Papp 2012a

Methods	RCT, placebo‐controlled, double blind Date of study: July 2008‐August 2009 Location: 42 centres in USA, Canada
Participants	Randomised: 197 participants (tofacitinib 2 mg (49) mean age 46 years, 29 male; tofacitinib 5 (49) mean age 44 years, 29 male; tofacitinib 15 (49) mean age 44 years, 31 male; placebo (n = 50) mean age 44 years, 36 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 13, BSA ≥ 15%), age ≥ 18 Number of allowed previous biologic treatments: any Exclusion criteria Had an active infection Had past history of malignant tumour (with the exception of adequately treated or excised basal cell or squamous cell carcinoma, or cervical carcinoma in situ) Dropouts and withdrawals 48/197 (24%); Tofacitinib 2 mg (11): AE (1), lack efficiency (2), lost to follow‐up (4), decision (3), other (1) Tofacitinib 5 mg (11): AE (2), lack efficiency (3), lost to follow‐up (2), decision (4) Tofacitinib 15 mg (6): AE (3), lack efficiency (1), other (1), decision (1) Placebo (20): AE (3), lack efficiency (9), lost to follow‐up (1), decision (7)
Interventions	Intervention A. Tofacitinib (n = 49), orally, 2 mg, twice a day, 12 weeks Control intervention B. Tofacitinib, (n = 49), orally, 5 mg, twice a day, 12 weeks C. Tofacitinib (n = 49), orally, 15 mg, twice a day, 12 weeks D. Placebo (n = 50), orally, twice a day, 12 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial Safety Proportion of participants achieving a PASI 50 response (weeks 2, 4, 8, 12, 14 and 16) Proportion of participants achieving a PASI 90 response week 12 Actual and change from baseline in PASI and PASI component scores baseline/day 1 and weeks 2, 4, 8, 12, 14 and 16 Proportion of participants with PGA of clear/almost clear, weeks 2, 4, 8, 12, 14 and 16 Proportion of participants achieving a PASI 75 response (weeks 2, 4, 8, 14 and 16)
Notes	Funding source, quote (p 668): "This study was funded by Pfizer Inc" Declarations of interest (appendix): "K.A.P. has been a principal investigator, an advisor or consultant, a Scientific Officer, member of a Scientific Advisory Board and a speaker for the following groups: Abbott, Amgen, Astellas, Celgene, Centocor‐Ortho Biotech, Incyte, Isotechnika, Janssen, Lilly, Medimmune, Merck, Pfizer Inc. and Novartis. A.M. has been on the Advisory Board, been a consultant to, been an investigator for, been a speaker for, obtained a research grant from, or obtained honoraria from the following groups: Abbott, Allergan, Amgen, Astellas, Asubio, Celgene, Centocor, DUSA, Eli Lilly, Galderma, Genentech, Novartis, Novo Nordisk, Pfizer Inc., Promius, Stiefel, Syntrix Biosystems, Warner Chilcott and Wyeth. B.S. has been a principal investigator, an advisor or consultant, or a speaker for the following groups: Abbot, Amgen, Celgene, Centocor‐Ortho Biotech, Janssen, Pfizer Inc., Maruho and Novartis. R.G.L. has been an investigator, served as a principal investigator or on the Advisory Board, or been a speaker for the following groups: Abbott, Amgen, Centocor⁄Ortho Biotech, Pfizer Inc., Novartis and Celgene. R.W., S.K., H.T., P.G. and M.B. are employees of Pfizer Inc. J.A.H. was a full‐time employee of Pfizer Inc. during the conduct and reporting of the study and now works at Novartis Pharma AG, Basel, Switzerland. "
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 669): "A computer‐generated central randomisation schema was implemented in an automated web ⁄telephone system." Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (p 669): "A computer‐generated central randomisation schema was implemented in an automatedTreatment identification was concealed by use of study drugs that were identical in labelling, packaging, appearance and odour" web ⁄telephone system." Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 669): "Patients, investigational site staff, the Pfizer study team and data analysts were blinded to treatment from the time of randomisation until database lock... Treatment identification was concealed by use of study drugs that were identical in labelling, packaging, appearance and odour" Comment: probably one
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 669): "Patients, investigational site staff, the Pfizer study team and data analysts were blinded to treatment from the time of randomisation until database lock... Treatment identification was concealed by use of study drugs that were identical in labelling, packaging, appearance and odour" Comment: probably one
Incomplete outcome data (attrition bias) All outcomes	Low risk	197 included / 195 analysed Quote (p 670): "The full analysis set included all randomised patients who received one or more doses of investigational drug...This population ... represents a modified intent‐to‐treat analysis... Patients with missing values had the missing values imputed but last observation carried forward.... As a sensitivity analysis the patients [with missing values] were also considered nonresponders (NRI)" Comment: mITT and two patients out of 197 not analysed
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT00678210). The pre‐specified outcomes and those mentioned in the methods section appeared to have been reported