Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis
Philip J Mease, Iain B McInnes, Bruce Kirkham, Arthur Kavanaugh, Proton Rahman, Désirée van der Heijde, Robert Landewé, Peter Nash, Luminita Pricop, Jiacheng Yuan, Hanno B Richards, Shephard Mpofu, FUTURE 1 Study Group, Francisco Caeiro, Enrique Soriano, Marcos Baravalle, Raul Ceitlin, Oscar Rillo, Judith Carrio, Stephen Hall, Peter Nash, Filip Van den Bosch, Kurt de Vlam, Piet Geusens, Marcelo Pinheiro, Cristiano Zerbini, Mauro Keiserman, Kim Papp, Clode Lessard, Jean-Luc Tremblay, Proton Rahman, Majed Mustafa, J Carter Thorne, Pnina Langevitz, Tatiana Reitblat, Itzhak Rosner, Ori Elkayam, Bruno Frediani, Rosario Foti, Fabrizio Cantini, Silvano Adami, Sandra Navarra, Emmanuel Perez, Allan Lanzon, Rosario Baes, Auxencio Lucero Jr, Carjen Gulay-Carvajal, Julie Li-Yu, Perry Tan, Juan Javier, Rodica Chirieac, Ruxandra Maria Ionescu, Simona Rednic, Evgeny Nasonov, Marina Stanislav, Tatiana Raskina, Olga Ershova, Nadezda Izmozherova, Olga Lesnyak, Evgenii Zotkin, Kam Hon Yoon, Anita Lim, Ying Ying Katy Leung, Paijit Asavatanabodee, Parawee Suwannalai, Ratanavadee Nanagara, Worawit Louthrenoo, Maria Strapkova, Hasan Tahir, Iain Mc Innes, Thomas Sheeran, Philip Helliwell, Bruce Kirkham, Krasimira Shimbova, Rumen Stoilov, Mariyana Mihaylova, Eva Dokoupilova, Petr Vitek, Dagmar Galatikova, Izabella Janecka, Jerzy Supronik, Joachim Sieper, Reiner Kurthen, Georg Dahmen, Winfried Demary, Hubert Nuesslein, Elizaveta Degtyareva, Olga Maus, Joern Kekow, Andrea Rubbert-Roth, Juergen Rech, Florian Schuch, Siegfried Wassenberg, Rene Martz, Wolfgang Spieler, Juergen Braun, Elias Halpert, Elvia Moreta, Jane Box, Clarence Legerton 3rd, Kathleen Flint, John Starr, Ramina Jajoo, Paul Caldron, John Tesser, Ellen Frankel, Hisham El-Kadi, Dianne Petrone, Andreas Reimold, Atul Singhal, Prashanth Sunkureddi, Frank Wellborne, John Budd, Christine Codding, Michael Kohen, Alan Kivitz, Vishala Chindalore, Philip Mease, Jacob Aelion, Eric Lee, Robert Valente, Alice Gottlieb, Philip J Mease, Iain B McInnes, Bruce Kirkham, Arthur Kavanaugh, Proton Rahman, Désirée van der Heijde, Robert Landewé, Peter Nash, Luminita Pricop, Jiacheng Yuan, Hanno B Richards, Shephard Mpofu, FUTURE 1 Study Group, Francisco Caeiro, Enrique Soriano, Marcos Baravalle, Raul Ceitlin, Oscar Rillo, Judith Carrio, Stephen Hall, Peter Nash, Filip Van den Bosch, Kurt de Vlam, Piet Geusens, Marcelo Pinheiro, Cristiano Zerbini, Mauro Keiserman, Kim Papp, Clode Lessard, Jean-Luc Tremblay, Proton Rahman, Majed Mustafa, J Carter Thorne, Pnina Langevitz, Tatiana Reitblat, Itzhak Rosner, Ori Elkayam, Bruno Frediani, Rosario Foti, Fabrizio Cantini, Silvano Adami, Sandra Navarra, Emmanuel Perez, Allan Lanzon, Rosario Baes, Auxencio Lucero Jr, Carjen Gulay-Carvajal, Julie Li-Yu, Perry Tan, Juan Javier, Rodica Chirieac, Ruxandra Maria Ionescu, Simona Rednic, Evgeny Nasonov, Marina Stanislav, Tatiana Raskina, Olga Ershova, Nadezda Izmozherova, Olga Lesnyak, Evgenii Zotkin, Kam Hon Yoon, Anita Lim, Ying Ying Katy Leung, Paijit Asavatanabodee, Parawee Suwannalai, Ratanavadee Nanagara, Worawit Louthrenoo, Maria Strapkova, Hasan Tahir, Iain Mc Innes, Thomas Sheeran, Philip Helliwell, Bruce Kirkham, Krasimira Shimbova, Rumen Stoilov, Mariyana Mihaylova, Eva Dokoupilova, Petr Vitek, Dagmar Galatikova, Izabella Janecka, Jerzy Supronik, Joachim Sieper, Reiner Kurthen, Georg Dahmen, Winfried Demary, Hubert Nuesslein, Elizaveta Degtyareva, Olga Maus, Joern Kekow, Andrea Rubbert-Roth, Juergen Rech, Florian Schuch, Siegfried Wassenberg, Rene Martz, Wolfgang Spieler, Juergen Braun, Elias Halpert, Elvia Moreta, Jane Box, Clarence Legerton 3rd, Kathleen Flint, John Starr, Ramina Jajoo, Paul Caldron, John Tesser, Ellen Frankel, Hisham El-Kadi, Dianne Petrone, Andreas Reimold, Atul Singhal, Prashanth Sunkureddi, Frank Wellborne, John Budd, Christine Codding, Michael Kohen, Alan Kivitz, Vishala Chindalore, Philip Mease, Jacob Aelion, Eric Lee, Robert Valente, Alice Gottlieb
Abstract
Background: In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in such patients.
Methods: In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains.
Results: ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group.
Conclusions: Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.).
Source: PubMed