Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis
Dominique Baeten, Joachim Sieper, Jürgen Braun, Xenofon Baraliakos, Maxime Dougados, Paul Emery, Atul Deodhar, Brian Porter, Ruvie Martin, Mats Andersson, Shephard Mpofu, Hanno B Richards, MEASURE 1 Study Group, MEASURE 2 Study Group, Filip Van den Bosch, Adrien Nzeusseu, Kurt de Vlam, Piet Geusens, Boycho Oparanov, Rasho Rashkov, Anastas Batalov, Ivan Goranov, Ivan Kazmin, Tim McCarthy, Robert Inman, Proton Rahman, Thierry Schaeverbeke, Minh N'Guyen, Philippe Bertin, Bruno Frediani, Silvano Adami, Rosario Foti, Giovanni Triolo, Enrico Fusaro, Franco Franceschini, Beatriz Zazueta, Marco Maradiaga, Hilario Avila, Mario Garza, Dominique Baeten, Hans Bijlsma, Alfredo Berrocal, Boris Garro, Rocio Gamboa, Oswaldo Castaneda, Felipe Becerra, Marina Stanislav, Tatyana Salnikova, Alexey Maslyanskiy, Olga Ershova, Nadezda Izmozherova, Olga Lesniak, Jui-Cheng Tseng, Cheng-Chung Wei, Huri Ozdogan, Bunyamin Kisacik, Fatos Onen, Hasan Tahir, Andrew Ostor, Nick Barkham, Lesley Kay, Juergen Braun, Georg Dahmen, Andrea Rubbert-Roth, Siegfried Wassenberg, Peter Oelzner, Hubert Nuesslein, Ruediger Moericke, Juergen Rech, Joachim Sieper, Atul Deodhar, Alan Kivitz, Jacob Aelion, Michael Kohen, William Knibbe, Sean LaSalle, Song Zang, Stanley Cohen, Michael Brooks, Winfried Graninger, Rieger Jorg, Omid Zamani, Louis Bessette, Martin Cohen, Tim McCarthy, Andre Beaulieu, Karel Pavelka, Dagmar Galatikova, Eva Dokoupilova, Marjatta Leirisalo-Repo, Leena Paimela, Pentti Järvinen, Tuulikki Sokka-Isler, Esa Rouhe, Seinäjoen keskussairaala, Rosario Foti, Raffaele Pellerito, Silvano Adami, Dominique Baeten, Johannes Bijlsma, Vasiliy Trofimov, Nadezda Izmozherova, Natalia Vezikova, Eugeny Zotkin, Marina Stanislav, Olga Ershova, Nino Mosesova, Lui Nai Lee, Peter Cheung, Alejandro Balsa, Ricardo Blanco, Francisco J Blanco, Carlos Gonzalez, Bettina Bannert, Benz Daniela, Jean Dudler, Adrian Ciurea, Hasan Tahir, Helena Marzo-Ortega, Karl Gaffney, Kirsten Mackay, Christine Codding, Walter Dorman, Clarence Legerton 3rd, Alan Kivitz, Mohamed Khan, Eric Lee, Paul Caldron, J Frederick Wolfe, Areena Swarup, Atul Singhal, Juergen Braun, Joachim Sieper, Hans-Peter Tony, Dominique Baeten, Joachim Sieper, Jürgen Braun, Xenofon Baraliakos, Maxime Dougados, Paul Emery, Atul Deodhar, Brian Porter, Ruvie Martin, Mats Andersson, Shephard Mpofu, Hanno B Richards, MEASURE 1 Study Group, MEASURE 2 Study Group, Filip Van den Bosch, Adrien Nzeusseu, Kurt de Vlam, Piet Geusens, Boycho Oparanov, Rasho Rashkov, Anastas Batalov, Ivan Goranov, Ivan Kazmin, Tim McCarthy, Robert Inman, Proton Rahman, Thierry Schaeverbeke, Minh N'Guyen, Philippe Bertin, Bruno Frediani, Silvano Adami, Rosario Foti, Giovanni Triolo, Enrico Fusaro, Franco Franceschini, Beatriz Zazueta, Marco Maradiaga, Hilario Avila, Mario Garza, Dominique Baeten, Hans Bijlsma, Alfredo Berrocal, Boris Garro, Rocio Gamboa, Oswaldo Castaneda, Felipe Becerra, Marina Stanislav, Tatyana Salnikova, Alexey Maslyanskiy, Olga Ershova, Nadezda Izmozherova, Olga Lesniak, Jui-Cheng Tseng, Cheng-Chung Wei, Huri Ozdogan, Bunyamin Kisacik, Fatos Onen, Hasan Tahir, Andrew Ostor, Nick Barkham, Lesley Kay, Juergen Braun, Georg Dahmen, Andrea Rubbert-Roth, Siegfried Wassenberg, Peter Oelzner, Hubert Nuesslein, Ruediger Moericke, Juergen Rech, Joachim Sieper, Atul Deodhar, Alan Kivitz, Jacob Aelion, Michael Kohen, William Knibbe, Sean LaSalle, Song Zang, Stanley Cohen, Michael Brooks, Winfried Graninger, Rieger Jorg, Omid Zamani, Louis Bessette, Martin Cohen, Tim McCarthy, Andre Beaulieu, Karel Pavelka, Dagmar Galatikova, Eva Dokoupilova, Marjatta Leirisalo-Repo, Leena Paimela, Pentti Järvinen, Tuulikki Sokka-Isler, Esa Rouhe, Seinäjoen keskussairaala, Rosario Foti, Raffaele Pellerito, Silvano Adami, Dominique Baeten, Johannes Bijlsma, Vasiliy Trofimov, Nadezda Izmozherova, Natalia Vezikova, Eugeny Zotkin, Marina Stanislav, Olga Ershova, Nino Mosesova, Lui Nai Lee, Peter Cheung, Alejandro Balsa, Ricardo Blanco, Francisco J Blanco, Carlos Gonzalez, Bettina Bannert, Benz Daniela, Jean Dudler, Adrian Ciurea, Hasan Tahir, Helena Marzo-Ortega, Karl Gaffney, Kirsten Mackay, Christine Codding, Walter Dorman, Clarence Legerton 3rd, Alan Kivitz, Mohamed Khan, Eric Lee, Paul Caldron, J Frederick Wolfe, Areena Swarup, Atul Singhal, Juergen Braun, Joachim Sieper, Hans-Peter Tony
Abstract
Background: Secukinumab is an anti-interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis.
Methods: In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16.
Results: In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn's disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.
Conclusions: Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.).
Source: PubMed