Placebo Response in Two Long-Term Randomized Psoriasis Studies that were Negative for Rosiglitazone
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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.
KeywordsPsoriasis Rosiglitazone Placebo Response Dermatology Life Quality Index Efalizumab
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 registerhttp://ctr.gsk.co.uk/
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.
- 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: http://ctr.gsk.co.uk/Summary/rosiglitazone/studylist.asp [Accessed 2006 Apr 7]