Dehydroepiandrosterone for systemic lupus erythematosus

David Crosbie; Corri Black; Linda McIntyre; Pamela Royle; Sian Thomas

doi:10.1002/14651858.CD005114.pub2

Deshidroepiandrosterona para el lupus eritematoso sistémico

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Referencias

Referencias de los estudios incluidos en esta revisión

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estudios excluidos
otras referencias

Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild‐to‐moderate systemic lupus erythematosus: a multicenter randomized, double‐blind, placebo‐controlled trial. Arthritis and Rheumatism 2002;46(11):2924‐7.

Hartkamp A, Geenen R, Godaert GL, Bijl M, Bijlsma JW, Derksen RH. The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus. Arthritis and Rheumatism 2004;50(11):3591‐5.

Nordmark G, Bengtsson C, Larsson A, Karlsson FA, Sturfelt G, Ronnblom L. Effects of dehydroepiandrosterone supplement on health‐related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity 2005;38(7):531‐40.

Petri MA, Lahita RG, Van Vollenhoven RF, Merrill JT, Schiff M, Ginzler EM, Strand V, Kunz A, Gorelick KJ, Schwartz KE, ‐Study‐Group. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double‐blind, randomized, placebo‐controlled trial. Arthritis and Rheumatism 2002;46(7):1820‐9.

Mease PJ, Ginzler EM, Gluck OS, Schiff M, Goldman A, Greenwald M, Cohen S, Egan R, Quarles BJ, Schwartz KE. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. Journal of Rheumatology 2005;32(4):616‐21.

Google Scholar

Petri MA, Mease PJ, Merrill JT, Lahita RG, Iannini MJ, Yocum DE, Ginzler EM, Katz RS, Gluck OS, Genovese MC, Van Vollenhoven R, Kalunian KC, Manzi S, Greenwald MW, Buyon JP, Olsen NJ, Schiff MH, Kavanaugh AF, Caldwell JR, Ramsey‐Goldman R, St Clair EW, Goldman AL, Egan RM, Polisson RP, Moder KG, Rothfield NF, Spencer RT, Hobbs K, Fessler BJ, Calabrese LH, Moreland LW, Cohen SB, Quarles BJ, Strand V, Gurwith M, Schwartz KE. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis and Rheumatism 2004;50(9):2858‐68.

Van Vollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double‐blind, placebo‐controlled, randomized clinical trial. Arthritis and Rheumatism 1995;38(12):1826‐1831.

vanVollenhoven RF, Engleman EG, Lambert RE, Lee YSL, McGuire JL. Treatment of Systemic Lupus‐Erythematosus with Dehydroepiandrosterone ‐ Interim Analysis of A Double‐Blinded, Randomized, Placebo‐Controlled, Clinical‐Trial. Arthritis and Rheumatism 1993;36(9 Suppl S Sep):S92.

Google Scholar

vanVollenhoven RF, Lambert RE, Lee YSL, McGuire JL, Engleman EG. Treatment of Systemic Lupus‐Erythematosus with Dehydroepiandrosterone Follow‐Up from An Open‐Label Clinical‐ Trial. Arthritis and Rheumatism 1993;36(9 Suppl S):S228.

Google Scholar

Van Vollenhoven RF, Park JL, Genovese MC, West JP, McGuire JL. A double‐blind, placebo‐controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus. Lupus 1999;8(3):181‐187.

Referencias de los estudios excluidos de esta revisión

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otras referencias

Barry NN, McGuire JL, Van Vollenhoven RF. Dehydroepiandrosterone in systemic lupus erythematosus: Relationship between dosage, serum levels, and clinical response. Journal of Rheumatology 1998;25(12):2352‐6.

Google Scholar

Chang DM, Chu SJ, Chen HC, Kuo SY, Lai JH. Dehydroepiandrosterone suppresses interleukin 10 synthesis in women with systemic lupus erythematosus. Annals of Rheumatic Diseases 2004;63(12):1623‐6.

van Vollenhoven RF, Lee YSL, Lambert RE, Engleman EG, Mcdevitt HO, McGuire JL. Treatment of Systemic Lupus‐Erythematosus with Dehydroepiandrosterone ‐ A Pilot‐Study. Arthritis and Rheumatism 1992;35(9 Suppl S):S55.

Google Scholar

van Vollenhoven RF, Lambert RE, Lee YSL, McGuire JL, Engleman EG. Treatment of Systemic Lupus‐Erythematosus with Dehydroepiandrosterone Follow‐Up from An Open‐Label Clinical‐ Trial. Arthritis and Rheumatism 1993;36(9 Suppl S):S228.

Google Scholar

Van Vollenhoven RF, Engleman EG, McGuire JL. An open study of dehydroepiandrosterone in systemic lupus erythematosus. Arthritis and Rheumatism 1994;37(9):1305‐10.

van Vollenhoven RF. Increased bone mineral density in patients with SLE treated with DHEA. Arthritis and Rheumatism 1996;39(9 Suppl S Sep):1588.

van Vollenhoven RF. Dehydroepiandrosterone improves cognitive function in patients with systemic lupus erythematosus: Results of a double‐blinded, placebo controlled pilot study. Lupus 2001;10(Supplement 1):S51.

Google Scholar

Van Vollenhoven R, Morabito L, Engleman E, Lambert R, Lee Y, S, McGuire J, L. Treatment of systemic lupus erythematosus with dehydroepiandrosterone, two‐year follow‐up from an open‐label clinical trial. Arthritis and Rheumatism 1994;37(9 SUPPL.):S407.

Google Scholar

Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos

Boumpas DT, Austin HA, Vaughn E, Klippel JH, Steinberg AD, Yarboro CH, Barlow JE. Controlled Trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992;340:741‐5. [MEDLINE: 54]

Caccavo D, Lagana B, Mitterhofer AP, Ferri GM, Afeltra A, Amoroso A, Bonomo L. Long‐term treatment of systemic lupus erythematosus with cyclosporin A. Arthritis and Rheumatism 1997;40:27‐35.

Dr Chris Cates. EBM Website. www.nntonline.net2003.

Google Scholar

Center for Drug Evaluation and Research (CDER). Guidance for Industry: Systemic Lupus Erythematosus ‐ Developing Drugs for Treatment. U.S. Department of Health and Human Services UFood and Drug Administration, U.S. Department of Health and Human Services. U.S. Department of Health and Human Services, 2005.

Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulphate in systemic lupus erythematosus. New England Journal of Medicine 1991;324:150‐4. [MEDLINE: 51]

Enlace al artículo

Derksen RHWM. Dehydroepiandrosterone (DHEA) and systemic lupus erythematosus. Seminars in Arthritis and Rheumatism 1998;27:335‐47. [MEDLINE: 63]

FitzGerald JD, Grossman JM. Validity and reliability of retrospective assessment of disease activity and flare in observational cohorts of lupus patients. Lupus 1999;8(8):638‐44.

Genelabs Technologies I. GL701 (DHEA, prasterone) for the treatment of systemic lupus erythematosus (SLE) in women. Briefing Document FDA Arthritis Advisory Committee. Briefing Document, FDA Arthritis Advisory Committee 2001; Vol. Briefing Document, FDA Arthritis Advisory Committee. [MEDLINE: 64]

Google Scholar

Hart HH, Grigor RR, Caughey DE. Ethnic difference in the prevalence of systemic lupus erythematosus. Annals of Rheumatic Diseases 1983;42(5):529‐32.

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 [updated September 2006]. In: The Cochrane Library, Issue 4, 2006. John Wiley & Sons, Ltd. Chichester, UK.

Homik J, Cranney A, Shea B, Tugwell P, Wells G, Adachi R, Suarez‐Almazor M. Bisphosphonates for steroid induced osteoporosis. Cochrane Database of Systematic Reviews 1999, Issue 1. [MEDLINE: 53]

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17(1):1‐12.

Johnson AE, Gordon C, Palmer RG, Baethge BA. The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis and Rheumatism 1995;38(4):551‐8. [MEDLINE: 61]

Johnson AE, Gordon C, Hobbs FDR, Baethge BA. Undiagnsoed systemic lupus erythematosus in the community. Lancet 1996;347:367‐9. [MEDLINE: 62]

Khan KS, ter Riet G, Glanville J, Sowden A, Kleijnen J. Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out and commissioning reviews. CRD Report 4 (2nd edition) 2000; Vol. CRD Report 4 (2nd edition).

Google Scholar

Kingdon EJ, McLean AG, Psimenou E, Davenport A, Powis SH, Sweny P, Burns A. The safety and efficacy of MMF in lupus nephritis: a pilot study. Lupus 2001;10(9):606‐11.

Lee SS, Li CS, Li PCK. Clinical profile of Chinese patients with systemic lupus erythematosis. Lupus 1993;2:105‐9. [MEDLINE: 48]

McCarty DJ, Manzi S, Medsger TA, Ramsey‐Goldman R, LaPorte RE, Kwoh CK. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis and Rheumatism 1995;38(9):1260‐70.

Mok CC, Lau CS. Lupus in Hong Kong Chinese. Lupus 2003;12(9):717‐22.

Nived O, Sturfelt G. In: Isenberg D.A, Tucker L.B editor(s). Does the Black population in Africa get SLE? If not why not. London: Martin Dunitz Ltd, 1997. [MEDLINE: 47]

Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, Lockshin M, Merrill JT, Belmont HM, Askanase AD, McCune WJ, Hearth‐Holmes M, Dooley MA, Von Feldt J, Friedman A, Tan M, Davis J, Cronin M, Diamond B, Mackay M, Sigler L, Fillius M, Rupel A, Licciardi F, Buyon JP. Combined oral contraceptives in women with systemic lupus erythematosus. New England Journal of Medicine 2005;353(24):2550‐8.

Ruiz‐Irastorza G, Khamashta MA, Castellino G, Hughes GR. Systemic Lupus Erythematosus. Lancet. 357 2001; Vol. 357:1027‐32. [MEDLINE: 65]

Google Scholar

Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12.

Silman A, Shipley M. Opthalmological monitoring for hydroxychloroquire toxicity: a scientific review of the available data. British Journal of Rheumatology 1997;36:599‐601. [MEDLINE: 52]

Singh G, Triadafilopoulos G. Epidemiology of NSAUD‐induced gastrointestinal complications. Journal of Rheumatology 1999;26(Suppl 56):18‐24. [MEDLINE: 49]

Google Scholar

Strand V, Gladman D, Isenberg D, Petri M, Smolen J, Tugwell P. Outcome measures to be used in clinical trials in systemic lupus erythematosus. Journal of Rheumatology 1999;26(2):490‐7.

Google Scholar

Strand V. Biologic agents and innovative interventional approaches in the management of systemic lupus erythematosus. Current Opinion in Rheumatology 1999;11(5):330‐40. [MEDLINE: 35]

Strand V. Clinical trial design in systemic lupus erythematosus: lessons learned and future directions. Lupus 2004;13(5):406‐11. [MEDLINE: 59]

Tugwell P, Shea B, Boers M, Brooks P, Simon L, Strand V, Wells G (Editors). Evidence‐based Rheumatology. London: BMJ Books, 2004.

Whelton A. Renal and related cardiovascular effects of conventional and COX‐2‐specific NSAIDs and non‐NSAID analgesia. American Journal of Therapeutics 2000;7:63‐74. [MEDLINE: 50]

Wollaston SJ, Farewell VT, Isenberg DA, Gordon C, Merrill JT, Petri MA, Kalunian KC. Defining response in systemic lupus erythematosus: a study by the Systemic Lupus International Collaborating Clinics group. Journal of Rheumatology 2004;31(12):2390‐4.

Google Scholar

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Chang 2002

Methods	double blind RCT 6 months
Participants	Total: 120 Sex: female Ethnicity: Chinese Median age: not stated Inclusion criteria:active SLE (including SLEDAI > 2), on <10mg prednisolone Exclusion criteria:other immunosuppressants
Interventions	Grp 1: DHEA 200mg/dy Grp 2: placebo
Outcomes	Stated primary: SLAM SLEDAI, HRQoL, flares
Notes	Funding: Genelabs + National Science Council
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Hartkamp 2004

Methods	Double blind, controlled trial (Probably randomised but does not specify) 12 months
Participants	Total: 60 Sex: female Ethnicity: 82‐93% Caucasian Median age: 41‐45 years Inclusion criteria: quiescent SLE, on <10mg prednisolone Exclusion criteria: nil else
Interventions	Grp 1: DHEA 200mg/dy Grp 2: placebo
Outcomes	Stated primary: Wellbeing and fatigue (not reported) SLEDAI, Bone mineral density
Notes	Funding: Dutch Arthritis Association
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Nordmark 2005

Methods	Double blind RCT 6 months (open label continuation for further 6 months)
Participants	Total: 37* (4 dropped out and not included in analysis, 41 recruited) Sex: female Ethnicity: not stated Mean age: 47 to 48 years (selection involved stratification into 2 age group of equal size)
Interventions	Grp 1: DHEA 20‐30mg/dy Grp 2: placebo
Outcomes	Stated primary: HRQoL and behaviour (various tools) SLEDAI; SLICC; Bone mineral density; biological markers;
Notes	Funding: various non industry sources
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Petri 2002

Methods	double blind RCT 7‐9 months
Participants	Total: 191 Sex: female Ethnicity: 55‐57% Caucasian; 25‐27% African‐American Median age: 30‐41yr Inclusion criteria: >10mg prednisolone for 12mths Exclusion criteria: other immunosuppressants
Interventions	Grp 1: DHEA 100mg/dy Grp 2: DHEA 200mg/dy Grp 3: placebo
Outcomes	Stated primary: 'Responder' days of prednisolone <7.5mg SLEDAI (not reported), HRQoL (not reported), Fatigue, (not reported), SLICC (not reported) biological markers
Notes	Funding: Genelabs Technologies Inc
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Petri 2004

Methods	double blind RCT 12 months
Participants	Total: 381 Sex: female Ethnicity:71‐77% Caucasian Median age:44 years Inclusion criteria: active SLE Exclusion criteria:
Interventions	Grp 1: DHEA 200mg/dy Grp 2: placebo
Outcomes	Stated primary: "responders" on composite score SLEDAI, HRQoL, flares, SLAM, fatigue (BMD in subgroup)
Notes	Funding: Genelabs Technologies Inc
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Van Vollenhoven 1995

Methods	double blind RCT 3 months
Participants	Total: 28* (2 dropped out before study started and not included in analysis ‐ 30 recruited) Sex: female Ethnicity: 64‐79% Caucasian; 21‐36% other Median age: 35‐40 years Inclusion criteria: mild to moderate SLE Exclusion criteria: renal disease, high dose steroids or other immunosuppressants
Interventions	Grp 1: DHEA 100mg/dy Grp 2: placebo
Outcomes	Stated primary: not stated SLEDAI, prednisolone dose, HRQoL, Physician global VAS, flares, other biochemical markers
Notes	Funding: Northern California Arthritis Foundation
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Van Vollenhoven 1999

Methods	double blind RCT 6 months
Participants	Total: 19 Sex: male or female (only 3 male) Ethnicity: 33‐40% Caucasian; 11‐20% African‐American; 40‐44% other Median age:35‐39 yr Inclusion criteria: severe SLE Exclusion criteria:
Interventions	Grp 1: DHEA 200mg/dy Grp 2: placebo
Outcomes	Stated primary: stabilise major lupus manifestation SLEDAI, SLAM, HRQoL, renal proteinuria, biological SLEDAI, Prednisolone dose, Patient global VAS, Physician global VAS, Bone mineral density, other biochemical markers
Notes	Funding: NIH grant
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

HRQoL ‐ health related quality of life including SF36 and Patient Visual analogue scores

Characteristics of excluded studies [ordered by study ID]

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estudios incluidos

Study	Reason for exclusion
Barry 1998	Case series; no control group
Chang 2004	Outcome measure not included in this review
van Vollenhoven 1992	Case series; no control group
van Vollenhoven 1993	Case series; no control group
van Vollenhoven 1994	Case series; no control group
van Vollenhoven 1996	Case series; no control group
van Vollenhoven 2001	Study less than 3 months duration; placebo controlled trial
vanVollenhoven 1994b	Case series; no control group

Data and analyses

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Comparison 1. Disease Activity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SLEDAI Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 Disease Activity, Outcome 1 SLEDAI.
1.1 Mild to moderate SLE	2	148	Mean Difference (IV, Fixed, 95% CI)	‐0.61 [‐2.12, 0.89]
1.2 Severe SLE	1	19	Mean Difference (IV, Fixed, 95% CI)	‐6.4 [‐13.12, 0.32]

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Comparison 2. Quality of Life

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Patient Global Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 Quality of Life, Outcome 1 Patient Global.
1.1 Mild to Moderate SLE	2	148	Mean Difference (IV, Fixed, 95% CI)	‐11.46 [‐19.08, ‐3.84]
1.2 Severe SLE	1	19	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐3.67, 3.27]
2 Physician Global Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 Quality of Life, Outcome 2 Physician Global.
2.1 Mild to moderate SLE	2	148	Mean Difference (IV, Fixed, 95% CI)	‐3.16 [‐8.12, 1.80]
2.2 Severe SLE	1	19	Mean Difference (IV, Fixed, 95% CI)	‐9.80 [‐40.36, 20.76]

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Comparison 3. Adverse events

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Acne Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.1 Comparison 3 Adverse events, Outcome 1 Acne.
1.1 Mild to moderate SLE	4	657	Risk Ratio (M‐H, Fixed, 95% CI)	2.16 [1.65, 2.83]
1.2 Severe SLE	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.68, 5.85]
2 Hirsutism Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.2 Comparison 3 Adverse events, Outcome 2 Hirsutism.
2.1 Mild to moderate SLE	4		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Severe SLE	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Menstrual change Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.3 Comparison 3 Adverse events, Outcome 3 Menstrual change.
3.1 Mild to moderate SLE	3	276	Risk Ratio (M‐H, Fixed, 95% CI)	1.2 [0.38, 3.77]
3.2 Severe SLE	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	2.67 [0.98, 7.22]

Analysis 1.1

Comparison 1 Disease Activity, Outcome 1 SLEDAI.

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Analysis 2.1

Comparison 2 Quality of Life, Outcome 1 Patient Global.

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Analysis 2.2

Comparison 2 Quality of Life, Outcome 2 Physician Global.

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Analysis 3.1

Comparison 3 Adverse events, Outcome 1 Acne.

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Analysis 3.2

Comparison 3 Adverse events, Outcome 2 Hirsutism.

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Analysis 3.3

Comparison 3 Adverse events, Outcome 3 Menstrual change.

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Table 1. Summary of quality assessment of included studies

Study id	Assignment	Alloc concealment	Baseline	ITT	Dropouts	Outcome Blind
Chang 2002	Yes	Probably Adequate	No detail presented	Yes	Yes (7/120)	Yes
Hartkamp 2004	Unclear	Adequate	No (postmenopausal status higher in active arm; oestrogen use lower in active arm)	No (2 declined final dexa scan excluded	Yes (2/60)	Yes
Nordmark 2005	Unclear	Unclear	Similar (DHEA treatment group had slightly more active disease	Unclear	Yes (3/41)	Yes
Petri 2002	Unclear	Probably Adequate	Yes	Yes	No (49/191)	Yes
Petri 2004	yes	Adequate	yes (although Anti dsDNA higher in active treatment group)	Yes	Yes (115/381)	Yes
Van Vollenhoven 1995	Unclear	Unclear	Yes	No	Yes (2/28)	Yes
Van Vollenhoven 1999	Yes	Probably Adequate	No Males in placebo group only, organs effected differed.Some differences in baseline activity scores with DHEA group tending to be higher (none statistically significant)	No	Yes (2/21)	Yes
KEY	Assignment random	Allocation concealed	Baseline characteristics similar	Intention to treat analysis	drop outs described	Outcomes blinded

Table 1. Summary of quality assessment of included studies

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Table 2. Summary of Disease activity: SLEDAI (0‐105) (individual studies)

Study	no. participants	placebo (SEM)	DHEA (SEM)	change vs placebo
Mild/Moderate
Chang 2002*	Placebo: 59; DHEA 61	‐1.4 (4.6)	‐1.2 (5.4)	p=0.7
Hartkamp 2004	Placebo: 30; DHEA 30	+0.3 (na)	+0.43 (na)	p=0.79
Nordmark 2005	Placebo: 17 DHEA 20			reported as "no significant change"
Petri 2002	Placebo 64; DHEA 100 63; DHEA 200 64			measured but not reported for all participants
Petri 2004	Placebo: 192 (146 reported) DHEA 189 (147 reported)	17.8% deteriorated	9.5% deteriorated	p=0.04 not reported for all participants ‐ only those with "active disease"
van Vollenhoven 1995*	Placebo: 14 DHEA 14	+0.79 (0.75)	‐1.71 (1.18)	p=0.09
*Summarised in Meta‐analysis

Severe
van Vollenhoven 1999*	Placebo: 10 DHEA 9	‐3.9 (1.4)	‐10.3 (3.1)	p=0.07
*Summarised in Meta‐analysis

Table 2. Summary of Disease activity: SLEDAI (0‐105) (individual studies)

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Table 3. Summary of Disease activity: SLAM (0‐84) (individual studies)

Study	No. participants	placebo (SEM)	DHEA (SEM)	change vs. placebo
Mild/Moderate Disease at baseline
Chang 2002*	Placebo: 59; DHEA 61	‐2.0 (0.49)	‐2.6 (0.44)	p=0.355
Petri 2004	Placebo: 192 (146 reported) DHEA 189 (147 reported)	10.3% deteriorated	6.8% deteriorated	p= 0.29 Not reported for all participants ‐ only those with "active disease"

Severe disease at baseline
van Vollenhoven 1999	Placebo: 10 DHEA: 9	‐2.4 (2.0)	‐5.4 (2.34)	p=0.41

Table 3. Summary of Disease activity: SLAM (0‐84) (individual studies)

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Table 4. Summary of Health Related Quality of Life: Patient Global (0‐100) (ind.studies)

study	No. Participants	placebo (SEM)	DHEA (SEM)	change vs. placebo
Mild to Moderate disease
Chang 2002	Placebo 59: DHEA 61	+5.4 (2.56)	‐5.5 (3.46)	p=0.005 (adjusted for treat centre and treatment, no unadjusted presented) [95% CI from crude analysis ‐76.1 to 54.3]
Hartkamp 2004	Placebo 30: DHEA 30			measured but not reported
Nordmark 2005	Placebo 17: DHEA 20			not measured
Petri 2002	Placebo 64: DHEA 100mg 62: DHEA 200mg 64			measured but not reported
Petri 2004	Placebo 192 (reported 146): DHEA 189 (reported 147)	22.6% deteriorated	10.9% deteriorated	p=0.007 Not reported for all participants, only those with "active disease"
van Vollenhoven 1995	Placebo 14: DHEA 14	+2.4 (7.0)	‐11.5 (5.7)	unadjusted 0.138, P vs placebo adjusted 0.022
*Summarised in Meta‐analysis

Severe Disease
van Vollenhoven 1999	Placebo 10: DHEA 9	‐23.5 (2.4)	‐23.7 (4.8)	p= 0.53

Table 4. Summary of Health Related Quality of Life: Patient Global (0‐100) (ind.studies)

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Table 5. Adverse events

Adverse events	Chang 2002	Hartkamp 2004	Petri 2002	Petri 2004	van Vollenhoven 1995	van Vollenhoven 1999	Nordmark 1002
No. Participants	DHEA:61; Placebo:59	DHEA:30; Placebo:30	DHEA 100mg:63; DHEA 200mg: 64; Placebo:64	DHEA:192; Placebo: 189	DHEA:14; Placebo:14	DHEA:10; Placebo:10	DHEA: 20; Placebo:17
Serious AEs	DHEA: 7 (11.5); Placebo: 18 (30.5)			DHEA: 33 (17); placebo: 27 (14)	DHEA: 1; placebo: 1	DHEA: 1; placebo: 2
Withdrawal due to AE			DHEA 100: 4 (6); DHEA 200: 6 (9); placebo:3 (5)	DHEA: 11 (5.7); placebo:27 (14.3)	DHEA: 0; placebo: 0
Acne	DHEA: 59%; placebo: 29%		DHEA 100: 26 (41); DHEA 200: 26 (41); placebo:12 (19)	DHEA: 63 (33.3); placebo: 27 (14.1)	DHEA:8 (57); placebo: 1 (7)	DHEA: 6; placebo:3
Hirsutism			DHEA 100: 7 (11); DHEA 200:5 (7.8); placebo: 3 (4.7)	DHEA: 31 (16.4); placebo: 3 (1.6)	DHEA: 2 (14); placebo:4 (28)	DHEA:4; placebo:2
Weight Gai					DHEA: 2(14); placebo:1 (7)
Rash			DHEA 100: 3 (4.8); DHEA 200: 7 (11); placebo: 3 (4.7)	DHEA: 62 (32.3); placebo: 75 (39.7)	DHEA :0 ; placebo: 2 (14)
Menarrhagia			DHEA 100:5 (7.9); DHEA 200: 5 (7.8); placebo: 3 (4.7)		DHEA: 1 (7); placebo: 2 (14)	DHEA: 8; placebo :3
Headache			DHEA 100: 3 (4.8); DHEA 200: 4 (6.3); placebo:1 (1.6)	DHEA: 56 (29.2); placebo:42 (22.2)		DHEA:4 ; placebo: 4
Abdominal Pain			DHEA 100: 3 (4.8); DHEA 200: 5 (7.8); placebo:0	DHEA: 30 (25.6); placebo: 27 (14.3)
Chest Pain				DHEA: 22 (10.4); placebo: 14 (7.4)
Arthralgia				DHEA:71 (37.0); placebo: 68 (36)
Asthenia			DHEA 100: 4 (6.3); DHEA 200: 3 (4.7); placebo:3 (4.7)	DHEA: 51 (26.6); Placebo45 (23.8)
Myalgia				DHEA: 69 (35.9); placebo: 42 (22.2)
flu like symptoms				DHEA: 42 (21.9); placebo: 39 (20.6)
Stomatitis				DHEA: 44 (22.9); placebo: 28 (14.8)
Mood Change				DHEA: 30 (15.6); placebo:28 (14.8)	DHEA; 1 (7); placebo: 0	DHEA:1; placebo:3
Alopecia				DHEA: 39 (20.3); placebo: 28 (14.8)		DHEA: 0; placebo:1
Fever				DHEA: 28 (14.6); placebo: 22 (11.6)
Perihperal vascular disease				DHEA: 20 (10.4); placebo: 19 (10.1)
Sinusitis				DHEA: 21 (10.4); placebo: 17 (9)
Insomnia			DHEA 100: 4 (6.3); DHEA 200: 3 (4.7); placebo:2 (3.1)			DHEA: 2; placebo:1

Table 5. Adverse events

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Table 6. Clinical Relevance Table ‐ Summary of Meta‐analysis: Benefits

Outcome	# patients(# trials)	Control baseline m	Wt absolute change	Relative % change	NNT (B) or NNT (H)	Statistical Sig	Quality of Evidence
SLEDAI (mild/moderate) (0‐105)	148(2)	6.55*	0.6% reduction (0.6 points less on a scale of 0‐105)	9.3% improvement	NA	not statistically significant	Gold
95% confidence interval			‐2.12 to 0.89
SLEDAI (severe) (0‐105)	19(1)	9.4	6% reduction (6.4 points less on a scale of 0‐105)	68% improvement	3	borderline statistically significant	Silver
95% confidence interval			‐13.12 to 0.32
HRQoL (mild/moderate) Patient Global (0‐100)	148 (2)	28.5	11.5% reduction (11.5 point reduction on a scale of 0‐100)	40.4% improvement	5	statistically significant	Gold
95% confidence interval			‐19.1 to ‐3.8
HRQoL (severe) (0‐100)	19 (1)	52.6	0.2% reduction (0.2 point reduction on a scale of 0‐100)	0.4% improvement	NA	not statistically significant	Silver
95% confidence interval			‐3.7 to 3.3
Legend:	SLEDAI ‐ SLE disease activity index HRQOL ‐ Health Related Quality of Life				NA=not applicable

Table 6. Clinical Relevance Table ‐ Summary of Meta‐analysis: Benefits

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Table 7. Clinical Relevance Table: Summary Meta‐analysis table: adverse events

Outcome	# patients (#trials)	Event rate (placebo)	Event rate (treated)	Relative risk	Absolute risk dif	NNH
Adverse Events (mild/moderate): Acne	657 (4)	56/326 (17.2%)	123/331 (37.2%)	2.2	0.2	5
95% confidence interval				1.65 to 2.83	0.13 to 0.26
Adverse Events (mild/moderate): Menstrual Change	276 (3)	5/137 (3.6%)	6/139 (4.3%)	1.2	0.1	not statistically significant
95% confidence interval				0.38 to 3.77	‐0.04 to 0.05

Table 7. Clinical Relevance Table: Summary Meta‐analysis table: adverse events

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Comparison 1. Disease Activity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SLEDAI Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 Mild to moderate SLE	2	148	Mean Difference (IV, Fixed, 95% CI)	‐0.61 [‐2.12, 0.89]
1.2 Severe SLE	1	19	Mean Difference (IV, Fixed, 95% CI)	‐6.4 [‐13.12, 0.32]

Comparison 1. Disease Activity

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Comparison 2. Quality of Life

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Patient Global Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 Mild to Moderate SLE	2	148	Mean Difference (IV, Fixed, 95% CI)	‐11.46 [‐19.08, ‐3.84]
1.2 Severe SLE	1	19	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐3.67, 3.27]
2 Physician Global Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 Mild to moderate SLE	2	148	Mean Difference (IV, Fixed, 95% CI)	‐3.16 [‐8.12, 1.80]
2.2 Severe SLE	1	19	Mean Difference (IV, Fixed, 95% CI)	‐9.80 [‐40.36, 20.76]

Comparison 2. Quality of Life

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Comparison 3. Adverse events

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Acne Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Mild to moderate SLE	4	657	Risk Ratio (M‐H, Fixed, 95% CI)	2.16 [1.65, 2.83]
1.2 Severe SLE	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.68, 5.85]
2 Hirsutism Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Mild to moderate SLE	4		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Severe SLE	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Menstrual change Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Mild to moderate SLE	3	276	Risk Ratio (M‐H, Fixed, 95% CI)	1.2 [0.38, 3.77]
3.2 Severe SLE	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	2.67 [0.98, 7.22]

Comparison 3. Adverse events

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Referencias

Referencias de los estudios incluidos en esta revisión

Chang 2002 {published data only}

Hartkamp 2004 {published data only}

Nordmark 2005 {published data only}

Petri 2002 {published data only}

Petri 2004 {published data only}

Van Vollenhoven 1995 {published data only}

Van Vollenhoven 1999 {published data only}

Referencias de los estudios excluidos de esta revisión

Barry 1998 {published data only}

Chang 2004 {published data only}

van Vollenhoven 1992 {published data only}

van Vollenhoven 1993 {published data only}

van Vollenhoven 1994 {published data only}

van Vollenhoven 1996 {published data only}

van Vollenhoven 2001 {published data only}

vanVollenhoven 1994b {published data only}

Referencias adicionales

Boumpas 1992

Caccavo 1997

Cates 2003

CDER 2005

CHSG 1991

Derksen 1998

FitzGerald 1999

Genelabs 2001

Hart 1983

Higgins 2006

Homik 2004

Jadad 1996

Johnson 1995

Johnson 1996

Khan 2000

Kingdon 2001

Lee 1993

McCarty 1995

Mok 2003

Nived 1997

Petri 2005

Ruiz‐Irastorza 2001

Schulz 1995

Silman 1997

Singh 1999

Strand 1999

Strand 1999b

Strand 2004

Tugwell 2004

Whelton 2000

Wollaston 2004

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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Instituciones a las que se accedió previamente

Usuarios institucionales

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