protected computer file only accessible by the biostatistician. Individual allocations were held in sealed, opaque, consecutively numbered envelopes."

Blinding of participants?

Low risk

Quote: "To ensure blinding of the participants and the clinician performing the injections, the syringes were prepared by the study nurse in the absence of participants and blinded study staff. Because the corticosteroid liquid is milky white and the saline is clear, the syringes were masked with opaque tape to prevent disclosure of the content during the injection procedure."

Blinding of health care provider(s)

Low risk

Quote: "To ensure blinding of the participants and the clinician performing the injections, the syringes were prepared by the study nurse in the absence of participants and blinded study staff. Because the corticosteroid liquid is milky white and the saline is clear, the syringes were masked with opaque tape to prevent disclosure of the content during the injection procedure."

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Low risk

All randomised participants included in the analysis

Jones 1996

Methods

Randomised controlled trial

2‐arm cross‐over design

Trial duration: 16 weeks

Participants

59 participants with knee osteoarthritis were randomised

59 participants were reported at baseline

Number of females: 37 out of 59 (63%)

Mean age: 70.6 years

Interventions

Experimental intervention

40 mg methyl prednisolone acetate (1 ml), single intra‐articular injection

Control intervention

1 ml 0.9% saline, single intra‐articular injection

Cross‐over after 8 weeks. Every participant received 1 injection (experimental and control) each

Outcomes

Extracted pain outcome: Pain on activities other than walking

Maximum follow‐up: 8 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

Quote: "Each injection was given by a second operator, thus blinding both patient and assessor." No further description of blinding

Blinding of health care provider(s)

Unclear risk

Quote: "Each injection was given by a second operator, thus blinding both patient and assessor." No further description of blinding

Intention‐to‐treat analysis performed? Pain

High risk

Quotes: "As some data was missing due to patient withdrawal, all analyses were performed on a last measures carried forward, intention to treat basis", but still not all participants randomised were analysed. Quote: "One patient failed to enter the study and received no injection, leaving 59 patients available for the analysis."

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Lyons 2005

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 8.6 weeks

Participants

20 participants with knee osteoarthritis were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: 11

Mean age: 59.7

Interventions

Experimental intervention

80 mg methylprednisolone (2 ml) + 5 ml 1% lignocaine, single intra‐articular injection

Control intervention

10 ml of 1% lignocaine, single intra‐articular injection

Outcomes

Extracted pain outcome: Pain overall

Extracted function outcome: Global disability score

Maximum follow‐up: 8.6 weeks

Notes

Funding: West London Research Network, Primary Care Scientist Award funded by the Department of Health

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind healthcare providers was appropriate

Blinding of health care provider(s)

High risk

Quote: "(The study) was single blind, with the principal investigator administering the treatment and also measuring outcome."

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis

Intention‐to‐treat analysis performed? Function

Low risk

All randomised participants included in the analysis

Miller 1958

Methods

Randomised controlled trial

5‐arm parallel‐group design

Trial duration: 33.8 weeks

Participants

202 participants with knee osteoarthritis were randomised

Unclear number of participants reported at baseline

Number of females: 122

Mean age: not reported

Interventions

Experimental intervention

50 mg of hydrocortisone (2 ml) + 8 ml of physiological normal saline, 5 intra‐articular injections, interval of 2 weeks

Control intervention

Physiological normal saline solution (no dosage), 5 intra‐articular injections, interval of 2 weeks

Outcomes

Extracted pain outcome: Patients' global assessment

Maximum follow‐up: 25.8 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

High risk

21 of 202 participants were excluded

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

NCT00414427

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 12 weeks

Participants

79 participants with knee osteoarthritis were randomised

79 participants were reported at baseline

Number of females: 3 out of 79 (4%)

Mean age: 63.0 years

Interventions

Experimental intervention

40 mg triamcinolone acetonide, single intra‐articular injection

Control intervention

0.9% saline (no dosage), single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Pain

Maximum follow‐up: 12 weeks

Notes

Funding: University of California, San Diego

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

It was unclear if method used to blind healthcare providers was appropriate

Intention‐to‐treat analysis performed? Pain

High risk

7 of 40 participants excluded in experimental group, 5 of 39 participants excluded in control group

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Ozturk 2006

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 52 weeks

Participants

47 participants with knee osteoarthritis were randomised

40 participants were reported at baseline

Number of females: 39 out of 47 (83%)

Mean age: 58.0 years

Interventions

Experimental intervention

40 mg triamcinolone acetonide (1 ml) plus 2 ml sodium hyaluronate. Sodium hyaluronate was administered in 3 intra‐articular injections in the first month and 3 intra‐articular injections during the sixth month, triamcinolone acid was added prior to the first and fourth application.

Control intervention

2 ml sodium hyaluronate, 3 intra‐articular injections in the first month, and 3 intra‐articular injections during the sixth month

Outcomes

Extracted pain outcome: WOMAC Pain

Maximum follow‐up: 25.9 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients were assigned to one of the two treatment groups based on a table of randomly assorted digits: A and B."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if participants were blinded (trial described as "single blind" but no description of who was blinded)

Blinding of health care provider(s)

Unclear risk

It was unclear if healthcare providers were blinded (trial described as "single blind" but no description of who was blinded)

Intention‐to‐treat analysis performed? Pain

High risk

7 of 23 participants excluded in experimental group, 0 of 24 participants excluded in control group

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Petrella 2015

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 26 weeks

Participants

98 participants with knee osteoarthritis were randomised

98 participants were reported at baseline

Number of females: 56 out of 98 (57%)

Mean age: 59.7 years

Interventions

Experimental intervention

10 mg triamcinolone acetonide + hyaluronan solution (no dosage stated), 6 ml total, single intra‐articular injection

Control intervention

Hyaluronan solution (no dosage stated), single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Pain

Extracted function outcome: WOMAC Function

Maximum follow‐up: 26 weeks

Notes

Funding: Carbylan Therapeutics

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The randomization treatment was computer generated and was stratified by study center."

Allocation concealment (selection bias)

Unclear risk

Quote: "The randomization treatment was computer generated and was stratified by study center."

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

High risk

Quote: "An injecting physician delivered the randomized treatment and remained unblinded."

Intention‐to‐treat analysis performed? Pain

High risk

2 of 33 participants excluded in experimental group, 1 of 33 participants excluded in control group

Intention‐to‐treat analysis performed? Function

High risk

2 of 33 participants excluded in experimental group, 1 of 33 participants excluded in control group

Popov 1989

Methods

Randomised controlled trial

5‐arm parallel‐group design

Trial duration: 2.7 weeks

Participants

48 participants with knee osteoarthritis were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: 38

Mean age: 55 years

Interventions

Experimental interventions

Intervention (A): 40 mg triamcinolone, 3 intra‐articular injections, interval 1 week

Intervention (B): 50 mg hydrocortisone, 3 intra‐articular injections, interval 1 week

Control intervention

Saline solution (no dosage stated), 2 intra‐articular injections, interval 1 week

Outcomes

Extracted pain outcome: (A)‐(B): other algofunctional

Extracted function outcome: (A)‐(B): other algofunctional

Maximum follow‐up: 0.7 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

It was unclear if method used to blind healthcare providers was appropriate

Intention‐to‐treat analysis performed? Pain

Unclear risk

It was unclear whether all participants randomised were also analysed

Intention‐to‐treat analysis performed? Function

Unclear risk

It was unclear whether all participants randomised were also analysed

Ravaud 1999

Methods

Randomised controlled trial

2 x 2 factorial design

Trial duration: 24 weeks

Participants

98 participants with knee osteoarthritis were randomised

98 participants were reported at baseline

Number of females: 66 out of 98 (67%)

Mean age: 65.4

Interventions

Experimental interventions

Intervention (A): 3.75 mg cortivazol (1.5 ml), single intra‐articular injection

Intervention (B): Lavage, single intra‐articular application + 3.75 mg cortivazol (1.5 ml), single intra‐articular injection

Control intervention

Intervention (A): 1.5 ml 0.9% normal saline, single intra‐articular injection

Intervention (B): Lavage, single intra‐articular application

Outcomes

Extracted pain outcome: Pain overall

Extracted function outcome: Lequesne index

Maximum follow‐up: 24 weeks

Notes

Funding: Société Française de Rhumatologie and the Direction de la Recherche Clinique (Assistance Publique ‐ Hôpitaux de Paris)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

Quote: "The study was double‐blind in relation to the IA corticosteroid and open with regard to joint lavage."

Blinding of health care provider(s)

Unclear risk

Quote: "The study was double‐blind in relation to the IA corticosteroid and open with regard to joint lavage. However, the procedure (joint lavage and/or IA injection) was performed by a physician other than the blinded evaluator."

Intention‐to‐treat analysis performed? Pain

Low risk

All randomised participants included in the analysis. Quote: "The last observation–carried‐forward procedure was used to adjust for missing values."

Intention‐to‐treat analysis performed? Function

Low risk

All randomised participants included in the analysis. Quote: "The last observation–carried‐forward procedure was used to adjust for missing values."

Raynauld 2003

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 54 weeks

Participants

68 participants with knee osteoarthritis were randomised

68 participants were reported at baseline

Number of females: 42 out of 68 (68%)

Mean age: 63.2 years

Interventions

Experimental intervention

40 mg triamcinolone acetonide (1 ml), 8 intra‐articular injections, interval 3 months, over 21 months

Control intervention

1 ml saline intra‐articularly, 8 intra‐articular injections, interval 3 months, over 21 months

Outcomes

Extracted pain outcome: WOMAC Pain. After end of treatment (during follow‐up)

Extracted function outcome: WOMAC Function. After end of treatment (during follow‐up)

Maximum follow‐up: 12.9 weeks

Notes

Funding: Fonds de la recherche en santé du Québec

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients were randomly assigned to the IA steroid or IA saline group based on a table of randomly assorted digits."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

Study described as double‐blind but no description of method of blinding provided

Blinding of health care provider(s)

High risk

Study described as double‐blind. The following statements indicate that "double‐blind" in this trial means that only patients and outcome assessors were blinded: "In order to preserve the blind, the injections were given by a rheumatologist (DC or BH) other than the evaluators." "Investigators performed these evaluations in a blinded manner using validated measures."

Intention‐to‐treat analysis performed? Pain

High risk

1 of 34 participants excluded in experimental group, 1 of 34 participants excluded in control group

Intention‐to‐treat analysis performed? Function

High risk

1 of 34 participants excluded in experimental group, 1 of 34 participants excluded in control group

Schue 2011

Methods

Randomised controlled trial

3‐arm parallel‐group design

Trial duration: 8 weeks

Participants

16 participants with knee osteoarthritis were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: not reported

Mean age: not reported

Interventions

Experimental intervention

80 mg methylprednisolone, single intra‐articular injection

Control intervention

Saline (no dosage specified), single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Global

Maximum follow‐up: 8 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Unclear risk

It was unclear whether all participants randomised were also analysed

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

Smith 2003

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 24 weeks

Participants

77 participants with knee osteoarthritis were randomised

71 participants were reported at baseline

Number of females: 27 out of 77 (35%)

Mean age: 66.8 years

Interventions

Experimental intervention

120 mg methylprednisolone acetate following joint lavage, single intra‐articular injection

Control intervention

Treatment duration: 1 day

Normal saline (no dosage) following joint lavage, single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Pain

Extracted function outcome: WOMAC Function

Maximum follow‐up: 24 weeks

Notes

Funding: National Health and Medical Research Council (Australia) Arthritis Foundation of Australia

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was computer‐generated by a member of the hospital pharmacy department, who also prepared a blinded intra‐articular injection"

Allocation concealment (selection bias)

Low risk

Quote: "Randomization was computer‐generated by a member of the hospital pharmacy department, who also prepared a blinded intra‐articular injection"

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

It was unclear if method used to blind healthcare providers was appropriate

Intention‐to‐treat analysis performed? Pain

High risk

Quote: "In the event of relapse as defined above, the last documented outcome variables were carried forward". Still, 6 participants were excluded (those needing surgical intervention because of the arthroscopic findings at baseline)

Intention‐to‐treat analysis performed? Function

High risk

Quote: "In the event of relapse as defined above, the last documented outcome variables were carried forward". Still, 6 participants were excluded (those needing surgical intervention because of the arthroscopic findings at baseline)

Wright 1960

Methods

Randomised controlled trial

3‐arm parallel‐group design

Trial duration: 20 weeks

Participants

38 knees belonging to 25 participants with knee osteoarthritis were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: not stated

Mean age: not stated

Interventions

Experimental intervention

Intervention (A): 25 mg hydrocortisone acetate (1 ml), 4 intra‐articular injections, interval 2 weeks over 6 weeks

Intervention (B): 25 mg hydrocortisone tertiary‐butylacetate (1 ml), 4 intra‐articular injections, interval 2 weeks over 6 weeks

Control intervention

1 ml of placebo, 4 intra‐articular injections, interval 2 weeks over 6 weeks

Cross‐over design, every participant received 3 x 4 injections

Outcomes

Only information on adverse events was extracted

Notes

There was no extractable data on pain or function

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The order of courses in each patient was randomized from a master sheet in which names were entered consecutively."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Unclear risk

Did not report extractable pain outcome data

Intention‐to‐treat analysis performed? Function

Unclear risk

Did not report extractable function outcome data excluded in control group

Yavuz 2012

Methods

Randomised controlled trial

4‐arm parallel‐group design

Trial duration: 12 weeks

Participants

120 participants with knee osteoarthritis were randomised

120 participants were reported at baseline

Number of females: 76 out of 120 (63%)

Mean age: 60.0 years

Interventions

Experimental intervention

Intervention (A): 40 mg triamsinolon acetonate (1 ml), single intra‐articular injection

Intervention (B): 3 mg betametazone disodium phosphate (1 ml), single intra‐articular injection

Intervention (C): 40 mg methylprednisolone acetate (1 ml), single intra‐articular injection

Control intervention

1 ml 0.9% sodium chloride, single intra‐articular injection

Outcomes

Extracted pain outcome (A)‐(C): Pain overall

Extracted function outcome (A)‐(C): Lequesne index

Maximum follow‐up: 12 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "A total of 120 eligible patients with knee osteoarthritis were included (according to their admission date) and randomized into four groups."

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if participants were blinded

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Unclear risk

It was unclear whether all participants randomised were also analysed

Intention‐to‐treat analysis performed? Function

Unclear risk

It was unclear whether all participants randomised were also analysed

Young 2001

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 4.3 weeks

Participants

41 knees belonging to 40 participants with knee osteoarthritis were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: 16

Mean age: 66.5 years

Interventions

Experimental intervention

120 mg methylprednisolone acetate, single intra‐articular injection

Control intervention

Normal saline (no dosage stated), single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Global

Extracted function outcome: Other function composite

Maximum follow‐up: 4.3 weeks

Notes

Funding: National Health and Medical Research Council, The Clive and Vera Ramaciotti Trust, The Rebecca L. Cooper Foundation, University of New South Wales, The Arthritis Foundation of Australia, The Royal Australasian College of Physicians

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method used to generate random sequence of allocation was not reported, so the risk of selection bias was unclear

Allocation concealment (selection bias)

Unclear risk

Method used to conceal the random sequence of allocation was not reported, so the risk of selection bias was unclear

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Unclear risk

It was unclear whether all participants randomised were also analysed

Intention‐to‐treat analysis performed? Function

Unclear risk

It was unclear whether all participants randomised were also analysed

Zhilyayev 2012

Methods

Randomised controlled trial

4‐arm parallel‐group design

Trial duration: 12 weeks

Participants

209 knees belonging to 112 participants were randomised

Unclear number of participants with knee osteoarthritis reported at baseline

Number of females: not stated

Mean age: not stated

Interventions

Experimental intervention

20 mg triamcinolone acetonid plus 10 ml 0.5% procaine, single intra‐articular injection

Control intervention

10 ml 0.5% procaine, single intra‐articular injection

Outcomes

Extracted pain outcome: WOMAC Pain

Maximum follow‐up: 12 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "joints were randomized by envelopes to one of 4 treatments"

Allocation concealment (selection bias)

Unclear risk

Quote: "joints were randomized by envelopes to one of 4 treatments"

Blinding of participants?

Unclear risk

It was unclear if method used to blind participants was appropriate

Blinding of health care provider(s)

Unclear risk

Physicians were not explicitly described as blinded, so the risk of performance bias was unclear

Intention‐to‐treat analysis performed? Pain

Unclear risk

It was unclear whether all participants randomised were also analysed

Intention‐to‐treat analysis performed? Function

Unclear risk

Not applicable, no function outcome reported

IA: intra‐articular
WOMAC: Western Ontario and McMaster Universities Arthritis Index

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Abdulla 2013

Recent systematic review

Anonymous 1978

Wrong study design

Anonymous 2011

Wrong study design

Arroll 2004

Recent systematic review

Arroll 2005

Wrong study design

Avouac 2010

Recent systematic review

Baker 1969

Active comparator

Bannuru 2013

Wrong study design: Abstract to relevant systematic review, no references listed

Bannuru 2014

Wrong study design: Abstract to relevant systematic review, no references listed

Bannuru 2015

Recent systematic review

Baratham 2010

Wrong outcomes

Bellamy 2005

Recent systematic review

Bellamy 2006

Recent systematic review

Bennell 2012

Wrong study design

Bjordal 2007

Recent systematic review

Blanke 2008

Wrong study design

Bourne 1985

Wrong study design

Brys 2004

Wrong study design

Canillas 2011

Wrong study design

Cats 1979b

Wrong study population

Charalambous 2004

Wrong study design

Cheng 2012

Recent systematic review

Courtney 2009

Wrong study design

Douglas 2012

Wrong study design

Gait 2014

Wrong study design

Garg 2013

Wrong study design: Abstract to relevant systematic review
, no references listed

Garg 2014

Reason for exclusion

Gerlag 2008a

Wrong study design

Godwin 2004

Recent systematic review

Habib 2009

Wrong study design

Habib 2010

Wrong study design

Hepper 2009

Reason for exclusion

Hirsch 2013

Reason for exclusion

Ivanov 1981

Wrong comparator

Jarner 1992

Active comparator

Jones 1993

Wrong study design

Jones 2014

Wrong study design

Keagy 1967

Wrong study design

Khitrov 1997

Active comparator

Kizilkaya 2004

Postsurgical setting

Kizilkaya 2005

Postsurgical setting

Koyonos 2009

Postsurgical setting

Krause 1971

Wrong study design

Legre‐Boyer 2015

Wrong study design

Lequesne 1970

Wrong study design

Maricar 2013

Wrong study design: Abstract to relevant systematic review
, no references listed

Maricar 2013c

Recent systematic review

Maricar 2014

Wrong study design

McAlindon 2014

Wrong study design

Murdoch 1959

Wrong study design

Murdoch 1959a

Wrong study design

Neame 2003

Wrong study design

Nicol 1972

Wrong study design

No named author

Wrong study design

No named author a

Wrong study design

No named author b

Wrong study design

No named author c

Wrong study design

Parmigiani 2010

Duplicate reference

Pendleton 2008

Wrong study design

Punzi 2001

Wrong intervention

Rasmussen 1998

Postsurgical setting

Rasmussen 1998a

Postsurgical setting

Rasmussen 1998b

Postsurgical setting

Reshetov 2000

Wrong comparator

Ronchetti 2001

Active comparator

Roskos 2005

Wrong study design

Saito 1971

Wrong study design

Shah 1967

Wrong comparator

Sheldon 1973

Wrong study population

Stein 1996

Active comparator

Stitik 2006

Wrong study design

Stojanovic 1969

Wrong study design

Talke 1986

Wrong study design

Van Middelkoop 2013

Wrong study design: Abstract to relevant systematic review
, no references listed

Van Middelkoop 2013a

Wrong study design: Abstract to relevant systematic review
, no references listed

Van Middelkoop 2013b

Wrong study design

Van Middelkoop 2014

Wrong study design: Abstract to relevant systematic review
, no references listed

Van Middelkoop 2014a

Wrong study design: Abstract to relevant systematic review
, no references listed

Wang 1998

Postsurgical setting

Wang 2015

Wrong study design

Wramner 1959

Wrong study design

Yamamoto 1970

Wrong study design

Zhang 2008

Wrong study design

Zhang 2010

Wrong study design

Zuckner 1958

Active comparator

Characteristics of studies awaiting assessment [ordered by study ID]

Ellis 2011

Methods

Randomised controlled trial

2‐arm parallel‐group design

Trial duration: 12 weeks

Participants

16 participants with knee osteoarthritis were randomised

Interventions

Experimental intervention

3‐month exercise program plus 40 mg triamcinolone mixed with 4 ml 1% lidocaine, single intra‐articular injection

Control intervention

3‐month exercise program plus 1 ml normal saline mixed with 4 ml 1% lidocaine, single intra‐articular injection

Outcomes

Maximum follow‐up: 12 weeks

Outcome data (KOOS pain and function, WOMAC pain and function) not extractable

Notes

Friedman 1978

Methods

Unclear

Participants

Unclear

Interventions

Unclear

Outcomes

Outcome data not extractable

Notes

Hall 2013

Methods

Randomised controlled trial

2‐arm parallel‐group design

Participants

25 participants with knee osteoarthritis were randomised

Interventions

Experimental intervention

40 mg methylprednisolone acetate, single intra‐articular injection

Control intervention

saline, single intra‐articular injection

Cross‐over design: Every participant received 1 injection each

Outcomes

Maximum follow‐up: 1 week

Outcome data (WOMAC pain, pain overall, ICOAP questionnaire, ultrasound examination) not extractable

Notes

Hall 2014

Methods

Randomised controlled trial

2‐arm parallel‐group design

Participants

25 participants with knee osteoarthritis were randomised

Interventions

Experimental intervention

40 mg methylprednisolone acetate, single intra‐articular injection

Control intervention

saline, single intra‐articular injection

Cross‐over design: Every participant received 1 injection each

Outcomes

Maximum follow‐up: 1 week

Outcome data (WOMAC pain, pain overall, ICOAP questionnaire, ultrasound examination) not extractable

Notes

Motyl 2013

Methods

Measurement reliability study on participants later taking part in a randomised controlled trial for intra‐articular corticosteroid injection in knee osteoarthritis

Participants

15 participants with knee osteoarthritis

Interventions

Unclear

Data for the study was collected before the intra‐articular injection

Outcomes

Outcome data not extractable

Notes

Motyl 2013a

Methods

Measurement reliability study on participants later taking part in a randomised controlled trial for intra‐articular corticosteroid injection in knee osteoarthritis

Participants

15 participants with knee osteoarthritis

Interventions

Unclear

Data for the study was collected before the intra‐articular injection

Outcomes

Outcome data not extractable

Notes

O'Neill 2014

Methods

Open‐label clinical trial

Participants

100 participants with knee osteoarthritis

Interventions

Experimental intervention

Corticosteroid, single intra‐articular injection, type and dosage of corticosteroid unclear.

The study analysed the changes in MRI scans before and after the intra‐articular corticosteroid injection. All participants received the experimental intervention, there was no control group.

Outcomes

Outcome data not extractable

Notes

Raynauld 1999

Methods

Randomised controlled trial

2‐arm parallel‐group design

Participants

80 participants with knee osteoarthritis were randomised

Interventions

Experimental intervention

40 mg triamcinolone hexacetonide, 8 intra‐articular injections, 3 months interval

Control intervention

Placebo, 8 intra‐articular injections, 3 months interval

Outcomes

Outcome data (pain overall, WOMAC) not extractable

Notes

Rezende 2012

Methods

Randomised controlled trial

2‐arm parallel‐group design

Participants

104 participants with knee osteoarthritis were randomised

Interventions

Experimental intervention

20 mg of hexacetonide triamcinolone plus 6 ml of hylan GF‐20, single intra‐articular injection

Control intervention

6 ml of hylan GF‐20, single intra‐articular injection

Outcomes

Maximum follow‐up: 24 weeks

Outcome data (VAS, WOMAC, and Lequesne) not extractable

Notes

Singh 1996

Methods

Unclear

Participants

Unclear

Interventions

Unclear

Outcomes

Outcome data not extractable

Notes

ICOAP: Intermittent and Constant Osteoarthritis Pain
KOOS: Knee Injury and Osteoarthritis Outcome Score
MRI: magnetic resonance imaging
VAS: visual analogue scale
WOMAC: Western Ontario and McMaster Universities Arthritis Index

Data and analyses

Open in table viewer
Comparison 1. Pain

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain ‐ Main Show forest plot

26

1749

Std. Mean Difference (Random, 95% CI)

‐0.40 [‐0.58, ‐0.22]

Analysis 1.1

Comparison 1 Pain, Outcome 1 Pain ‐ Main.

Comparison 1 Pain, Outcome 1 Pain ‐ Main.

2 Pain ‐ Timepoints Show forest plot

26

Std. Mean Difference (Random, 95% CI)

Subtotals only

Analysis 1.2

Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.

Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.

2.1 Pain‐ 1‐2 week

16

1041

Std. Mean Difference (Random, 95% CI)

‐0.48 [‐0.70, ‐0.27]

2.2 Pain‐ 4‐6 week

22

1529

Std. Mean Difference (Random, 95% CI)

‐0.41 [‐0.61, ‐0.21]

2.3 Pain‐ 3 months

18

1233

Std. Mean Difference (Random, 95% CI)

‐0.22 [‐0.44, 0.00]

2.4 Pain‐ 6 months

7

526

Std. Mean Difference (Random, 95% CI)

‐0.07 [‐0.25, 0.11]

Open in table viewer
Comparison 2. Function

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Function ‐ Main Show forest plot

15

1014

Std. Mean Difference (Random, 95% CI)

‐0.33 [‐0.56, ‐0.09]

Analysis 2.1

Comparison 2 Function, Outcome 1 Function ‐ Main.

Comparison 2 Function, Outcome 1 Function ‐ Main.

2 Function ‐ Timepoints Show forest plot

15

Std. Mean Difference (Random, 95% CI)

Subtotals only

Analysis 2.2

Comparison 2 Function, Outcome 2 Function ‐ Timepoints.

Comparison 2 Function, Outcome 2 Function ‐ Timepoints.

2.1 Function ‐ 1‐2 weeks

10

763

Std. Mean Difference (Random, 95% CI)

‐0.43 [‐0.72, ‐0.14]

2.2 Function ‐ 4‐6 weeks

12

818

Std. Mean Difference (Random, 95% CI)

‐0.36 [‐0.63, ‐0.09]

2.3 Function ‐ 3 months

11

800

Std. Mean Difference (Random, 95% CI)

‐0.13 [‐0.37, 0.10]

2.4 Function ‐ 6 months

4

328

Std. Mean Difference (Random, 95% CI)

0.06 [‐0.16, 0.28]

Open in table viewer
Comparison 3. Quality of life

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Quality of life ‐ Main Show forest plot

2

184

Std. Mean Difference (Random, 95% CI)

‐0.01 [‐0.30, 0.28]

Analysis 3.1

Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.

Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.

Open in table viewer
Comparison 4. Number of participants experiencing any adverse event

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants experiencing any adverse event ‐ Main Show forest plot

2

84

Risk Ratio (IV, Random, 95% CI)

0.89 [0.64, 1.23]

Analysis 4.1

Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.

Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.

Open in table viewer
Comparison 5. Number of participants who withdraw because of adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants who with draw because of adverse events ‐Main Show forest plot

2

204

Risk Ratio (IV, Random, 95% CI)

0.33 [0.05, 2.07]

Analysis 5.1

Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.

Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.

Open in table viewer
Comparison 6. Number of participants experiencing any serious adverse event

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants experiencing any serious adverse event ‐ Main Show forest plot

5

331

Risk Ratio (IV, Random, 95% CI)

0.63 [0.15, 2.67]

Analysis 6.1

Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.

Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.

Open in table viewer
Comparison 7. Joint space narrowing

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Joint space narrowing ‐ Main Show forest plot

1

68

Std. Mean Difference (Random, 95% CI)

‐0.02 [‐0.49, 0.46]

Analysis 7.1

Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.

Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.

Study flow chart. *records with the exact same bibliographic information of another already‐screened record.
Figuras y tablas -
Figure 1

Study flow chart. *records with the exact same bibliographic information of another already‐screened record.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Pain, outcome: 1.1 Pain ‐ Main.
Figuras y tablas -
Figure 3

Forest plot of comparison: 1 Pain, outcome: 1.1 Pain ‐ Main.

Contour‐enhanced funnel plot for effects on knee pain. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs
Figuras y tablas -
Figure 4

Contour‐enhanced funnel plot for effects on knee pain. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs

Forest plot of comparison: 1 Pain, outcome: 1.2 Pain ‐ Time points. P for trend = 0.001
Figuras y tablas -
Figure 5

Forest plot of comparison: 1 Pain, outcome: 1.2 Pain ‐ Time points. P for trend = 0.001

Forest plot of comparison: 2 Function, outcome: 2.1 Function ‐ Main.
Figuras y tablas -
Figure 6

Forest plot of comparison: 2 Function, outcome: 2.1 Function ‐ Main.

Contour‐enhanced funnel plot for effects on knee function. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs
Figuras y tablas -
Figure 7

Contour‐enhanced funnel plot for effects on knee function. Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs

Forest plot of comparison: 2 Function, outcome: 2.2 Function ‐ Time points. P for trend = 0.011
Figuras y tablas -
Figure 8

Forest plot of comparison: 2 Function, outcome: 2.2 Function ‐ Time points. P for trend = 0.011

Forest plot of comparison: 3 Quality of life, outcome: 3.1 Quality of life ‐ Main.
Figuras y tablas -
Figure 9

Forest plot of comparison: 3 Quality of life, outcome: 3.1 Quality of life ‐ Main.

Forest plot of comparison: 7 Joint space narrowing, outcome: 7.1 Joint space narrowing ‐ Main.
Figuras y tablas -
Figure 10

Forest plot of comparison: 7 Joint space narrowing, outcome: 7.1 Joint space narrowing ‐ Main.

Forest plot of comparison: 4 Number of participants experiencing any adverse event, outcome: 4.1 Number of participants experiencing any adverse event ‐ Main.
Figuras y tablas -
Figure 11

Forest plot of comparison: 4 Number of participants experiencing any adverse event, outcome: 4.1 Number of participants experiencing any adverse event ‐ Main.

Forest plot of comparison: 5 Number of participants who withdraw because of adverse events, outcome: 5.1 Number of participants who withdraw because of adverse events ‐Main.
Figuras y tablas -
Figure 12

Forest plot of comparison: 5 Number of participants who withdraw because of adverse events, outcome: 5.1 Number of participants who withdraw because of adverse events ‐Main.

Forest plot of comparison: 6 Number of participants experiencing any serious adverse event, outcome: 6.1 Number of participants experiencing any serious adverse event ‐ Main.
Figuras y tablas -
Figure 13

Forest plot of comparison: 6 Number of participants experiencing any serious adverse event, outcome: 6.1 Number of participants experiencing any serious adverse event ‐ Main.

Comparison 1 Pain, Outcome 1 Pain ‐ Main.
Figuras y tablas -
Analysis 1.1

Comparison 1 Pain, Outcome 1 Pain ‐ Main.

Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.
Figuras y tablas -
Analysis 1.2

Comparison 1 Pain, Outcome 2 Pain ‐ Timepoints.

Comparison 2 Function, Outcome 1 Function ‐ Main.
Figuras y tablas -
Analysis 2.1

Comparison 2 Function, Outcome 1 Function ‐ Main.

Comparison 2 Function, Outcome 2 Function ‐ Timepoints.
Figuras y tablas -
Analysis 2.2

Comparison 2 Function, Outcome 2 Function ‐ Timepoints.

Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.
Figuras y tablas -
Analysis 3.1

Comparison 3 Quality of life, Outcome 1 Quality of life ‐ Main.

Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.
Figuras y tablas -
Analysis 4.1

Comparison 4 Number of participants experiencing any adverse event, Outcome 1 Number of participants experiencing any adverse event ‐ Main.

Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.
Figuras y tablas -
Analysis 5.1

Comparison 5 Number of participants who withdraw because of adverse events, Outcome 1 Number of participants who with draw because of adverse events ‐Main.

Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.
Figuras y tablas -
Analysis 6.1

Comparison 6 Number of participants experiencing any serious adverse event, Outcome 1 Number of participants experiencing any serious adverse event ‐ Main.

Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.
Figuras y tablas -
Analysis 7.1

Comparison 7 Joint space narrowing, Outcome 1 Joint space narrowing ‐ Main.

Intra‐articular corticosteroid compared with sham injection for osteoarthritis of the knee

Patient or population: participants with osteoarthritis of the knee

Settings: various orthopaedic or rheumatology clinics

Intervention: intra‐articular corticosteroid

Comparison: sham injection

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Sham injection

Intra‐articular corticosteroid

Pain intensity

Various pain scales.

(median follow‐up: 12 weeks)

‐1.8 cm change on 10‐cm VAS1
29% improvement

‐2.8 cm change
(Δ ‐1.0 cm, ‐1.5 to ‐0.6)2

46% improvement
(Δ 17%, 10% to 25%)3

SMD ‐0.40 (‐0.58 to ‐0.22)

Predictive interval (‐1.20 to 0.40)

1749

(26)

⊕⊕⊝⊝
low9

NNTB 8 (95% CI 6 to 13)4

Function

Various function scales.

(median follow‐up: 12 weeks)

‐1.2 units on WOMAC (range 0 to 10)1
21% improvement

‐1.9 units on WOMAC
(Δ ‐0.7, ‐1.2 to ‐0.2)5

34% improvement
(Δ 13%, 4% to 22%)6

SMD ‐0.33 (‐0.56 to ‐0.09)

Predictive interval (‐1.19 to 0.54)

1014

(15)

⊕⊕⊝⊝
low9

NNTB 10 (95% CI 7 to 33)7

Number of participants experiencing any adverse event

(median follow‐up: 17 weeks)

150 per 1000 participant‐years8

134 per 1000 participant‐years
(96 to 185)

RR 0.89 (0.64 to 1.23)

84

(2)

⊕⊕⊝⊝
low10

Little evidence of harmful effect (NNTB not statistically significant)

Number of participants who withdraw because of adverse events

(median follow‐up: 25 weeks)

17 per 1000 participant‐years8

6 per 1000 participant‐years
(1 to 35)

RR 0.33 (0.05 to 2.07)

204

(2)

⊕⊕⊝⊝
low10

Little evidence of harmful effect (NNTB not statistically significant)

Number of participants experiencing any serious adverse event

(median follow‐up: 26 weeks)

4 per 1000 participant‐years8

3 per 1000 participant‐years
(1 to 11)

RR 0.63 (0.15 to 2.67)

331

(5)

⊕⊕⊝⊝
low10

Little evidence of harmful effect (NNTB not statistically significant)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NNTB: number needed to treat for an additional beneficial outcome; RR: risk ratio; SMD: standardised mean difference; VAS: visual analogue scale; WOMAC: Western Ontario and McMaster Universities Arthritis Index

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Median reduction as observed across placebo groups in large osteoarthritis trials (see methods section, Nüesch 2009).
2 SMDs were back‐transformed onto a 10‐cm visual analogue scale (VAS) on the basis of a typical pooled standard deviation (SD) of 2.5 cm in large trials that assessed pain using a VAS and expressed as change based on an assumed standardised reduction of 0.72 SD units in the control group.
3 Percentage of improvement was calculated based on median observed pain at baseline across control groups of large osteoarthritis trials of 6.1 cm on 10‐cm VAS (Nüesch 2009).
4 Absolute response risks for pain in the control groups were assumed 31% (see methods section).

5 SMDs were back‐transformed onto a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability score ranging from 0 to 10 on the basis of a typical pooled SD of 2.1 in trials that assessed function using WOMAC disability scores and expressed as change based on an assumed standardised reduction of 0.58 SD units in the control group.
6 Percentage of improvement was calculated based on median observed WOMAC function scores at baseline across control groups of large osteoarthritis trials of 5.6 units (Nüesch 2009).
7 Absolute response risks for function in the control groups were assumed 26% (see methods section).
8 Median control risk across placebo groups in large osteoarthritis trials (see methods section, Nüesch 2009).

9 Downgraded (2 levels) because: Most studies that reported this outcome are of high or unclear risk of bias, and statistical heterogeneity is large.

10 Downgraded (3 levels) because: 50% or more of the studies that reported this outcome are of high or unclear risk of bias, and the confidence interval of the pooled estimate is wide and includes the null effect.

Figuras y tablas -
Table 1. Stratified analyses: Pain

Variable

Number of studies

N of participants corticosteroids

N of participants control

Pain intensity SMD (95% CI)

Heterogeneity I2 (%)

P value*

All trials

26

922

827

‐0.40 (‐0.58 to ‐0.22)

68%

Allocation concealment

0.15

Adequate

2

88

83

‐0.16 (‐0.46 to 0.14)

0%

Inadequate or unclear

24

834

744

‐0.42 (‐0.62 to ‐0.22)

69%

Blinding of participants

0.64

Adequate

6

220

218

‐0.34 (‐0.61 to ‐0.06)

49%

Inadequate or unclear

20

702

609

‐0.42 (‐0.65 to ‐0.19)

72%

Blinding of therapists

0.45

Adequate

3

92

92

‐0.24 (‐0.66 to 0.17)

44%

Inadequate or unclear

23

830

735

‐0.42 (‐0.62 to ‐0.22)

70%

Intention‐to‐treat analysis

0.29

Yes

9

236

233

‐0.26 (‐0.57 to 0.06)

59%

No or unclear

17

686

594

‐0.47 (‐0.69 to ‐0.24)

71%

Type of control intervention

0.08

Sham injection

19

614

526

‐0.50 (‐0.72 to ‐0.28)

65%

No intervention

7

284

280

‐0.18 (‐0.47 to 0.11)

63%

Funding independent of industry

0.80

Yes

11

341

333

‐0.37 (‐0.55 to ‐0.18)

26%

No or unclear

15

581

494

‐0.41 (‐0.70 to ‐0.12)

78%

Trial size

0.05

≥ 50 per trial group

3

205

204

‐0.13 (‐0.37 to 0.12)

34%

< 50 per trial group

23

717

623

‐0.44 (‐0.65 to ‐0.24)

67%

Trial size

0.013

≥ 100 per trial group

1

103

103

0.00 (‐0.27 to 0.27)

N/A

< 100 per trial group

25

819

724

‐0.42 (‐0.61 to ‐0.23)

66%

Publication type

0.93

Full journal article

22

785

706

‐0.40 (‐0.61 to ‐0.20)

70%

Other type or unpublished material

4

137

121

‐0.38 (‐0.84 to ‐0.08)

65%

Ultrasound guidance of injections

0.71

Yes

2

70

70

‐0.62 (‐1.83 to 0.58)

89%

No or unclear

24

852

757

‐0.39 (‐0.57 to ‐0.20)

67%

Use of local anaesthetic

0.41

Yes

5

172

157

‐0.55 (‐0.93 to ‐0.16)

62%

No or unclear

21

750

670

‐0.36 (‐0.57 to ‐0.15)

70%

Concomitant viscosupplementation

0.08

Yes

4

129

127

‐0.16 (‐0.42 to 0.09)

4%

No or unclear

22

793

700

‐0.46 (‐0.67 to ‐0.25)

71%

Concomitant joint lavage

≤ 0.001

Yes

4

197

187

‐0.06 (‐0.26 to 0.15)

0%

No or unclear

26

725

640

‐0.57 (‐0.78 to ‐0.35)

72%

Use of crystalline preparation

0.82

Yes

18

623

562

‐0.47 (‐0.69 to ‐0.24)

72%

No or unclear

12

299

265

‐0.52 (‐0.90 to ‐0.14)

76%

Prednisolone equivalence dose

0.53

≥ 50 mg

17

520

470

‐0.55 (‐0.85 to ‐0.25)

80%

< 50 mg

13

402

357

‐0.43 (‐0.66 to ‐0.20)

56%

Number of randomised comparisons are shown in "number of studies" for stratified analyses according to use of lavage as co‐intervention, crystalline preparation, prednisolone equivalence. *P value for interaction. N/A: not available.

CI: confidence interval
SMD: standardised mean difference

Figuras y tablas -
Table 1. Stratified analyses: Pain
Table 2. Stratified analyses: Function

Variable

Number of studies

N of participants corticosteroids

N of participants control

Function SMD (95% CI)

Heterogeneity I2 (%)

P value*

All trials

15

546

468

‐0.33 (‐0.56 to ‐0.09)

69%

Allocation concealment

0.25

Adequate

2

88

83

‐0.09 (‐0.49 to 0.32)

43%

Inadequate or unclear

13

458

385

‐0.37 (‐0.64 to ‐0.10)

72%

Blinding of participants

0.97

Adequate

5

201

199

‐0.32 (‐0.82 to 0.18)

83%

Inadequate or unclear

10

345

269

‐0.33 (‐0.59 to ‐0.07)

58%

Blinding of therapists

0.78

Adequate

2

75

75

‐0.48 (‐1.65 to 0.70)

91%

Inadequate or unclear

13

471

393

‐0.31 (‐0.55 to ‐0.06)

66%

Intention‐to‐treat analysis

0.49

Yes

5

161

159

‐0.21 (‐0.59 to 0.17)

62%

No or unclear

10

385

309

‐0.38 (‐0.69 to ‐0.07)

73%

Type of control intervention

0.031

Sham injection

11

409

334

‐0.45 (‐0.74 to ‐0.15)

73%

No intervention

4

137

134

‐0.01 (‐0.27 to 0.25)

13%

Funding independent of industry

0.73

Yes

9

310

302

‐0.36 (‐0.66 to ‐0.07)

68%

No or unclear

6

236

166

‐0.27 (‐0.71 to 0.16)

76%

Trial size

0.023

≥ 50 per trial group

2

102

101

0.05 (‐0.23 to 0.32)

0%

< 50 per trial group

13

444

367

‐0.40 (‐0.67 to ‐0.13)

70%

Trial size

N/A

≥ 100 per trial group

0

0

0

N/A

N/A

< 100 per trial group

15

546

468

‐0.33 (‐0.56 to ‐0.09)

69%

Publication type

0.023

Full journal article

14

514

438

‐0.37 (‐0.61 to ‐0.13)

68%

Other type or unpublished material

1

32

30

0.28 (‐0.22 to 0.78)

N/A

Ultrasound guidance of injections

0.49

Yes

2

70

70

‐0.14 (‐0.70 to 0.43)

58%

No or unclear

13

476

398

‐0.36 (‐0.62 to ‐0.09)

71%

Use of local anaesthetic

0.34

Yes

4

105

105

‐0.60 (‐1.25 to 0.05)

78%

No or unclear

11

441

363

‐0.25 (‐0.51 to 0.00)

68%

Concomitant viscosupplementation

0.06

Yes

2

85

84

‐0.00 (‐0.30 to 0.30)

0%

No or unclear

13

461

384

‐0.39 (‐0.66 to ‐0.12)

72%

Concomitant joint lavage

0.18

Yes

3

94

84

‐0.13 (‐0.55 to 0.28)

48%

No or unclear

16

452

384

‐0.46 (‐0.71 to ‐0.21)

70%

Use of crystalline preparation

0.66

Yes

12

365

319

‐0.37 (‐0.66 to ‐0.08)

73%

No or unclear

7

181

149

‐0.47 (‐0.83 to ‐0.11)

61%

Prednisolone equivalence dose

0.16

≥ 50 mg

12

328

277

‐0.52 (‐0.83 to ‐0.20)

74%

< 50 mg

7

218

191

‐0.22 (‐0.48 to 0.05)

47%

Number of randomised comparisons are shown in "number of studies" for stratified analyses according to use of lavage as co‐intervention, crystalline preparation, prednisolone equivalence. *P value for interaction. N/A: not available.

CI: confidence interval
SMD: standardised mean difference

Figuras y tablas -
Table 2. Stratified analyses: Function
Comparison 1. Pain

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain ‐ Main Show forest plot

26

1749

Std. Mean Difference (Random, 95% CI)

‐0.40 [‐0.58, ‐0.22]

2 Pain ‐ Timepoints Show forest plot

26

Std. Mean Difference (Random, 95% CI)

Subtotals only

2.1 Pain‐ 1‐2 week

16

1041

Std. Mean Difference (Random, 95% CI)

‐0.48 [‐0.70, ‐0.27]

2.2 Pain‐ 4‐6 week

22

1529

Std. Mean Difference (Random, 95% CI)

‐0.41 [‐0.61, ‐0.21]

2.3 Pain‐ 3 months

18

1233

Std. Mean Difference (Random, 95% CI)

‐0.22 [‐0.44, 0.00]

2.4 Pain‐ 6 months

7

526

Std. Mean Difference (Random, 95% CI)

‐0.07 [‐0.25, 0.11]

Figuras y tablas -
Comparison 1. Pain
Comparison 2. Function

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Function ‐ Main Show forest plot

15

1014

Std. Mean Difference (Random, 95% CI)

‐0.33 [‐0.56, ‐0.09]

2 Function ‐ Timepoints Show forest plot

15

Std. Mean Difference (Random, 95% CI)

Subtotals only

2.1 Function ‐ 1‐2 weeks

10

763

Std. Mean Difference (Random, 95% CI)

‐0.43 [‐0.72, ‐0.14]

2.2 Function ‐ 4‐6 weeks

12

818

Std. Mean Difference (Random, 95% CI)

‐0.36 [‐0.63, ‐0.09]

2.3 Function ‐ 3 months

11

800

Std. Mean Difference (Random, 95% CI)

‐0.13 [‐0.37, 0.10]

2.4 Function ‐ 6 months

4

328

Std. Mean Difference (Random, 95% CI)

0.06 [‐0.16, 0.28]

Figuras y tablas -
Comparison 2. Function
Comparison 3. Quality of life

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Quality of life ‐ Main Show forest plot

2

184

Std. Mean Difference (Random, 95% CI)

‐0.01 [‐0.30, 0.28]

Figuras y tablas -
Comparison 3. Quality of life
Comparison 4. Number of participants experiencing any adverse event

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants experiencing any adverse event ‐ Main Show forest plot

2

84

Risk Ratio (IV, Random, 95% CI)

0.89 [0.64, 1.23]

Figuras y tablas -
Comparison 4. Number of participants experiencing any adverse event
Comparison 5. Number of participants who withdraw because of adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants who with draw because of adverse events ‐Main Show forest plot

2

204

Risk Ratio (IV, Random, 95% CI)

0.33 [0.05, 2.07]

Figuras y tablas -
Comparison 5. Number of participants who withdraw because of adverse events
Comparison 6. Number of participants experiencing any serious adverse event

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants experiencing any serious adverse event ‐ Main Show forest plot

5

331

Risk Ratio (IV, Random, 95% CI)

0.63 [0.15, 2.67]

Figuras y tablas -
Comparison 6. Number of participants experiencing any serious adverse event
Comparison 7. Joint space narrowing

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Joint space narrowing ‐ Main Show forest plot

1

68

Std. Mean Difference (Random, 95% CI)

‐0.02 [‐0.49, 0.46]

Figuras y tablas -
Comparison 7. Joint space narrowing