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Tacrólimus tópico para la dermatitis atópica

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References

Referencias de los estudios incluidos en esta revisión

Antiga 2010 {published data only}

Antiga E, Volpi W, Torchia D, Fabbri P, Caproni M. Effects of tacrolimus ointment on Toll‐like receptors in atopic dermatitis. Clinical & Experimental Dermatology 2011;36(3):235‐41. [MEDLINE: 21070333]CENTRAL

Bieber 2007 {published data only}

Bieber T, Vick K, Folster‐Holst R, Belloni‐Fortina A, Stadtler G, Worm M, et al. Efficacy and safety of methylprednisolone aceponate ointment 0.1% compared to tacrolimus 0.03% in children and adolescents with an acute flare of severe atopic dermatitis. Allergy 2007;62(2):184‐9. [MEDLINE: 17298428]CENTRAL

Boguniewicz 1998 {published data only}

Boguniewicz M, Fiedler VC, Raimer S, Lawrence ID, Leung DY, Hanifin JM. A randomized, vehicle‐controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. Journal of Allergy & Clinical Immunology 1998;102(4 Pt 1):637‐44. [MEDLINE: 9802373]CENTRAL

Caproni 2007 {published data only}

Caproni M, Torchia D, Antiga E, Terranova M, Volpi W, del Bianco E, et al. The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study. British Journal of Dermatology 2007;156(2):312‐9. [MEDLINE: 17223872]CENTRAL

Doss 2010 {published data only}

Doss N, Kamoun MR, Dubertret L, Cambazard F, Remitz A, Lahfa M, et al. Efficacy of tacrolimus 0.03% ointment as second‐line treatment for children with moderate‐to‐severe atopic dermatitis: evidence from a randomized, double‐blind non‐inferiority trial vs. fluticasone 0.005% ointment. Pediatric Allergy & Immunology 2010;21(2 Pt 1):321‐9. [MEDLINE: 19563466]CENTRAL

Dou 2006 {published data only}

Dou X, Liu L‐L, Xie Z‐Q, Chen L‐J, Li L, Feng S‐Y, et al. The impact of tacrolimus ointment on health‐related quality of life of Chinese adult and pediatric patients with atopic dermatitis (Chinese). Journal of Clinical Dermatology 2006;35(1):50‐2. CENTRAL

Draelos 2005 {published data only}

Draelos Z, Nayak A, Pariser D, Shupack JL, Chon K, Abrams B, et al. Pharmacokinetics of topical calcineurin inhibitors in adult atopic dermatitis: a randomized, investigator‐blind comparison. Journal of the American Academy of Dermatology 2005;53(4):602‐9. [MEDLINE: 16198779]CENTRAL

Fleischer 2007 {published data only}

Fleischer AB, Abramovits W, Breneman D, Jaracz E, US/Canada tacrolimus ointment study group. Tacrolimus ointment is more effective than pimecrolimus cream in adult patients with moderate to very severe atopic dermatitis. Journal of Dermatological Treatment 2007;18(3):151‐7. [MEDLINE: 17538803]CENTRAL

Hanifin 2001 {published data only}

Hanifin JM, Ling MR, Langley R, Breneman D, Rafal E. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. Journal of the American Academy of Dermatology 2001;44(Suppl 1):S28‐38. [EMBASE: 2001020450]CENTRAL
Soter NA, Fleischer Jr AB, Webster GF, Monroe E, Lawrence I. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. Journal of the American Academy of Dermatology 2001;44(1 Suppl):S39‐46. [DOI: 10.1067/mjd.2001.109817; EMBASE: 2001020451]CENTRAL

Hung 2007 {published data only}

Hung SH, Lin YT, Chu CY, Lee CC, Liang TC, Yang YH, et al. Staphylococcus colonization in atopic dermatitis treated with fluticasone or tacrolimus with or without antibiotics. Annals of Allergy, Asthma, & Immunology 007;98(1):51‐6. [MEDLINE: 17225720]CENTRAL

Kempers 2004 {published data only}

Kempers S, Boguniewicz M, Carter E, Jarratt M, Pariser D, Stewart D, et al. A randomized investigator‐blinded study comparing pimecrolimus cream 1% with tacrolimus ointment 0.03% in the treatment of pediatric patients with moderate atopic dermatitis. Journal of the American Academy of Dermatology 2004;51(4):515‐25. [MEDLINE: 15389185]CENTRAL

Otsuki 2003 {published data only}

Otsuki, M, Kawashima, M, Shibata, Y, Nakagawa, H, Harada, S. Efficacy and Safety of FK506 (Tacrolimus) Ointment in Children with Atopic Dermatitis‐Phase III Double‐blinded Comparison with Vehicle Ointment. Journal of Clinical Therapeutics & Medicines (Rinsho Iyaku) 2003;19:569‐95. CENTRAL

Pacor 2004 {published data only}

Pacor ML, Di Lorenzo G, Martinelli N, Mansueto P, Rini GB, Corrocher R. Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study. Clinical & Experimental Allergy 2004;34(4):639‐45. [MEDLINE: 15080819]CENTRAL

Paller 2001 {published data only}

Paller A, Eichenfield LF, Leung DY, Stewart D, Appell M. A 12‐week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. Journal of the American Academy of Dermatology 2001;44(1 Suppl):S47‐57. [MEDLINE: 11145795]CENTRAL

Paller 2005 {published data only}

Abramovits W, Fleischer AB, Jaracz E, Breneman D. Adult patients with moderate atopic dermatitis: tacrolimus ointment versus pimecrolimus cream. Journal of Drugs in Dermatology 2008;7(12):1153‐8. [MEDLINE: 19137769]CENTRAL
Paller AS, Lebwohl M, Fleischer AB, Antaya R, Langley RG, Kirsner RS, et al. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies. Journal of the American Academy of Dermatology 2005;52(5):810‐22. [MEDLINE: 15858471]CENTRAL

Reitamo 2002a {published data only}

Reitamo S, Rustin M, Ruzicka T, Cambazard F, Kalimo K, Friedmann PS, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. Journal of Allergy & Clinical Immunology 2002;109(3):547‐55. [MEDLINE: 11898005]CENTRAL

Reitamo 2002b {published data only}

Reitamo S, Van Leent EJ, Ho V, Harper J, Ruzicka T, Kalimo K, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis. Journal of Allergy & Clinical Immunology 2002;109(3):539‐46. [MEDLINE: 11898004]CENTRAL

Reitamo 2004 {published data only}

Reitamo S, Harper J, Bos JD, Cambazard F, Bruijnzeel‐Koomen C, Valk P, et al. 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double‐blind controlled trial. British Journal of Dermatology 2004;150(3):554‐62. [MEDLINE: 15030341]CENTRAL

Reitamo 2005 {published data only}

Mandelin J, Remitz A, Virtanen H, Reitamo S. One‐year treatment with 0.1% tacrolimus ointment versus a corticosteroid regimen in adults with moderate to severe atopic dermatitis: A randomized, double‐blind, comparative trial. Acta Dermato‐Venereologica 2010;90(2):170‐4. [DOI: 10.2340/00015555‐0803; MEDLINE: 20169301]CENTRAL
Poole CD, Chambers C, Allsopp R, Currie CJ. Quality of life and health‐related utility analysis of adults with moderate and severe atopic dermatitis treated with tacrolimus ointment vs. topical corticosteroids. Journal of the European Academy of Dermatology & Venereology 2010;24(6):674‐8. [DOI: 10.1111/j.1468‐3083.2009.03485.x; MEDLINE: 20565562]CENTRAL
Reitamo S, Ortonne JP, Sand C, Cambazard F, Bieber T, Folster‐Holst R, et al. A multicentre, randomized, double‐blind, controlled study of long‐term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis. British Journal of Dermatology 2005;152(6):1282‐9. [MEDLINE: 15948994]CENTRAL

Sikder 2005 {published data only}

Sikder Md AU, Al Mamun S, Khan RM, Chowdhury AH, Khan HM, Hoque MM. Topical 0.03% tacrolimus ointment, 0.05% clobetasone butyrate cream alone and their combination in older children with atopic dermatitis ‐ An open randomized comparative study. Journal of Pakistan Association of Dermatologists 2005;15(4):304‐12. [EMBASE: 2006159825]CENTRAL

Referencias de los estudios excluidos de esta revisión

Arkwright 2006 {published data only}

Arkwright PD, Gillespie MC, Ewing CI, David TJ. Blinded side‐to‐side comparison of topical corticosteroid and tacrolimus ointment in children with moderate to severe atopic dermatitis. Clinical & Experimental Dermatology 2007;32(2):145‐7. [MEDLINE: 17342794]CENTRAL

Chapman 2005 {published data only}

Chapman MS, Schachner LA, Breneman D, Boguniewicz M, Gold MH, Shull T, et al. Tacrolimus ointment 0.03% shows efficacy and safety in pediatric and adult patients with mild to moderate atopic dermatitis. Journal of the American Academy of Dermatology 2005;53(2 Suppl 2):177‐85. [MEDLINE: 16021173]CENTRAL

Dähnhardt‐Pfeiffer 2013 {published data only}

Dähnhardt‐Pfeiffer S, Dähnhardt D, Buchner M, Walter K, Proksch E, Fölster‐Holst R. Comparison of effects of tacrolimus ointment and mometasone furoate cream on the epidermal barrier of patients with atopic dermatitis. Journal Der Deutschen Dermatologischen Gesellschaft 2013;11(5):437‐43. [MEDLINE: 23551950]CENTRAL

del Rosso 2007 {published data only}

Del Rosso JQ, Conte ET. An Investigator‐Blinded Evaluation of Fluocinonide 0.1% Cream in the Treatment of Atopic Dermatitis and Psoriasis Vulgaris. Cosmetic Dermatology 2007;20(9):545‐52. [EMBASE: 2007500429]CENTRAL

Doss 2009 {published data only}

Doss N, Reitamo S, Dubertret L, Fekete GL, Kamoun MR, Lahfa M, et al. Superiority of tacrolimus 0.1% ointment compared with fluticasone 0.005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double‐blind trial. British Journal of Dermatology 2009;161(2):427‐34. [MEDLINE: 19416227]CENTRAL

Gradman 2007 {published data only}

Gradman J, Wolthers OD. Short‐term growth in children with eczema during treatment with topical mometasone furoate and tacrolimus. Acta Paediatrica 2007;96(8):1233‐7. [MEDLINE: 17590198]CENTRAL

Granlund 2001 {published data only}

Granlund H, Remitz A, Kyllonen H, Lauerma AI, Reitamo S. Treatment of Lichenified Atopic Eczema with Tacrolimus Ointment. Acta Dermato‐Venereologica 2001;81(4):314‐5. [MEDLINE: 11720192]CENTRAL

Hebert 2006 {published data only}

Hebert AA, Koo J, Fowler J, Berman B, Rosenberg C, Levitt J. Desoximetasone 0.25% and tacrolimus 0.1% ointments versus tacrolimus alone in the treatment of atopic dermatitis. Cutis 2006;78(5):357‐63. [MEDLINE: 17186796]CENTRAL

Hjelmgren 2007 {published data only}

Hjelmgren J, Svensson A, Jorgensen ET, Lindemalm‐Lundstam B, Ragnarson Tennvall G. Cost‐effectiveness of tacrolimus ointment vs. standard treatment in patients with moderate and severe atopic dermatitis: a health‐economic model simulation based on a patient survey and clinical trial data. British Journal of Dermatology 2007;156(5):913‐21. [MEDLINE: 17263826]CENTRAL

Ishibashi 1997 {published data only}

Ishibashi Y, Nakagawa H, Eto T, Kawashima M, Higaki Y, Harada S, et al. Early Phase II Study of FK506 Ointment on Atopic Dermatitis. Rinsho Iyaku (Journal of Clinical Therapeutics and Medicines) 1997;13(2):317‐39. CENTRAL

Kang 2003 {published data only}

Kang S, Paller A, Soter N, Satoi Y, Rico MJ, Hanifin JM. Safe treatment of head/neck AD with tacrolimus ointment. Journal of Dermatological Treatment 2003;14(2):86‐94. [MEDLINE: 12775315]CENTRAL

Kirsner 2010 {published data only}

Kirsner RS, Heffernan MP, Antaya R. Safety and efficacy of tacrolimus ointment versus pimecrolimus cream in the treatment of patients with atopic dermatitis previously treated with corticosteroids. Acta Dermato‐Venereologica 2010;90(1):58‐64. [MEDLINE: 20107727]CENTRAL

Liu 2005 {published data only}

Liu LL, Dou X, Xie ZQ, Wand D, Zheng ZZ, Wei MH, et al. Efficacy and Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis in Chinese Children. Chinese Journal of Dermatology 2005;38(10):608‐11. CENTRAL

Neumann 2008 {published data only}

Neumann E, Amtage D, Bruckner‐Tuderman L, Mockenhaupt M. A single‐center open‐label long‐term comparison of tacrolimus ointment and topical corticosteroids for treatment of atopic dermatitis. Journal Der Deutschen Dermatologischen Gesellschaft 2008;6(7):548‐53. [MEDLINE: 18248495]CENTRAL

Onumah 2013 {published data only}

Onumah N, Kircik L. Pimecrolimus cream and tacrolimus ointment in the treatment of atopic dermatitis: A pilot study on patient preference. Journal of Drugs in Dermatology 2013;12(10):1145‐8. [MEDLINE: 24085050]CENTRAL

Rahman 2008 {published data only}

Rahman MF, Rashid MM, Sikder AU, Akhtar N, Banu LA, Wahab MA. Efficacy of topical tacrolimus in atopic dermatitis. Journal of Pakistan Association of Dermatologists 2008;18(2):84‐92. [EMBASE: 2008404671]CENTRAL

Reitamo 2009 {published data only}

Reitamo S, Mandelin J, Rubins A, Remitz A, Makela M, Cirule K, et al. The pharmacokinetics of tacrolimus after first and repeated dosing with 0.03% ointment in infants with atopic dermatitis. International Journal of Dermatology 2009;48(4):348‐55. [MEDLINE: 19335418]CENTRAL

Ruzicka 1997 {published data only}

Ruzicka T, Bieber T, Schopf E, Rubins A, Dobozy A, Bos JD, et al. A short‐term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. New England Journal of Medicine 1997;337(12):816‐21. [MEDLINE: 9295241]CENTRAL

Schachner 2005 {published data only}

Schachner LA, Lamerson C, Sheehan MP, Boguniewicz M, Mosser J, Raimer S, et al. Tacrolimus ointment 0.03% is safe and effective for the treatment of mild to moderate atopic dermatitis in pediatric patients: results from a randomized, double‐blind, vehicle‐controlled study. Pediatrics 2005;116(3):e334‐42. [MEDLINE: 16140675]CENTRAL

Takeuchi 2012 {published data only}

Takeuchi S, Saeki H, Tokunaga S, Sugaya M, Ohmatsu H, Tsunemi Y, et al. A randomized, open‐label, multicenter trial of topical tacrolimus for the treatment of pruritis in patients with atopic dermatitis. Annals of Dermatology 2012;24(2):144‐50. [MEDLINE: 22577263]CENTRAL

Torok 2003 {published data only}

Torok HM, Maas‐Irslinger R, Slayton RM. Clocortolone pivalate cream 0.1% used concomitantly with tacrolimus ointment 0.1% in atopic dermatitis. Cutis 2003;72(2):161‐6. [MEDLINE: 12953943]CENTRAL

Won 2004 {published data only}

Won CH, Seo PG, Park YM, Yang JM, Lee KH, Sung KJ, et al. A multicenter trial of the efficacy and safety of 0.03% tacrolimus ointment for atopic dermatitis in Korea. Journal of Dermatological Treatment 2004;15(1):30‐4. [MEDLINE: 14754647]CENTRAL

Xhauflaire‐Uhoda 2007 {published data only}

Xhauflaire‐Uhoda E, Thirion L, Piérard‐Franchimont C, Piérard GE. Comparative effect of tacrolimus and betamethasone valerate on the passive sustainable hydration of the stratum corneum in atopic dermatitis. Dermatology 2007;214(4):328‐32. [MEDLINE: 17460405]CENTRAL

Referencias de los estudios en espera de evaluación

Drake 2001 {published data only}

Drake L, Prendergast M, Maher R, Breneman D, Korman N, Satoi Y, et al. The impact of tacrolimus ointment on health‐related quality of life of adult and pediatric patients with atopic dermatitis. Journal of the American Academy of Dermatology 2001;44(1 Suppl):S65‐72. [MEDLINE: 11145797]CENTRAL

NCT00475605 {published data only}

NCT00475605. APPLES: A Prospective Pediatric Longitudinal Evaluation to Assess the Long‐Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis. clinicaltrials.gov/ct2/show/NCT00475605 (accessed 8 October 2014). CENTRAL

Akdis 2006

Akdis CA, Akdis M, Bieber T, Bindslev‐Jensen C, Boguniewicz M, Eigenmann P, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. Allergy 2006;61(8):969‐987. [MEDLINE: 16867052]

Aldea 2012

Aldea A, Garcia Sanchez‐Colomer M, Fernandez Quintana E, Garcia Saiz M. Paediatric adverse drug reactions reported to the Spanish Pharmacovigilance System from 2004 to 2009. European Journal of Clinical Pharmacology 2012;68(9):1329‐38. [MEDLINE: 22415248]

Allen 2001

Allen A, Siegfried E, Silverman R, Williams ML, Elias PM, Szabo SK, et al. Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Archives of Dermatology 2001;137(6):747‐50. [MEDLINE: 11405764]

Allen 2002

Allen DM, Esterly NB. Significant systemic absorption of tacrolimus after topical application in a patient with lamellar ichthyosis. Archives of Dermatology 2002;138(9):1259‐60. [MEDLINE: 12225004]

Antille 2004

Antille C, Saurat JH, Lubbe J. Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment. Archives of Dermatology 2004;140(4):457‐60. [MEDLINE: 15096374]

Arellano 2007

Arellano FM, Wentworth CE, Arana A, Fernandez C, Paul CF. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. Journal of Investigative Dermatology 2007;127(4):808‐16. [MEDLINE: 17096020]

Arellano 2009

Arellano FM, Arana A, Wentworth CE, Fernandez‐Vidaurre C, Schlienger RG, Conde E. Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom. Journal of Allergy & Clinical Immunology 2009;123(5):1111‐6. [MEDLINE: 19361841]

Ashcroft 2005

Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta‐analysis of randomised controlled trials. BMJ 2005;330(7490):516. [MEDLINE: 15731121]

Ashcroft 2005b

Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta‐analysis of randomised controlled trials. BMJ 2005;330(7490):516. [MEDLINE: 15731121]

Ashcroft 2007

Ashcroft DM, Chen L, Garside R, Stein K, Williams HC. Topical pimecrolimus for eczema. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD005500.pub2]

Asher 2010

Asher MI, Stewart AW, Mallol J, Montefort S, Lai CK, Aït‐Khaled N, et al. Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One. Respiratory Research 2010;11:8. [MEDLINE: 20092649]

Bath‐Hextall 2008

Bath‐Hextall FJ, Delamere FM, Williams HC. Dietary exclusions for established atopic eczema. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD005203.pub2]

Bekersky 2001

Bekersky I, Fitzsimmons W, Tanase A, Maher RM, Hodosh E, Lawrence I. Nonclinical and early clinical development of tacrolimus ointment for the treatment of atopic dermatitis. Journal of the American Academy of Dermatology 2001;44(1 Suppl):S17‐27. [MEDLINE: 11145792]

Bens 2003

Bens G, Boralevi F, Buzenet C, Taïeb A. Topical treatment of Netherton's syndrome with tacrolimus ointment without significant systemic absorption. British Journal of Dermatology 2003;149(1):224‐226. [MEDLINE: 12890237]

Berger 2006

Berger TG, Duvic M, Van Voorhees AS, VanBeek MJ, Frieden IJ, American Academy of Dermatology Association Task Force. The use of topical calcineurin inhibitors in dermatology: safety concerns. Report of the American Academy of Dermatology Association Task Force. Journal of the American Academy of Dermatology 2006;54(5):818‐23. [MEDLINE: 16635663]

Beyeler 2006

Beyeler M, Schmid‐Grendelmeier P, Hafner J. Significantly elevated systemic levels after occlusive application of topical tacrolimus in atopic dermatitis. Dermatology 2006;212(3):260‐261. [MEDLINE: 16549924]

Boguniewicz 2006

Boguniewicz M, Leung DY. Atopic Dermatitis. Journal of Allergy & Clinical Immunology 2006;117(2 Suppl Mini‐Primer):S475‐S480. [MEDLINE: 16455350]

Bos 2010

Bos JD, Brenninkmeijer EE, Schram ME, Middelkamp‐Hup MA, Spuls PI, Smitt JH. Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010;19(4):325‐31. [MEDLINE: 20100192]

Brenninkmeijer 2009

Brenninkmeijer EE, Legierse CM, Sillevis Smitt JH, Last BF, Grootenhuis MA, Bos JD. The course of life of patients with childhood atopic dermatitis. Pediatric Dermatology 2009 Jan‐Feb;26(1):14‐22. [MEDLINE: 19250399]

Breuer 2005

Breuer K, Werfel T, Kapp A. Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. American Journal of Clinical Dermatology 2005;6(2):65‐77. [MEDLINE: 15799678]

Böhme 2001

Böhme M, Svensson A, Kull I, Nordvall SL, Wahlgren CF. Clinical features of atopic dermatitis at two years of age: a prospective, population‐based case‐control study. Acta Dermato‐Venereologica 2001;81(3):193‐7. [MEDLINE: 11558876]

Callen 2007

Callen J, Chamlin S, Eichenfield LF, Ellis C, Girardi M, Goldfarb M, et al. A systematic review of the safety of topical therapies for atopic dermatitis. British Journal of Dermatology 2007;156(2):203‐21. [MEDLINE: 17223859]

Calza 2005

Calza AM, Lubbe J. Tacrolimus ointment‐associated alcohol intolerance in infants receiving ethanol‐containing medication. British Journal of Dermatology 2005;152(3):569. [MEDLINE: 15787832]

Castelo‐Soccio 2012

Castelo‐Soccio L, Di Marcantonio D, Shah P, Lee LW, Treat JR, Yan AC. Induced lentiginosis with use of topical calcineurin inhibitors. Archives of Dermatology 2012;148(6):766‐8. [MEDLINE: 22710469]

Chamlin 2004

Chamlin SL, Frieden IJ, Williams ML, Chren MM. Effects of atopic dermatitis on young American children and their families. Pediatrics 2004;114(3):607‐11. [MEDLINE: 15342828]

Charman 2000

Charman C, Williams H. Outcome Measures of Disease Severity in Atopic Eczema. Archives of Dermatology 2000;136(6):763‐9. [DOI: 10.1001/archderm.136.6.763; MEDLINE: 10871941]

Chen 2010

Chen SL, Yan J, Wang FS. Two topical calcineurin inhibitors for the treatment of atopic dermatitis in pediatric patients: a meta‐analysis of randomized clinical trials. Journal of Dermatological Treatment 2010;21(3):144‐56. [MEDLINE: 20394490]

Cho 2004

Cho M, Puma I, Nguyen D, Schut R, Glesne L. Development of Kaposi's sarcoma in an AIDS patient after treatment with topical tacrolimus. Journal of the American Academy of Dermatology 2004;50(1):149‐50. [MEDLINE: 14699390]

Czarnecka‐Operacz 2012

Czarnecka‐Operacz M, Jenerowicz D. Topical calcineurin inhibitors in the treatment of atopic dermatitis ‐ an update on safety issues. Journal Der Deutschen Dermatologischen Gesellschaft 2012;10(3):167‐72. [MEDLINE: 21974750]

Ehst 2004

Ehst BD, Warshaw EM. Alcohol‐induced application site erythema after topical immunomodulator use and its inhibition by aspirin. Archives of Dermatology 2004;140(8):1014‐5. [MEDLINE: 15313828]

Eichenfield 2014

Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. Journal of the American Academy of Dermatology 2014;70(2):338‐51. [MEDLINE: 24290431]

El‐Batawy 2009

El‐Batawy MM, Bosseila MA, Mashaly HM, Hafez VS. Topical calcineurin inhibitors in atopic dermatitis: a systematic review and meta‐analysis. Journal of Dermatological Science 2009;54(2):76‐87. [MEDLINE: 19303745]

Elbourne 2002

Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. [MEDLINE: 11914310]

Ellis 2012

Ellis CN, Mancini AJ, Paller AS, Simpson EL, Eichenfield LF. Understanding and managing atopic dermatitis in adult patients. Seminars in Cutaneous Medicine & Surgery 2012;31(3 Suppl):S18‐22. [MEDLINE: 23021781]

Ellwood 2001

Ellwood P, Asher MI, Björkstén B, Burr M, Pearce N, Robertson CF. Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and Allergies in Childhood (ISAAC) data. ISAAC Phase One Study Group. European Respiratory Journal 2001 Mar;17(3):436‐43. [MEDLINE: 11405522]

Finch 2010

Finch J, Munhutu MN, Whitaker‐Worth DL. Atopic dermatitis and nutrition. Clinics in Dermatology 2010;28(6):605‐14. [MEDLINE: 21034985]

Fitzpatrick 2008

Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatrick's Dermatology in General Medicine. 7th Edition. Vol. 1, United States: The McGraw‐Hill Companies, 2008.

FK506 Ointment Study Group 2001

FK506 Ointment Study Group. Long‐term study of FK506 (tacrolimus) ointment in patients with atopic dermatitis ‐ analysis at time of completion of 2‐year observation. Journal of Clinical Therapeutics and Medicines 2001;17(5):705‐726.

Fonacier 2005

Fonacier L, Spergel J, Charlesworth EN, Weldon D, Beltrani V, Bernhisel‐Broadbent J, et al. Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology. Journal of Allergy & Clinical Immunology 2005;115(6):1249‐53. [MEDLINE: 15940142]

Fujiwara 2010

Fujiwara S, Okubo Y, Irisawa R, Tsuboi R. Rosaceiform dermatitis associated with topical tacrolimus treatment. Journal of the American Academy of Dermatology 2010;62(6):1050‐2. [MEDLINE: 20466178]

Goldman 2001

Goldman D. Tacrolimus ointment for thetreatment of steroid‐induced rosacea: a preliminary report. Journal of the American Academy of Dermatology 2001;44(6):995‐8. [MEDLINE: 11369912]

Gontijo 2008

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Referencias de otras versiones publicadas de esta revisión

Cury Martins 2012

Cury Martins J, Martins C, Aoki V, Leonardi‐Bee J, Gois AFT, Ishii HA, et al. Topical tacrolimus for atopic dermatitis. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD009864]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Antiga 2010

Methods

RCT

Participants

Adults with moderate to severe AD

Interventions

Tacrolimus ointment 0.1% (12 participants) compared with 17‐butyrate‐hydrocortisone ointment 0.1% (12 participants) (BID) for 3 weeks

Outcomes

  • SCORAD

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants were given a run‐in number on enrolment; the randomisation list was created using Random Allocation Software

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blinded, but there was no interference with the results, as the participant's assessment was not evaluated. In the same way, physicians who gave the drug were not blinded, but they were not the people evaluating the outcomes, thus, also not interfering with the results. (We received this information after contacting the study author)

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The physician that evaluated SCORAD was blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There were 3 losses out of 24 (12.5%) participants; there was no ITT analysis

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Bieber 2007

Methods

RCT (randomised, double‐blind, multicentre, comparative study)

Participants

Paediatric patients (2 to 15 years) with history of moderate to severe AD and a severe flare (IGA > = 4)

Interventions

Tacrolimus ointment 0.03% BID (136 participants) compared with methylprednisolone aceponate 0.1% in the evening and no active treatment ointment in the morning (129 participants) for 3 weeks

Outcomes

  • IGA

  • BSA

  • EASI

  • mEASI

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was done in blocks to achieve balanced randomisation overall and within each centre

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The trial used identical tubes (morning and evening)

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The trial was investigator blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 8 losses out of 265 (3%) participants. ITT analysis was done, and the 'last observation carried forward' principle was applied to impute missing values

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Boguniewicz 1998

Methods

RCT (double‐blind, randomised, multicentre trial)

Participants

Paediatric patients with moderate to severe AD

Interventions

Tacrolimus ointment 0.03% (43 participants) compared with tacrolimus ointment 0.1% (49 participants) versus tacrolimus ointment 0.3% (44 participants) compared with vehicle (44 participants) (BID) for 3 weeks

Outcomes

  • mEASI

  • Physician's global assessment

  • Patient's global assessment

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random sequence was generated within each centre by using permuted blocks of size 8 by means of a centralised computer‐generated randomisation schedule

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The interventions were identical in their appearance (identical coded tubes)

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The interventions were identical in their appearance (identical coded tubes) (blinded to all investigators, participants, and the sponsor)

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 11 out of 180 (6.1%) losses. ITT analysis was done with no reference to the method for imputing missing data

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Caproni 2007

Methods

RCT

Participants

Adults with moderate to severe AD

Interventions

Tacrolimus ointment 0.1% (10 participants) compared with hydrocortisone butyrate 0.1% ointment (10 participants) (BID) for 3 weeks

Outcomes

  • SCORAD

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Participants were randomly assigned

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding was not described

Incomplete outcome data (attrition bias)
All outcomes

High risk

There were 4 losses out of 20 (20%) participants in both groups. There was no ITT analysis

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Doss 2010

Methods

RCT (double‐blind, randomised, non‐inferiority, multicentre trial)

Participants

Paediatric patients (2 to 15 years) with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989)) and insufficient response to topical corticosteroids

Interventions

Tacrolimus ointment 0.03% (240 participants) compared with fluticasone 0.005% ointment (239 participants) (BID) for 3 weeks

Outcomes

  • mEASI

  • Physician's global assessment

  • Patient's global assessment

  • Adverse events

  • Pruritus

  • Quality of sleep

Notes

Moderate‐potency corticosteroids (fluticasone 0.005% ointment)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

1:1: the Data Operations Department, Astellas Pharma, generated the list. Randomisation occurred in the order that the participants passed selection criteria

Allocation concealment (selection bias)

Low risk

Each participant received a unique treatment number, which was printed on sealed boxes containing the ointment tubes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

All interventions had the same appearance

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The study was investigator blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 41 losses out of 479 (8.6%) participants. ITT analysis was done with the last observation carried forward (LOCF) rule

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Dou 2006

Methods

RCT (randomised, multicentre, double‐blind clinical trial)

Participants

Adults with moderate to severe AD

Interventions

Tacrolimus 0.03% ointment (67 participants) compared with tacrolimus 0.1% ointment (68 participants) compared with vehicle ointment (67 participants) (BID) for 3 weeks

Outcomes

  • DLQI

Notes

Children were also evaluated, but the comparison was tacrolimus 0.03% ointment only with placebo (with no active treatment); therefore, we did not include them in the analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The study was randomised using aleatory distribution

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The study was double‐blind, with no description of the method

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

The study was double‐blind, with no description of the method

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Incomplete outcome data were not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Draelos 2005

Methods

RCT (randomised, investigator‐blind, parallel group, multicentre trial)

Participants

Adults with moderate to severe AD

Interventions

Tacrolimus 0.1% ointment (19 participants) compared with pimecrolimus 1% cream (18 participants) (BID) for 13 days

Outcomes

  • IGADA (investigator's global assessment)

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Drug assignment was computer‐generated. (We obtained this information after contacting the author)

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blinded because the intervention was an ointment and the control was a cream, but there was no interference with the results, as the participant's assessment was not evaluated

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The trial investigators were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

The study lost no participants

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Fleischer 2007

Methods

RCT (prospective, randomised, investigator‐blinded, multicentre, comparative trial)

Participants

Adults (> = 16 years) with moderate to severe AD

Interventions

Tacrolimus 0.1% ointment (141 participants) compared with pimecrolimus 1% cream (140 participants) (BID) for 6 weeks

Outcomes

  • IGADA

  • BSA

  • EASI

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A specialised company conducted centralised randomisation

Allocation concealment (selection bias)

Low risk

Allocation was by phone

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blinded because the intervention was an ointment and the control was a cream, but there was no interference with the results, as the participant's assessment was not evaluated

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The outcome investigator was blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There were 64 losses out of 281 (22.8%) participants. ITT analysis was done with last observation carried forward analysis

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Hanifin 2001

Methods

RCT (2 randomised, double‐blind, multicentre studies)

Participants

Adults (> = 16 years) with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment (211 participants) compared with tacrolimus 0.1% ointment (209 participants) compared with vehicle (ointment base) (212 participants) (BID) for 12 weeks

Outcomes

  • Physician's global assessment

  • BSA

  • EASI

  • Pruritus

Notes

Adverse events were reported in an additional paper (Soter 2001)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The study was randomised 1:1:1 within each centre; the method was not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The trial was double blind (but there was no description of the blinding methods)

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

The trial was double blind (but there was no description of the blinding methods)

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There was 1 loss out of 632 (0.16%) participants

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Hung 2007

Methods

RCT (randomised, parallel, open‐label, single centre study)

Participants

9‐month‐old to 33‐year‐old participants with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment alone compared with tacrolimus 0.03% ointment and fusidic acid 2% cream compared with fluticasone propionate 0.05% cream alone compared with fluticasone propionate 0.05% cream and fusidic acid 2% cream (15 participants randomised in each group) (BID) for 8 weeks

Outcomes

  • BSA

  • SCORAD

Notes

Moderate‐potency glucocorticoid (fluticasone propionate 0.05% cream)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The trial was randomised, but the method was not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blinded because of the different treatment appearance, but there was no interference with the results, as the participant's assessment was not evaluated

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessment was not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were no losses

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Kempers 2004

Methods

RCT (multicentre, randomised, investigator‐blind, parallel group study)

Participants

Paediatric patients (2 to 17 years) with moderate AD (IGA)

Interventions

Tacrolimus 0.03% ointment (70 participants) compared with pimecrolimus 1% cream (71 participants) (BID) for 6 weeks

Outcomes

  • IGA

  • BSA

  • Pruritus

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The trial was randomised using a validated telephone system that automates the random assignment of treatment groups to randomisation numbers. A block size of 4 was used

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blinded because the intervention was an ointment and the control was a cream, but there was no interference with the results, as the participant's assessment was not evaluated

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The trial investigators were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 16 losses out of 141 (11.3%) participants. ITT analysis was done with last observation carried forward analysis

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Otsuki 2003

Methods

RCT (randomised, double‐blind, multicentre study)

Participants

Paediatric patients (2 to 15 years) with moderate to severe AD (Rajka and Langeland (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment (72 participants) compared with tacrolimus 0.1% ointment (70 participants) compared with vehicle ointment (71 participants) (BID) for 3 weeks

Outcomes

  • Investigator's global assessment

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Allocation was done through random assignment with a keycode

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The trial was double blind, but there was no description of the blinding methods

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

The trial was double blind, but there was no description of the blinding methods

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 8 losses out of 221 (3.6%) participants. ITT analysis was done with no reference to the method for imputing missing data

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Pacor 2004

Methods

RCT (single centre, randomised, double‐blind, double‐dummy, placebo‐controlled, parallel group study)

Participants

13‐year‐old to 45‐year‐old patients with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.1% ointment BID and placebo tablets (15 participants) compared with ciclosporin 3 mg/kg daily and placebo ointment (15 participants) for 6 weeks

Outcomes

  • SCORAD

  • Adverse events

  • Itch

  • Interference with sleep

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The trial was randomised, but there was no description of the method

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Both groups received tablets and ointment

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Treatments were administered by a person who was unaware of who was participating in the study

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were no losses

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Paller 2001

Methods

RCT (randomised, double‐blind, multicentre trial)

Participants

Children (2 to 15 years) with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment (117 participants) compared with tacrolimus 0.1% ointment (118 participants) compared with vehicle (ointment base) (116 participants) (BID) for 12 weeks

Outcomes

  • Physician's and patient's global assessment

  • Adverse events

  • BSA

  • EASI

  • Pruritus

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Participants were stratified by age and randomised 1:1:1 within each centre. The method was not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The investigator, participants, guardian, and study co‐ordinator were blinded

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The investigator, participants, guardian, and study co‐ordinator were blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There were 40 losses out of 235 (17.0%) participants. ITT analysis was done, but the method was not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Paller 2005

Methods

RCT (multicentre, randomised, investigator‐blinded study)

Participants

Paediatric patients (2 to 15 years) with moderate to severe AD (IGADA)

Interventions

Tacrolimus 0.1% ointment (112 participants) compared with pimecrolimus 1% cream (113 participants) (BID) for 6 weeks

Outcomes

  • IGADA

  • BSA

  • EASI

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Allocation was 1:1; numbers were assigned sequentially and stratified by age. A controlled randomisation system at the EMMES Corporation (Rockville, Md) conducted randomisation and stratification

Allocation concealment (selection bias)

Low risk

A study co‐ordinator, independently of the examining physician, placed a call to a centralised randomisation centre to obtain the next sequential participant number and drug assignment

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blinded because the intervention was an ointment and the control was a cream, but there was no interference with the results, as the participant's assessment was not evaluated

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The study was investigator blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There were 274 losses out of 1065 (25.7%) participants. ITT analysis was done, but the method was not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Reitamo 2002a

Methods

RCT (multicentre, randomised, double‐blind, parallel group study)

Participants

Adults (16 to 70 years) with moderate to severe AD

Interventions

Tacrolimus 0.03% ointment (193 participants) compared with tacrolimus 0.1% ointment (191 participants) compared with hydrocortisone butyrate 0.1% ointment (186 participants) (BID) for 3 weeks

Outcomes

  • BSA per cent

  • mEASI

  • Physician's global assessment

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation occurred in the order that the participants passed the selection criteria (parallel groups: 1:1:1). The sponsor supplied each centre a unique block of sequentially ordered participant numbers from a randomisation list

Allocation concealment (selection bias)

Low risk

For treatment allocation, an ointment supply box bearing a unique participant number was dispensed

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Identical tubes were used with no information

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Identical tubes were used with no information

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 61 losses out of 570 (10.7%) participants. ITT analysis was done, but the method was not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Reitamo 2002b

Methods

RCT (multicentre, randomised, double‐blind, parallel group study)

Participants

Paediatric patients (2 to 15 years) with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment (189 participants) compared with tacrolimus 0.1% ointment (186 participants) compared with hydrocortisone acetate 1% ointment (185 participants) (BID) for 3 weeks

Outcomes

  • mEASI

  • Physician's global assessment

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation occurred in the order that the participants passed the selection criteria (parallel groups: 1:1:1), stratified by centre and age. The sponsor supplied each centre with a unique block of sequentially ordered participant numbers from a randomisation list

Allocation concealment (selection bias)

Low risk

For treatment allocation, an ointment supply box bearing a unique participant number was dispensed

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Identical tubes were used with no information

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The trial was investigator blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 54 losses out of 560 (9.6%) participants. ITT analysis was done, but the method was not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Reitamo 2004

Methods

RCT (randomised, double‐blind, multicentre, comparative study)

Participants

Paediatric patients (2 to 15 years) with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus ointment 0.03% once daily (207 participants) compared with tacrolimus ointment 0.03% BID (210 participants) compared with hydrocortisone acetate ointment 1% BID (207 participants) for 3 weeks

Outcomes

  • Physician's global assessment

  • Patient's global assessment

  • EASI

  • mEASI

  • Itch

  • Quality of sleep

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The trial had 1:1:1 stratification by centre and age. The sponsor supplied each centre with a unique block of sequentially ordered participant numbers from a randomisation list. Randomisation occurred in the order that the participants passed the selection criteria

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

2 sets of identical tubes (morning and evening) were used for all of the groups

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The trial was investigator blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were 88 losses out of 624 (14.1%) participants. ITT analysis was done, but the method was not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Reitamo 2005

Methods

RCT (double‐blind, randomised, comparative, phase III study)

Participants

Adults with moderate to severe AD

Interventions

Tacrolimus ointment 0.1% (487 participants) compared with hydrocortisone butyrate ointment 0.1% on the trunk and extremities and hydrocortisone acetate ointment 1% on the face and neck (485 participants) (BID) for 6 months

Outcomes

  • BSA

  • mEASI

  • EASI

  • Physician's global assessment

  • Patient's global assessment

  • Adverse events

Notes

In an additional paper (Mandelin 2010), a subgroup of 80 participants were analysed

Poole 2010 reported others outcomes of the study, quality of life, and health‐related utility analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The study sponsor generated the list, and participants were allocated by an investigator, using 1:1 stratification by centre, in the order that participants passed the selection criteria

Allocation concealment (selection bias)

Low risk

Participants were allocated by the investigator, using 1:1, stratified by centre, in the order that the participants passed the selection criteria

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The trial used identical tubes: 5 tubes for the trunk and extremities and 2 tubes for the head and neck for both groups

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The trial used identical tubes: 5 tubes for the trunk and extremities and 2 tubes for the head and neck for both groups

Incomplete outcome data (attrition bias)
All outcomes

High risk

There were 328 losses out of 972 participants. ITT analysis was done, but the method was not described

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

Sikder 2005

Methods

RCT (comparative, multicentre, open, randomised, parallel group study)

Participants

Older children (7 to 15 years) with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment BID (15 participants) compared with clobetasone butyrate 0.05% cream BID (15 participants) compared with clobetasone butyrate 0.05% cream in the morning and tacrolimus 0.03% ointment in the evening (15 participants) for 4 weeks

Outcomes

  • BSA

  • mEASI

  • Physician's global assessment

  • Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Participants were stratified by age and disease severity and randomised in parallel groups (1:1:1)

Allocation concealment (selection bias)

Unclear risk

Allocation concealment was unclear

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants were not blind because the intervention was an ointment and the control was a cream, but there was no interference with the results, as the participant's assessment was not evaluated

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding was unclear

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were no participant losses

Selective reporting (reporting bias)

Low risk

All relevant outcomes were described

Other bias

Low risk

This trial was free of other bias

AD: atopic dermatitis.
BID: twice a day.
BSA: Body Surface Area.
DLQI: Dermatology Life Quality Index.
EASI: Eczema Area and Severity Index.
IGA: Investigators' Global Assessment.
IGADA: Investigator's Global Atopic Dermatitis Assessment.
ITT: intention‐to‐treat.
LOCF: last observation carried forward.
mEASI: modified Eczema Area and Severity Index.
RCT: randomised controlled trial.
SCORAD: SCORing Atopic Dermatitis.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Arkwright 2006

This was not randomised

Chapman 2005

This study compared the intervention only with placebo. (There was no comparison with other active treatments)

del Rosso 2007

Participants in the study were treated and assessed only on a selected area of skin; whereas, this review sought studies where the whole person was treated and evaluated

Doss 2009

This study evaluated only facial eczema

Dähnhardt‐Pfeiffer 2013

This study analysed only a selected area for treatment (only lesions on the forearms); whereas, this review sought studies where the whole person was treated and evaluated

Gradman 2007

The study did not divide the different severity groups and analyse the global data; participants included mild cases, which were not of interest to this review

Granlund 2001

This study compared the intervention only with placebo. (There was no comparison with other active treatments)

Hebert 2006

The study did not divide the different severity groups and analyse the global data, including the mild cases

Hjelmgren 2007

The study was not a RCT. It was based on a RCT's data and used surveys after the treatment period to compare both groups

Ishibashi 1997

The study compared tacrolimus in the different formulations only to placebo. No comparison between the different formulations was made

Kang 2003

The study evaluated only the head and neck area

Kirsner 2010

The study did not divide the different severity groups and analyse the global data, including the mild cases

Liu 2005

The study compared the intervention only to placebo (no comparison with other active treatments)

Neumann 2008

We excluded this study because of an ineligible intervention

Onumah 2013

This was an open‐labelled pilot study on patient vehicle (ointment versus cream) preference

Rahman 2008

The study compared the intervention only to placebo. (There was no comparison with other active treatments)

Reitamo 2009

The study classified atopic dermatitis based only on body surface area and not on severity scores. We could not make classification as mild, moderate, or severe

Ruzicka 1997

The study analysed only a selected area for treatment (200 to 1000 cm²)

Schachner 2005

The study compared the intervention only with placebo. (There was no comparison with other active treatments)

Takeuchi 2012

This study used 'maintenance therapy', which was not of interest to this review. This review only investigated studies with active treatment

Torok 2003

This study did not classify disease severity

Won 2004

This was a non‐comparative study

Xhauflaire‐Uhoda 2007

Participants in this study were treated and assessed only on a selected area of skin; whereas, this review sought studies where the whole person was treated and evaluated

RCT: randomised controlled trial.

Characteristics of studies awaiting assessment [ordered by study ID]

Drake 2001

Methods

RCT (3 randomised, double‐blind, multicentre studies)

Participants

Adults and children with moderate to severe AD (Rajka and Langeland criteria (Rajka 1989))

Interventions

Tacrolimus 0.03% ointment versus tacrolimus 0.1% ointment versus vehicle (ointment base) (BID)

Outcomes

  • DLQI

  • CDLQI

  • Modified CDLQI (quality of life)

Notes

We contacted the author to identify the 3 original trials

AD: atopic dermatitis.
BID: twice a day.
DLQI: Dermatology Life Quality Index.
CDLQI: Children's Dermatology Life Quality Index.
RCT: randomised controlled trial.

Characteristics of ongoing studies [ordered by study ID]

NCT00475605

Trial name or title

APPLES: A Prospective Pediatric Longitudinal Evaluation to Assess the Long‐Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis

Methods

Observational, prospective, cohort study

Participants

People who first used tacrolimus 0.03% or 0.1% before they were 16 years of age and were treated for at least 6 weeks for the treatment of atopic dermatitis

Interventions

Topical tacrolimus 0.03% or 0.1%

Outcomes

  • The endpoint is the occurrence of serious adverse events, including the observation of systemic and cutaneous malignancies (time‐frame: at 6‐month intervals for 10 years)

Starting date

May 2005

Contact information

Notes

Each participant will be followed for 10 years in this study. ClinicalTrials.gov identifier: NCT00475605

Data and analyses

Open in table viewer
Comparison 1. Tacrolimus 0.1% versus steroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.1

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

1.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: long‐term (12 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Adverse effects: burning Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.2

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 2 Adverse effects: burning.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 2 Adverse effects: burning.

2.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: long‐term (12 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse effects: pruritus Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.3

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 3 Adverse effects: pruritus.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 3 Adverse effects: pruritus.

3.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse effects: skin infection Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.4

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 4 Adverse effects: skin infection.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 4 Adverse effects: skin infection.

4.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 SCORAD: 3 weeks Show forest plot

2

37

Mean Difference (IV, Fixed, 95% CI)

‐8.82 [‐15.36, ‐2.27]

Analysis 1.5

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 5 SCORAD: 3 weeks.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 5 SCORAD: 3 weeks.

Open in table viewer
Comparison 2. Tacrolimus 0.1% versus pimecrolimus 1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

3

543

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [1.35, 2.42]

Analysis 2.1

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

1.1 13 days

1

37

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [0.19, 19.13]

1.2 6 weeks

2

506

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [1.34, 2.42]

2 Adverse effects ‐ 6 weeks Show forest plot

2

506

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.47, 1.71]

Analysis 2.2

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 2 Adverse effects ‐ 6 weeks.

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 2 Adverse effects ‐ 6 weeks.

Open in table viewer
Comparison 3. Tacrolimus 0.03% versus steroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 3.1

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

1.1 Tacrolimus 0.03% 1x/day versus hydrocortisone acetate 1% 2x/day

1

411

Risk Ratio (M‐H, Random, 95% CI)

2.05 [1.36, 3.08]

1.2 Tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

2

790

Risk Ratio (M‐H, Random, 95% CI)

2.58 [1.96, 3.38]

1.3 Tacrolimus 0.03% 2x/day versus steroids moderate potency 2x/day

2

409

Risk Ratio (M‐H, Random, 95% CI)

0.45 [0.13, 1.57]

1.4 Tacrolimus 0.03% 2x/day versus methylprednisolone 0.03% 1x/day

1

265

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.85, 1.19]

2 Participants's assessment of global response of improvement better or much better Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 3.2

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 2 Participants's assessment of global response of improvement better or much better.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 2 Participants's assessment of global response of improvement better or much better.

2.1 Tacrolimus 0.03 1x/day versus hydrocortisone acetate 1% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Tacrolimus 0.03% 2x/day versus fluticasone 0.005% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse effects: burning Show forest plot

5

1883

Risk Ratio (M‐H, Fixed, 95% CI)

2.48 [1.96, 3.14]

Analysis 3.3

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 3 Adverse effects: burning.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 3 Adverse effects: burning.

3.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

998

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.36, 2.57]

3.2 Tacrolimus 0.03% versus steroids moderate potency

3

885

Risk Ratio (M‐H, Fixed, 95% CI)

3.52 [2.45, 5.06]

4 Adverse effects: pruritus Show forest plot

5

1883

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [1.17, 1.95]

Analysis 3.4

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 4 Adverse effects: pruritus.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 4 Adverse effects: pruritus.

4.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

998

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [1.00, 1.88]

4.2 Tacrolimus 0.03% versus steroids of moderate potency

3

885

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [1.18, 2.80]

5 Adverse effects: skin infection Show forest plot

4

1643

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.69, 1.66]

Analysis 3.5

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 5 Adverse effects: skin infection.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 5 Adverse effects: skin infection.

5.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

788

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.49, 1.79]

5.2 Tacrolimus 0.03% versus steroids of moderate potency

2

855

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.65, 2.18]

Open in table viewer
Comparison 4. Tacrolimus 0.03% versus tacrolimus 0.1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

6

1640

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.72, 0.92]

Analysis 4.1

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

1.1 3 weeks

4

985

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.96]

1.2 12 weeks

2

655

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.64, 0.99]

2 Adverse effects Show forest plot

4

986

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.86, 1.06]

Analysis 4.2

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 2 Adverse effects.

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 2 Adverse effects.

Open in table viewer
Comparison 5. Tacrolimus 0.03% versus pimecrolimus 1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 5.1

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement.

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement.

2 Adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 5.2

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 2 Adverse effects.

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 2 Adverse effects.

2.1 Application site reaction

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Burning

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Itching

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Erythema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Open in table viewer
Comparison 6. Tacrolimus 0.1% versus ciclosporin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 6.1

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 1 Adverse effects.

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 1 Adverse effects.

2 SCORAD Show forest plot

1

Mean Difference (Fixed, 95% CI)

Totals not selected

Analysis 6.2

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 2 SCORAD.

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 2 SCORAD.

2.1 14 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 21 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 28 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 35 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.5 42 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies
Figures and Tables -
Figure 2

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study
Figures and Tables -
Figure 3

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

Forest plot of comparison: 2 Tacrolimus 0.1% versus pimecrolimus 1%, outcome: 2.1 Physician's assessment of global response of improvement, clear or excellent
Figures and Tables -
Figure 4

Forest plot of comparison: 2 Tacrolimus 0.1% versus pimecrolimus 1%, outcome: 2.1 Physician's assessment of global response of improvement, clear or excellent

Forest plot of comparison: 3 Tacrolimus 0.03% versus corticosteroids, outcome: 3.1 Physician's assessment of global response of improvement, clear or excellent
Figures and Tables -
Figure 5

Forest plot of comparison: 3 Tacrolimus 0.03% versus corticosteroids, outcome: 3.1 Physician's assessment of global response of improvement, clear or excellent

Forest plot of comparison: 4 Tacrolimus 0.03% versus tacrolimus 0.1%, outcome: 4.1 Physician's assessment of global response of improvement, clear or excellent
Figures and Tables -
Figure 6

Forest plot of comparison: 4 Tacrolimus 0.03% versus tacrolimus 0.1%, outcome: 4.1 Physician's assessment of global response of improvement, clear or excellent

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 1.1

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 2 Adverse effects: burning.
Figures and Tables -
Analysis 1.2

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 2 Adverse effects: burning.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 3 Adverse effects: pruritus.
Figures and Tables -
Analysis 1.3

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 3 Adverse effects: pruritus.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 4 Adverse effects: skin infection.
Figures and Tables -
Analysis 1.4

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 4 Adverse effects: skin infection.

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 5 SCORAD: 3 weeks.
Figures and Tables -
Analysis 1.5

Comparison 1 Tacrolimus 0.1% versus steroids, Outcome 5 SCORAD: 3 weeks.

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 2.1

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 2 Adverse effects ‐ 6 weeks.
Figures and Tables -
Analysis 2.2

Comparison 2 Tacrolimus 0.1% versus pimecrolimus 1%, Outcome 2 Adverse effects ‐ 6 weeks.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 3.1

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 2 Participants's assessment of global response of improvement better or much better.
Figures and Tables -
Analysis 3.2

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 2 Participants's assessment of global response of improvement better or much better.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 3 Adverse effects: burning.
Figures and Tables -
Analysis 3.3

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 3 Adverse effects: burning.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 4 Adverse effects: pruritus.
Figures and Tables -
Analysis 3.4

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 4 Adverse effects: pruritus.

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 5 Adverse effects: skin infection.
Figures and Tables -
Analysis 3.5

Comparison 3 Tacrolimus 0.03% versus steroids, Outcome 5 Adverse effects: skin infection.

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.
Figures and Tables -
Analysis 4.1

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 1 Physician's assessment of global response of improvement, clear or excellent.

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 2 Adverse effects.
Figures and Tables -
Analysis 4.2

Comparison 4 Tacrolimus 0.03% versus tacrolimus 0.1%, Outcome 2 Adverse effects.

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement.
Figures and Tables -
Analysis 5.1

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 1 Physician's assessment of global response of improvement.

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 2 Adverse effects.
Figures and Tables -
Analysis 5.2

Comparison 5 Tacrolimus 0.03% versus pimecrolimus 1%, Outcome 2 Adverse effects.

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 1 Adverse effects.
Figures and Tables -
Analysis 6.1

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 1 Adverse effects.

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 2 SCORAD.
Figures and Tables -
Analysis 6.2

Comparison 6 Tacrolimus 0.1% versus ciclosporin, Outcome 2 SCORAD.

Summary of findings for the main comparison. Tacrolimus 0.1% compared with corticosteroids for atopic dermatitis

Tacrolimus 0.1% compared with corticosteroids for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, Europe and Canada

Intervention: tacrolimus 0.1%
Comparison: corticosteroids

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Corticosteroids

Tacrolimus 0.1%

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 3.09
(2.14 to 4.45)

371
(1 study)

⊕⊕⊕⊝
moderate¹

157 per 1000

484 per 1000
(335 to 698)

Moderate

157 per 1000

485 per 1000
(336 to 699)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 0.95
(0.78 to 1.16)

377
(1 study)

⊕⊕⊝⊝
low¹, ²

516 per 1000

490 per 1000
(403 to 599)

Moderate

516 per 1000

490 per 1000
(402 to 599)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short term (6 months)
Follow‐up: 6 months

Study population

RR 1.32
(1.17 to 1.49)

972
(1 study)

⊕⊕⊝⊝
moderate¹

464 per 1000

612 per 1000
(543 to 691)

Moderate

464 per 1000

612 per 1000
(543 to 691)

Adverse effects: burning ‐ tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 2.91
(1.6 to 5.28)

371
(1 study)

⊕⊕⊕⊝
moderate¹

70 per 1000

204 per 1000
(112 to 371)

Moderate

70 per 1000

204 per 1000
(112 to 370)

Adverse effects: burning ‐ tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks
Follow‐up: mean 3 weeks

Study population

RR 4.59
(3.1 to 6.78)

377
(1 study)

⊕⊕⊕⊝
moderate¹

129 per 1000

592 per 1000
(400 to 875)

Moderate

129 per 1000

592 per 1000
(400 to 875)

Adverse effects: burning ‐ tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: 6 months

Follow‐up: 6 months

Study population

RR 3.79

(2.99 to 4.81)

972

(1 study)

⊕⊕⊕⊝
moderate¹

138 per 1000

524 per 1000

(413 to 664)

Moderate

138 per 1000

524 per 1000

(413 to 664)

Participant's self‐assessment of global response of improvement

Follow‐up: mean 6 months

Study population

RR 1.21

(1.13 to 1.29)

974

(1 study)

⊕⊕⊝⊝
low¹, ³

718 per 1000

868 per 1000

(811 to 926)

Moderate

718 per 1000

869 per 1000

(811 to 926)

*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; RR: risk ratio.

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.

¹Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.
²Downgraded one level due to Imprecision: sample size falls below the optimal information size; 95% CI of the estimated effect includes both no effect and appreciable benefit.
³Downgraded one level due to Imprecision: sample size falls below the optimal information size.

Figures and Tables -
Summary of findings for the main comparison. Tacrolimus 0.1% compared with corticosteroids for atopic dermatitis
Summary of findings 2. Tacrolimus 0.1% compared with pimecrolimus 1% for atopic dermatitis

Tacrolimus 0.1% compared with pimecrolimus 1% for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, USA
Intervention: tacrolimus 0.1%
Comparison: pimecrolimus 1%

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Pimecrolimus 1%

Tacrolimus 0.1%

Physician's assessment of global response of improvement, clear or excellent ‐ 6 weeks
Follow‐up: mean 6 weeks

Study population

RR 1.8
(1.34 to 2.42)

506
(2 studies)

⊕⊕⊕⊝
moderate¹

202 per 1000

363 per 1000
(270 to 488)

Moderate

199 per 1000

358 per 1000
(267 to 482)

Adverse effects ‐ 6 weeks
Follow‐up: mean 6 weeks

Study population

RR 0.89
(0.47 to 1.71)

506
(2 studies)

⊕⊝⊝⊝
very low¹, ², ³

229 per 1000

204 per 1000
(108 to 392)

Moderate

227 per 1000

202 per 1000
(107 to 388)

*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; RR: risk ratio.

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.

¹Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.
²Downgraded one level due to inconsistency: there is moderate level of heterogeneity between studies: I² value of 69%.
³Downgraded one level due to imprecision: 95% CI of the estimate of summary effect includes both no effect and appreciable harm.

Figures and Tables -
Summary of findings 2. Tacrolimus 0.1% compared with pimecrolimus 1% for atopic dermatitis
Summary of findings 3. Tacrolimus 0.03% compared with corticosteroids for atopic dermatitis

Tacrolimus 0.03% compared with corticosteroids for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, Europe, Tunisia, Pakistan, Morocco, Taiwan
Intervention: tacrolimus 0.03%
Comparison: corticosteroids

Outcomes

Ilustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Corticosteroids

Tacrolimus 0.03%

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 1x/day versus hydrocortisone acetate 1% 2x/day
Follow‐up: mean 3 weeks

Study population

RR 2.05
(1.36 to 3.08)

411
(1 study)

⊕⊕⊕⊝
moderate¹

136 per 1000

279 per 1000
(185 to 419)

Moderate

136 per 1000

279 per 1000
(185 to 419)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day
Follow‐up: mean 3 weeks

Study population

RR 2.58
(1.96 to 3.38)

790
(2 studies)

⊕⊕⊕⊝
moderate¹

146 per 1000

376 per 1000
(286 to 493)

Moderate

146 per 1000

377 per 1000
(286 to 493)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 2x/day versus corticosteroids moderate‐potency 2x/day
Follow‐up: 3 to 4 weeks

Study population

RR 0.45
(0.13 to 1.57)

409
(2 studies)

⊕⊝⊝⊝
very low¹, ², ³

527 per 1000

237 per 1000
(69 to 828)

Moderate

591 per 1000

266 per 1000
(77 to 928)

Physician's assessment of global response of improvement, clear or excellent ‐ tacrolimus 0.03% 2x/day versus methylprednisolone 0.03% 1x/day
Follow‐up: mean 3 weeks

Study population

RR 1
(0.85 to 1.19)

265
(1 study)

⊕⊕⊝⊝
low¹, ³

667 per 1000

667 per 1000
(567 to 793)

Moderate

667 per 1000

667 per 1000
(567 to 794)

Adverse effects: burning ‐ tacrolimus 0.03% versus steroids

Study population

RR2.48
(1.96 to 3.14)

1883
(5 studies)

⊕⊕⊕⊕
high

89 per 1000

221 per 1000
(174 to 279)

Moderate

70 per 1000

174 per 1000
(137 to 220)

Participant's self‐assessment of global response of improvement: tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

Follow‐up: 3 weeks

Study population

RR 1.64

(1.41 to 1.90)

416

(1 study)

⊕⊕⊕⊝
moderate¹

505 per 1000

828 per 1000

(712 to 959)

Moderate

505 per 1000

828 per 1000

(712 to 959)

*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; RR: risk ratio.

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.

¹Downgraded one level due to publication bias because only very small number of studies were identified and publication bias was strongly suspected.
²Downgraded one level due to inconsistency: there is moderate level of heterogeneity between studies: I² value of 79%.
³Downgraded one level due to imprecision: 95% CI of estimated summary effect includes both no effect and appreciable harm.

Figures and Tables -
Summary of findings 3. Tacrolimus 0.03% compared with corticosteroids for atopic dermatitis
Summary of findings 4. Tacrolimus 0.03% compared with tacrolimus 0.1% for atopic dermatitis

Tacrolimus 0.03% compared with tacrolimus 0.1% for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, USA, Japan, China
Intervention: tacrolimus 0.03%
Comparison: tacrolimus 0.1%

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Tacrolimus 0.1%

Tacrolimus 0.03%

Physician's assessment of global response of improvement, clear or excellent
Follow‐up: 3 to 12 weeks

Study population

RR 0.82
(0.72 to 0.92)

1640
(6 studies)

⊕⊕⊕⊕
high

430 per 1000

353 per 1000
(310 to 396)

Moderate

445 per 1000

365 per 1000
(320 to 409)

Adverse effects
Follow‐up: mean 3 weeks

Study population

RR 0.95
(0.86 to 1.06)

986
(4 studies)

⊕⊕⊕⊝
moderate¹

573 per 1000

544 per 1000
(492 to 607)

Moderate

448 per 1000

426 per 1000
(385 to 475)

*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; RR: risk ratio.

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.

¹Downgraded one level due to imprecision: sample size is below the optimal information size.

Figures and Tables -
Summary of findings 4. Tacrolimus 0.03% compared with tacrolimus 0.1% for atopic dermatitis
Summary of findings 5. Tacrolimus 0.03% versus pimecrolimus 1% for atopic dermatitis

Tacrolimus 0.03% versus pimecrolimus 1% for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, USA
Intervention: tacrolimus 0.03% versus pimecrolimus 1%

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Tacrolimus 0.03% versus pimecrolimus 1%

Physician's assessment of global response of improvement
Follow‐up: mean 6 weeks

Study population

RR 1.42
(1.02 to 1.98)

139
(1 study)

⊕⊕⊝⊝
low¹, ²

429 per 1000

609 per 1000
(437 to 849)

Moderate

429 per 1000

609 per 1000
(438 to 849)

Adverse effects ‐ application site reaction
Follow‐up: mean 6 weeks

Study population

RR 1.07
(0.6 to 1.91)

141
(1 study)

⊕⊕⊝⊝
low², ³

239 per 1000

256 per 1000
(144 to 457)

Moderate

239 per 1000

256 per 1000
(143 to 456)

Adverse effects ‐ burning
Follow‐up: mean 6 weeks

Study population

RR 0.87
(0.43 to 1.75)

141
(1 study)

⊕⊕⊝⊝
low², ³

197 per 1000

172 per 1000
(85 to 345)

Moderate

197 per 1000

171 per 1000
(85 to 345)

Adverse effects ‐ itching
Follow‐up: mean 6 weeks

Study population

RR 2.37
(0.96 to 5.81)

141
(1 study)

⊕⊕⊝⊝
low², ³

85 per 1000

200 per 1000
(81 to 491)

Moderate

85 per 1000

201 per 1000
(82 to 494)

Adverse effects ‐ erythema
Follow‐up: mean 6 weeks

Study population

RR 2.2
(0.89 to 5.46)

141
(1 study)

⊕⊕⊝⊝
low², ³

85 per 1000

186 per 1000
(75 to 461)

Moderate

85 per 1000

187 per 1000
(76 to 464)

*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; RR: risk ratio.

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.

¹Downgraded one level due to imprecision: sample size is smaller than the optimal information size.
²Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.
³Downgraded one level due to imprecision: 95% CI of the estimate of summary effect includes both no effect and appreciable harm.

Figures and Tables -
Summary of findings 5. Tacrolimus 0.03% versus pimecrolimus 1% for atopic dermatitis
Summary of findings 6. Tacrolimus 0.1% versus ciclosporin for atopic dermatitis

Tacrolimus 0.1% versus ciclosporin for atopic dermatitis

Patient or population: people with atopic dermatitis
Settings: outpatients, Italy
Intervention: tacrolimus 0.1% versus ciclosporin

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Tacrolimus 0.1% versus ciclosporin

Adverse effects
Follow‐up: mean 6 weeks

Study population

RR 1
(0.31 to 3.28)

30
(1 study)

⊕⊝⊝⊝
very low¹, ², ³

267 per 1000

267 per 1000
(83 to 875)

Moderate

267 per 1000

267 per 1000
(83 to 876)

*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; RR: risk ratio.

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.

¹Downgraded one level due to risk of bias: randomisation and allocation concealment procedures were unclear.
²Downgraded one level due to imprecision: sample size is smaller than optimal information size; 95% CI of the estimate of summary effect includes both no effect and appreciable benefit and harm.
³Downgraded one level due to publication bias because only one study was identified and publication bias was strongly suspected.

Figures and Tables -
Summary of findings 6. Tacrolimus 0.1% versus ciclosporin for atopic dermatitis
Table 1. Characteristics of treatment and participants in included studies

Study

Number of participants

(n = 5885)

Age

Intervention

Follow up

Classification of AD

Antiga 2010

24

Adults (21 to 65 years)

Tacrolimus 0.1% ointment vs hydrocortisone butyrate 0.1% ointment (BID)

3 weeks

Moderate to severe (SCORAD)

Bieber 2007

265

Children

(2 to 15 years)

Tacrolimus 0.03% ointment (BID) vs methylprednisolone aceponate 0.1% ointment (evening) and vehicle ointment (morning)

2 to 3 weeks

Severe flare (IGA > 4) history of moderate to severe AD

Boguniewicz 1998

169

Older children

(7 to 16 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs tacrolimus 0.3% ointment vs vehicle ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Caproni 2007

16

Adults

Tacrolimus 0.1% ointment vs hydrocortisone butyrate 0.1% ointment (BID)

3 weeks

Moderate to severe (SCORAD)

Doss 2010

473

Children

(2 to 15 years)

Tacrolimus 0.03% ointment vs fluticasone 0.005% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989)) and with prior inadequate response to topical corticosteroids

Dou 2006

202

Adults (> 18 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs vehicle ointment (BID)

3 weeks

Moderate to severe

Draelos 2005

37

Adults

Tacrolimus 0.1% ointment vs pimecrolimus 1% cream (BID)

2 weeks

Moderate to severe (IGA)

Fleischer 2007

281

Adults (> = 16 years)

Tacrolimus 0.1% ointment vs pimecrolimus 1% cream (BID)

6 weeks

Moderate to severe (IGA)

Hanifin 2001

632

Adults (> = 16 years)

Tacrolimus 0.1% ointment vs tacrolimus 0.03% ointment vs vehicle ointment (BID)

3 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Hung 2007

60

Adults and

children

(9 months to 33 years)

Tacrolimus 0.03% ointment (BID) alone or with fusidic acid 2% cream vs fluticasone propionate 0.05% cream (BID) alone or with fusidic acid 2% cream

6 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Kempers 2004

141 (for safety)

139 (for efficacy)

Children (2 to 17 years)

Tacrolimus 0.03% ointment vs pimecrolimus 1% cream (BID)

6 weeks

Moderate (IGA)

Otsuki 2003

213

Children (2 to 15 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs vehicle ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Pacor 2004

30

Adults and

children (13 to 45 years)

Tacrolimus 0.1% ointment (BID) vs ciclosporin 3 mg/kg orally

6 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Paller 2001

351

Children (2 to 15 years)

Tacrolimus 0.03% ointment vs tacrolimus 0.1% ointment vs vehicle ointment (BID)

3 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Paller 2005

225

Children (2 to 15 years)

Tacrolimus 0.1% ointment vs pimecrolimus 1% cream (BID)

6 weeks

Moderate to severe (IGA)

Reitamo 2002a

570

Adults (16 to 70 years)

Tacrolimus 0.1% ointment vs tacrolimus 0.03% ointment vs hydrocortisone butyrate 0.1% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Reitamo 2002b

560

Children (2 to 15 years)

Tacrolimus 0.1% ointment vs tacrolimus 0.03% ointment vs hydrocortisone acetate 1% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Reitamo 2004

621

Children (2 to 15 years)

Tacrolimus 0.03% ointment (OD) vs tacrolimus 0.03% ointment (BID) vs hydrocortisone acetate 1% ointment (BID)

3 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

Reitamo 2005

972

Adults (> = 18 years)

Tacrolimus 0.1% ointment vs hydrocortisone butyrate 0.1% ointment (on trunk and extremities) and hydrocortisone acetate 1% ointment (on face and neck) (BID)

Up to 6 months

Moderate to severe (Rajka and Langeland (Rajka 1989))

Sikder 2005

45

Older children (7 to 15 years)

Tacrolimus 0.03% ointment (BID) vs clobetasone butyrate 0.05% cream (BID) vs clobetasone butyrate 0.05% cream (morning) and tacrolimus 0.03% ointment (evening)

4 weeks

Moderate to severe (Rajka and Langeland (Rajka 1989))

AD: atopic dermatitis.
BID: twice a day.
IGA: Investigators' Global Assessment.
OD: once daily.
SCORAD: SCORing Atopic Dermatitis.
vs: versus.

Figures and Tables -
Table 1. Characteristics of treatment and participants in included studies
Table 2. Spontaneous reported malignancies in association with topical tacrolimus use

Malignancy

Age (years)

Application site

Occurence site

Comment

Exposure to onset (days)

B‐cell lymphoma, EBV‐associated, and primary lung carcinoma

49

Face

Kidney

730

Cutaneous Kaposi sarcoma

28

Axilla, groin

Axilla, groin

HIV patient on HAART, treated for inverse psoriasis, developed KS at these sites, which metastasised, and the patient died

30

Hepatoblastoma

5

Liver

Considered unrelated

455

Lymphadenopathy – possible
lymphoma

40

Application site

Application site

Pre‐existing lymphoma lesions 'looked like' lymphoma and resolved spontaneously*

Lymphoma or Sézary syndrome

16

Face

Lymph nodes

Participant also had been on systemic ciclosporin

730

Metastatic angiosarcoma

16

Face/neck

Clavicle

Present before treatment but increased rapidly in size

105

Metastatic melanoma

39

Generalised

Metastatic disease newly detected from primary 3 years early

21 to 28

Metastatic sweat gland carcinoma

43

Not axilla

Axilla

4 years

Nodular follicular lymphoma

60

Lower limbs, face

May be associated with EBV

504

Non‐Hodgkin lymphoma

52

Used tacrolimus for 6 months. Insufficient evidence

365

Non‐Hodgkin lymphoma

54

Used tacrolimus on extensive areas: 50% of body. Died from lymphoma. Insufficient evidence

Oesophageal cancer with metastases

49

Oesophagus

122

Panniculitis‐like T‐cell lymphoma

53

Trunk, limbs

Trunk, limbs

Also used pimecrolimus

240

Squamous cell carcinoma

34

Face

Face

UV therapy, outdoor sports

Squamous cell carcinoma

57

Penis

Penis

Treated for balanitis considered to be lichen sclerosus et atrophicus; non‐specific biopsy

70

Squamous cell carcinoma

51

Mouth

Long history of pipe smoking

Squamous cell carcinoma recurrence

75

Vulva

Vulva

Treated for lichen sclerosus et atrophicus

42

T‐cell lymphoma, anaplastic large cell

50

Right hip

Right hip

Insufficient evidence

EBV: Epstein–Barr virus.
HIV: human immunodeficiency virus.
HAART: highly active antiretroviral therapy.
KS: Kaposi sarcoma.
UV: ultraviolet.
*Questionable if this should be classed as malignant.
Data shown in Ormerod 2005.

Figures and Tables -
Table 2. Spontaneous reported malignancies in association with topical tacrolimus use
Table 3. Lymphoma risk

Study

Study population

Follow‐up

Comparisons

Results related to lymphoma risks

Arellano 2007

294 cases/293,000 controls

TCIs and TCS in participants with AD

‐ Increased risk in AD participants (related to severity)

‐ No evidence of increased risk with any of the topical treatments

Arellano 2009

> 3,000,000 (cohort)

1992 to 2006

AD, treatment with topical immunosuppressants, or both

‐ Increase risk in AD participants (related to severity)

‐ Increased risk with topical corticosteroids (related to potency)

‐ Insufficient data to assess TCI‐related risks

Hui 2009

953,064 (cohort) (96% unexposed, 4% exposed)

Median 2.4 years

AD or eczema participants exposed or not to TCI

‐ Increased risk in the exposed group**

Schneeweiss 2009

‐ 118,863 for pimecrolimus

‐ 38,757 for tacrolimus

‐ 1,043,025 mid to potent corticosteroid

‐ 118,825 untreated dermatitis

‐ 118,863 for general population

2002 to 2006

(median 1.3 years)

See study population

‐ Increased risk compared with general population*

‐ No risk differences between the 3 treatments

*pre‐existing lymphomas misdiagnosed as AD.
**proportion of people who had diagnosis of AD was 2 times higher in the exposed group (i.e., there was a higher prevalence of AD than eczema in the exposed group). See Summary of main results (Risk of malignancies).
AD: atopic dermatitis.
TCI: topical calcineurin inhibitor.
TCS: topical corticosteroids.

Figures and Tables -
Table 3. Lymphoma risk
Table 4. Non‐melanoma skin cancer (NMSC) and melanoma (MM) skin cancer risk

Study

Study population

Follow up

Comparisons

Results related to skin cancer risks

Hui 2009

953,064 (cohort) (96% unexposed, 4% exposed)

Median 2.4 years

AD participants exposed or not to TCI

‐ Similar risks for NMSC

‐ Lower risks for MM

Margolis 2007

875 cases

1946 controls

Dermatitis participants (AD, seborrhoeic dermatitis, rosacea, other dermatitis) with or without use of TCI

‐ No increased risk of NMSC in TCI‐treated participants

‐ MM risk not evaluated

Naylor 2005

9813 tacrolimus‐treated participants

3 months to 4 years

AD participants with tacrolimus use compared with an aged cohort in the US

‐ No increased risk of NMSC in tacrolimus treated participants

‐ MM risk not evaluated

AD: atopic dermatitis.
TCI: topical calcineurin inhibitor.
MM: melanoma.
NMSC: non‐melanoma skin cancer.

Figures and Tables -
Table 4. Non‐melanoma skin cancer (NMSC) and melanoma (MM) skin cancer risk
Table 5. Observational non‐comparative studies

Study

1. Population

2. Age group

3. Follow‐up

Tacrolimus formulation

Common local effects

Systemic effects

Laboratory values

Malignancies

Others (number of events)

Detectable blood concentration

Gontijo 2008

1. n = 174

2. Paediatric
3. 6 weeks

0.03%

‐ Burning

‐ Pruritus

‐ Asthma (2)

‐ Pneumonia (2)

‐ Pyodermitis (1)

Koo 2005

1. n = 7923

2. Adult/paediatric

3. Median: 210 days

0.1% (92.7%)

0.03% (7.3%)

‐ Burning

‐ Pruritus

‐ Flu‐like symptoms

‐ Headache

(frequency similar to that expected of the general population)

‐ 13 cases of NMSC (no risk with calculated incidence)

‐ Alcohol intolerance 3.7%

Mandelin 2012

1. n = 50

2. Paediatric (< 2 years)

3. 2 years

0.03%

‐ Pruritus

‐ Local infection

‐ Non‐serious respiratory

infection and

gastroenteritis

< 1 ng/ml (in 98%)

Reitamo 2000

1. n = 316

2. Adults

3. 6 to 12 months

0.1%

‐ Burning

‐ Pruritus

‐ Erythema

Normal

(only 1 transient

increase in

liver enzymes)

‐ Alcohol intolerance

5 serious events:

‐ Eczema herpeticum (1)

‐ Cellulitis (1)

‐ Varicella (1)

‐ AD flare‐up (1)

Staphylococcus aureus

superinfection (1)

Minimal < 1 ng/dl in 76% of participants

Reitamo 2007

1. n = 672

2. Adults

3. 2 years

0.1%

‐ Burning

‐ Pruritus

‐ 2 cases (Bowen and prostate carcinoma) not related

‐ Benign neoplasm (7)

‐ Herpes (7%) (expected in AD participants)

‐ Eczema herpeticum (1)

‐ Erythroderma (1)

‐ AD exacerbation (1)

Reitamo 2008

1. n = 782

2. Adult/paediatric

3. 4 years (median: 1422 days)

0.1%

‐ Burning

‐ Pruritus

‐ Skin infection

‐ Flu‐like symptoms

(more in children)

6 cases

‐ Cervical carcinoma (1)

‐ Acute leukaemia (1)

‐ Chronic leukaemia (1)

‐ Basal cell carcinoma (2 to 3 on the same participant)

‐ 34 benign neoplasms

Remitz 2007

1. n = 466

2. Paediatric

3. 29.5 months (mean: 16.3 months)

0.03%

0.1%

‐ Burning

‐ Pruritus

‐ Seasonal infection

(flu‐syndrome)

‐ No growth

retardation

Normal

‐ Leukopenia (1)*

‐ Herpes (4.9%)/eczema herpeticum (0.9%)

‐ Molluscum 3%)

‐ Warts (3.6%)

Saple 2003

1. n = 125

2. 12 to 69 years

3. 5 weeks

0.03%

‐ Burning

‐ Pruritus

‐ Erythema

Normal

Won 2004

1. n = 18

2. Adult/paediatric

3. 4 weeks

0.03%

‐ Burning

‐ Pruritus

Normal

Serious events (3):

‐ Flu‐syndrome (1)

‐ Severe skin rash (1)

‐ Eczema herpeticum (1)

Wong 2003

1. n = 30

2. Adult/paediatric

3. 4 weeks

0.1% adults

0.03% paediatric

‐ Burning

‐ Pruritus

Normal

2 participants

< 5 ng/ml

* 6‐year‐old participant, at month 6, resolution after withdrawn.
AD: atopic dermatitis.
NMSC: non‐melanoma skin cancer.

Figures and Tables -
Table 5. Observational non‐comparative studies
Comparison 1. Tacrolimus 0.1% versus steroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: long‐term (12 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Adverse effects: burning Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: long‐term (12 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse effects: pruritus Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse effects: skin infection Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4.1 Tacrolimus 0.1% versus hydrocortisone acetate 0.1%: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Tacrolimus 0.1% versus hydrocortisone butyrate: 3 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Tacrolimus 0.1% versus hydrocortisone acetate and butyrate 0.1%: short‐term (6 months)

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 SCORAD: 3 weeks Show forest plot

2

37

Mean Difference (IV, Fixed, 95% CI)

‐8.82 [‐15.36, ‐2.27]

Figures and Tables -
Comparison 1. Tacrolimus 0.1% versus steroids
Comparison 2. Tacrolimus 0.1% versus pimecrolimus 1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

3

543

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [1.35, 2.42]

1.1 13 days

1

37

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [0.19, 19.13]

1.2 6 weeks

2

506

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [1.34, 2.42]

2 Adverse effects ‐ 6 weeks Show forest plot

2

506

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.47, 1.71]

Figures and Tables -
Comparison 2. Tacrolimus 0.1% versus pimecrolimus 1%
Comparison 3. Tacrolimus 0.03% versus steroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Tacrolimus 0.03% 1x/day versus hydrocortisone acetate 1% 2x/day

1

411

Risk Ratio (M‐H, Random, 95% CI)

2.05 [1.36, 3.08]

1.2 Tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

2

790

Risk Ratio (M‐H, Random, 95% CI)

2.58 [1.96, 3.38]

1.3 Tacrolimus 0.03% 2x/day versus steroids moderate potency 2x/day

2

409

Risk Ratio (M‐H, Random, 95% CI)

0.45 [0.13, 1.57]

1.4 Tacrolimus 0.03% 2x/day versus methylprednisolone 0.03% 1x/day

1

265

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.85, 1.19]

2 Participants's assessment of global response of improvement better or much better Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Tacrolimus 0.03 1x/day versus hydrocortisone acetate 1% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Tacrolimus 0.03% 2x/day versus hydrocortisone acetate 1% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Tacrolimus 0.03% 2x/day versus fluticasone 0.005% 2x/day

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse effects: burning Show forest plot

5

1883

Risk Ratio (M‐H, Fixed, 95% CI)

2.48 [1.96, 3.14]

3.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

998

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.36, 2.57]

3.2 Tacrolimus 0.03% versus steroids moderate potency

3

885

Risk Ratio (M‐H, Fixed, 95% CI)

3.52 [2.45, 5.06]

4 Adverse effects: pruritus Show forest plot

5

1883

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [1.17, 1.95]

4.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

998

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [1.00, 1.88]

4.2 Tacrolimus 0.03% versus steroids of moderate potency

3

885

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [1.18, 2.80]

5 Adverse effects: skin infection Show forest plot

4

1643

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.69, 1.66]

5.1 Tacrolimus 0.03% versus hydrocortisone acetate 1%

2

788

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.49, 1.79]

5.2 Tacrolimus 0.03% versus steroids of moderate potency

2

855

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.65, 2.18]

Figures and Tables -
Comparison 3. Tacrolimus 0.03% versus steroids
Comparison 4. Tacrolimus 0.03% versus tacrolimus 0.1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement, clear or excellent Show forest plot

6

1640

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.72, 0.92]

1.1 3 weeks

4

985

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.96]

1.2 12 weeks

2

655

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.64, 0.99]

2 Adverse effects Show forest plot

4

986

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.86, 1.06]

Figures and Tables -
Comparison 4. Tacrolimus 0.03% versus tacrolimus 0.1%
Comparison 5. Tacrolimus 0.03% versus pimecrolimus 1%

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Physician's assessment of global response of improvement Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 Adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Application site reaction

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 Burning

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 Itching

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Erythema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 5. Tacrolimus 0.03% versus pimecrolimus 1%
Comparison 6. Tacrolimus 0.1% versus ciclosporin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Adverse effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 SCORAD Show forest plot

1

Mean Difference (Fixed, 95% CI)

Totals not selected

2.1 14 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 21 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 28 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 35 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

2.5 42 days

1

Mean Difference (Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 6. Tacrolimus 0.1% versus ciclosporin