American Journal of Clinical Dermatology

, Volume 8, Issue 2, pp 93–102 | Cite as

Placebo Response in Two Long-Term Randomized Psoriasis Studies that were Negative for Rosiglitazone

  • Charles N. Ellis
  • Jonathan N. Barker
  • Ann E. Haig
  • Christine A. Parker
  • Susan Daly
  • Deepthi A. Jayawardene
Original Research Article American journal of Clinical Dermatology


Background:Previous research has suggested that the thiazolidinedione rosiglitazone may possess antipsoriatic 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 ≥10% body surface area (BSA) with plaques of any elevation above normal-appearing skin (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 8mg tablets once daily. The main outcome measure was the proportion of subjects achieving ≥75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 26. 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.

Conclusion: 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.


Psoriasis Rosiglitazone Placebo Response Dermatology Life Quality Index Efalizumab 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank the many physicians involved in the Avandia™ Psoriasis Study Group (see below) for their support and efforts in conducting these studies. In addition we would like to thank Jeff Wilkins, Beth Ann Mooney, Carolyn Rainville, and Max Cherny for their invaluable assistance.

The authors provide the following disclosures. Dr Ellis is a consultant to GlaxoSmithKline (GSK) and within the past 5 years has served as a consultant and spoken for various manufacturers of therapies for psoriasis. Dr Ellis also holds rights to the Lattice System Physician’s Global Assessment method for assessing psoriasis severity. Dr Barker is a consultant to GSK and has conducted clinical trials sponsored by GSK. Within the past 5 years he has served as a consultant to, and spoken at symposia sponsored by, various manufacturers of therapies for psoriasis. Mrs Haig, Ms Jayawardene, and Dr Parker are full-time employees of GSK and Dr Daly works on contract for GSK.

Dr Ellis had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The trials are registered on the GSK website under the clinical trials register

Physicians who participated in the Avandia™ Psoriasis Study were:

Study A (no. of centers = 147). USA: Caro, Ivor; Digiovanna, John J.; Farber, Harold F.; Frankel, Ellen H.; Geary, Brian D.; Hassman, David; Kivitz, Alan J.; Sheehan, Mary P.; Sobell, Jeffrey M.; Webster, Guy F.; Edwards, Irene E.; Feldman, Steven R.; Finn, Albert F.; Grande, Kimberly; Horowitz, David; Humeniuk, John M.; Jackson, Jeffrey B.; Kattine, Albert; Kurita, George; Liu, Debra; Rist, Toivo E.; Rostan, Elizabeth F.; Aton, J.K.; Barba, Alicia; Cooksey, David; Corn, Lydia; Duvic, Madeliene; Funicella, Toni; Gilderman, Larry I.; Hamilton, Tiffani; Harvey, David; Heuer, Marvin A.; Jain, Adesh; Jones, Terry; Kaminester, Lewis H.; Lee, Mark; Lee, Patricia; Millikan, Larry; Nunez, Margarita; Rosen, Theodore; Silvers, David R.; Taylor, J. Richard; Baker, Diane; Beutner, Karl A.; Clark, Scott; Conant, Marcus A.; Dunlap, Frank E.; Kimball, Alexa A.; Ko, William; Koo, John; Korman, Neil; Lamerson, Cindy; Matheson, Robert T.; Rich, Phoebe; Swinehart, James M.; Tavelii, Bert G.; Tschen, Eduardo H.; Yamauchi, Paul S.; Breneman, Debra; Bridges, Alina G.; Busbey, Shail; Cunningham, Edwin J.; Decastro, Fernando; Fowler, Joseph; Knutson, Dennis D.; Leonardi, Craig; Lucky, Anne; Mcdonnell, Jonelle; Murakawa, George; Nayak, Anjuli; Russell, Thomas J.; Stein, Linda; Stewart, Daniel M.; Tharp, Michael; Canada: Adams, Stewart; Benohanian, Antranik; Bissonnette, Robert; Carey, Wayne; Gulliver, Wayne; Gupta, Aditya K.; Langley, Richard; Lasko, Benjamin; Murphy, Frank; Murray, Eileen; Poulin, Yves; Rosoph, Les; Shear, Neil; Thomas, Richard; Austria and Germany: Gerlach, Beatrice; Golsch, Stefan; Gschnait, Fritz; Honigsmann, Herbert; Kloevekorn, Winfried; Meyer, Karl G.; Pres, Henrik; Sebastian, Michael; Teichmann, Jorg; Weiss, Karin; Werfel, T.; The Netherlands, Norway, and Belgium: Christensen, Ole; Dahle, John, S; De Cuyper, Christa; De Weert, Jozef; Dela Brassinne, Michel; Delescluse, J; Dikland, W.J.; Heenen, Michel; Heide, R.; Hoop De, Dick; van de Kerkhof, P.C.M.; Koopman, Roland; Lambert, Julien; Moseng, Dagfinn; Prens, E.P.; Prevoo, Ruud; Ree, Kristian; Roelandts, Rik; Roseeuw, Diane; Rustenberg, Berit; Steinkjer, Bjarte; Thio, Bing; France, Italy, and Spain: Cambazard, Frederic M.; Castells, Antoni; Chimenti, Sergio; Drouault, Yorik M.; Dubertret, Louis M.; Ferrandiz, Carlos; Fonseca, Eduardo; Herrero Mateu, Carmen; Lopez Estebaranz, Jose L.; Moreno, Jose Carlos; Ortonne, Jean-Paul M.; Puddu, Pierto; Pujol, Ramon; UK and Australia: Berth-Jones, John; Douglas, William S.; Foley, Peter; Friedmann, Peter S.; Griffiths, Christopher E.M.; Murrell, Dedee; Omerod, Anthony D.; Ratnavel, Ravi C.; Sinclair, Rodney; Weightman, Warren.

Study B (no. of centers = 92). USA: Anderson, Bryan; Balin, Arthur K.; Ehrlich, Alison; Greenstein, David; Kauffman, Lisa; Konnikov, Nellie; Krusinski, Paul; Levin, Nikki; Mangione, Antoniette; Nadel, Ronald; Parish, Lawrence C.; Phillips, Tama; Van Voorhees, Abby; Vujevich, Marion M.; Broker, Robert; Clemons, Donald E.; Donahue, Michael; Kaplan, Robert J.; Loven, Keith; Mikell, Oswald L.; Murray, John C.; Nasir, Adnan; Nurnberg, Ruth; Strout, Cynthia; Cole, Frank N.; Davis, Stephen A.; Gaughf, Claudia N.; Herzog, Jo Lynne; Kaye, William A.; Ling, Mark; Massengale, William T.; Miller, Richard; Morris, Amy M.; Nelson, Christopher; Noveck, Robert; Pandya, Amit G.; Salazar, Gilbert; Stieglitz, Sam; Weiss, Jonathan S.; Yates, Ruth A.; Baskin, Morissa; Drehobl, Margaret; Fitzpatrick, Richard; Forsha, Douglas; Henderson, C. Dan; Henry, Dan C.; Johnston, Kathryn; Larson, Wayne; Limova, Marketa; Maloney, J. Michael; Mollen, Martin D.; Moy, Lawrence; Portnoy, Edward; Sawada, Kathleen Y.; Shapiro, William M.; Shewmake, Stephen; Simpson, Karen; Spector, Sheldon L.; Werschler, W. Philip; Wong, Darryl; Basler, Rodney; Belsito, Donald; Crosby, David; Farrell, James; Fenyk, John; Glinert, Robert; Gonzalez, Michael; Heffernan, Michael; Herszenson, Sidney; Huerter, Christopher; Kirsner, Robert; Kozeny, Keith; Kreuger, Gerald G.; Mark, George; Monroe, Eugene; Moore, Jeffrey K.; Muccini, Joseph A.; Schlessinger, Joel; Solomon, Noguera; Vaughn, Douglas; Ward, Diane; Canada: Bernstein, Steven; Bourcier, Marc; Carruthers, Alastair; Gratton, David; Guenther, Lyn; Landells, Ian; Loranger, Louise; Lynde, Charles W.; Papp, Kim; Sapijaszko, Mariusz; Sapra, Sheetal; Sibbald, Ronald G.


  1. 1.
    Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy 2004; 3: 121–8PubMedCrossRefGoogle Scholar
  2. 2.
    Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004; 113: 1664–75PubMedGoogle Scholar
  3. 3.
    Feldman SR, Evans C, Russell MW. Systemic treatment for moderate to severe psoriasis: estimates of failure rates and direct medical costs in a north-eastern US managed care plan. Dermatol Treat 2005; 16: 37–42CrossRefGoogle Scholar
  4. 4.
    Pershadsingh HA, Sproul JA, Benjamin E. Treatment of psoriasis with troglitazone therapy. Arch Dermatol 1998; 134: 1304–5PubMedCrossRefGoogle Scholar
  5. 5.
    Ellis CN, Varani J, Fisher GJ. Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation. Arch Dermatol 2000; 136: 609–16PubMedCrossRefGoogle Scholar
  6. 6.
    Robertshaw H, Friedmann PS. Pioglitazone: a promising therapy for psoriasis. Br J Dermatol 2005; 152: 189–91PubMedCrossRefGoogle Scholar
  7. 7.
    Shafiq N, Malhotra S, Pandhi P. Pilot trial: pioglitazone versus placebo in patients with plaque psoriasis (the P6). Int J Dermatol 2005; 44: 328–33PubMedCrossRefGoogle Scholar
  8. 8.
    Mohanty P, Aljada A, Ghanim H. Evidence for a potent anti-inflammatory effect of rosiglitazone. Clin Endocrinol Metab 2004; 89: 2728–35CrossRefGoogle Scholar
  9. 9.
    Venkatraman MS, Chittiboyina A, Meingassner J. Alpha-lipoic acid-based PPARgamma agonists for treating inflammatory skin diseases. Arch Dermatol Res 2004; 296: 97–104PubMedCrossRefGoogle Scholar
  10. 10.
    Bhagavathula N, Nerusu KC, Lal A. Rosiglitazone inhibits proliferation, motility, and matrix metalloproteinase production in keratinocytes. J Invest Dermatol 2004; 122: 130–9PubMedCrossRefGoogle Scholar
  11. 11.
    GlaxoSmithKline. Clinical trial register (292) document number CM2003/00018/00 study ID BRL-049653/292: a randomized, double-blind, placebo-controlled trial to assess three dose levels of rosiglitazone maleate (rosiglitazone) in the treatment of moderate to severe plaque psoriasis [online]. Available from URL: [Accessed 2006 Apr 7]
  12. 12.
    Langley RGB, Ellis CN. Evaluating psoriasis with Psoriasis Area and Severity Index (PASI), Psoriasis Global Assessment (PGA), and Lattice System Physician’s Global Assessment (LS-PGA). J Am Acad Dermatol 2004; 51: 563–9PubMedCrossRefGoogle Scholar
  13. 13.
    Chodorowska G, Wojnowska D, Juszkiewicz-Borowiec M. C-reactive protein and alpha2-macroglobulin plasma activity in medium-severe and severe psoriasis. J Eur Acad Dermatol Venereol 2004; 18: 180–3PubMedCrossRefGoogle Scholar
  14. 14.
    Rocha-Pereira P, Santos-Silva A, Rebelo I. The inflammatory response in mild and in severe psoriasis. Br J Dermatol 2004; 150: 917–28PubMedCrossRefGoogle Scholar
  15. 15.
    Carlin CS, Feldman SR, Krueger JG. A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endpoint in the assessment of psoriasis. J Am Acad Dermatol 2004; 50: 859–66PubMedCrossRefGoogle Scholar
  16. 16.
    Krueger GG, Papp KA, Stough DB. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol 2002; 47: 821–33PubMedCrossRefGoogle Scholar
  17. 17.
    Gottlieb AB, Matheson RT, Lowe N. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol 2003; 139: 1627–32PubMedCrossRefGoogle Scholar
  18. 18.
    Reich K, Nestle FO, Papp K. Infliximab induction and maintenance therapy for moderate to severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366: 1367–74PubMedCrossRefGoogle Scholar
  19. 19.
    Schön MP. Advances in psoriasis treatment. Lancet 2005; 366: 1333–5PubMedCrossRefGoogle Scholar
  20. 20.
    Krueger G, Koo J, Lebwohl M.The impact of psoriasis on quality of life.Arch Dermatol2001;137:280–4PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Charles N. Ellis
    • 1
  • Jonathan N. Barker
    • 2
  • Ann E. Haig
    • 3
  • Christine A. Parker
    • 4
  • Susan Daly
    • 4
  • Deepthi A. Jayawardene
    • 3
  1. 1.Department of DermatologyUniversity of Michigan Medical SchoolAnn ArborUSA
  2. 2.St John’s Institute of DermatologySt Thomas’ HospitalLondonUK
  3. 3.Medicine Development Centre, GlaxoSmithKlinePhiladelphiaUSA
  4. 4.Medicine Development Centre, GlaxoSmithKlineGreenfordUK

Personalised recommendations