title: Placebo response in two long-term randomized psoriasis studies that were negative for rosiglitazone.
abstract: BACKGROUND
  Previous research has suggested that the thiazolidinedione rosiglitazone may possess anti-psoriatic activity.
  
  
  OBJECTIVE
  To compare the efficacy and safety of rosiglitazone with that of placebo in the treatment of chronic plaque psoriasis.
  
  
  METHODS
  Two large-scale, randomized, double-blind, multicenter studies (study A, n = 1563; study B, n = 1032) were conducted over 52 weeks (plus optional 44 weeks safety extension) in an outpatient setting. The subjects (aged 18-75 years) had moderate-to-severe chronic plaque psoriasis affecting >or=10% body surface area (BSA) with plaques of any elevation above normal-appearing skin (or >or=6% BSA involvement with marked elevation) and had not used phototherapy during the previous month or thiazolidinediones within the previous 3 months. Rosiglitazone was administered as 2, 4, or 8 mg tablets once daily. The main outcome measure was the proportion of subjects achieving >or=75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 26.
  
  
  RESULTS
  Rosiglitazone was well tolerated but no more effective than placebo for moderate-to-severe chronic plaque psoriasis. However, there was a large placebo response unrelated to concomitant rescue medication. Interestingly, subjects had been advised to expect a long period before onset of action. At week 26 and across both studies for subjects receiving placebo, the PASI 75 was 9% (48/506) and the PASI 50 (proportion of subjects who achieved at least 50% improvement from baseline) was 27% (135/506). In addition, few subjects withdrew from placebo or rosiglitazone treatment because of 'lack of efficacy' and the majority persisted in the year-long study.
  
  
  CONCLUSIONS
  While these large-scale, robust studies demonstrated that rosiglitazone is not active in psoriasis, they also showed that for a large proportion of subjects receiving placebo, the expectation of a successful treatment, the favorable adverse effect profile of the drug, and the supportive environment of a clinical study conferred beneficial effects. These results may have implications for the design of future placebo-controlled studies in patients with psoriasis.
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Ellis
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Barker
authors.forename: Ann E
authors.initials: AE
authors.lastname: Haig
authors.forename: Christine A
authors.initials: CA
authors.lastname: Parker
authors.forename: Susan
authors.initials: S
authors.lastname: Daly
authors.forename: Deepthi A
authors.initials: DA
authors.lastname: Jayawardene
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D011565:Psoriasis / Q000188:drug therapy*; D000077154:Rosiglitazone; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D003879:Dermatologic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein