Dominique Baeten1, Joachim Sieper, Jürgen Braun, Xenofon Baraliakos, Maxime Dougados, Paul Emery, Atul Deodhar, Brian Porter, Ruvie Martin, Mats Andersson, Shephard Mpofu, Hanno B Richards. 1. From the Academic Medical Center, University of Amsterdam, Amsterdam (D.B.); Charité University Medicine Berlin, Berlin (J.S.), and Rheumazentrum Ruhrgebiet, Herne (J.B., X.B.) - both in Germany; Paris Descartes University and Department of Rheumatology, Hôpital Cochin, Paris (M.D.); Leeds Musculoskeletal Biomedical Research Unit, Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom (P.E.); Oregon Health and Science University, Portland (A.D.); Novartis Pharmaceuticals, East Hanover, NJ (B.P., R.M.); and Novartis Pharma, Basel, Switzerland (M.A., S.M., H.B.R.).
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.).
RCT Entities:
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.).
Authors: Katayoon Bidad; Eric Gracey; Kasey S Hemington; Josiane C S Mapplebeck; Karen D Davis; Robert D Inman Journal: Nat Rev Rheumatol Date: 2017-06-15 Impact factor: 20.543
Authors: Edouard Forcade; Katelyn Paz; Ryan Flynn; Brad Griesenauer; Tohti Amet; Wei Li; Liangyi Liu; Giorgos Bakoyannis; Di Jiang; Hong Wei Chu; Mercedes Lobera; Jianfei Yang; David S Wilkes; Jing Du; Kate Gartlan; Geoffrey R Hill; Kelli Pa MacDonald; Eduardo L Espada; Patrick Blanco; Jonathan S Serody; John Koreth; Corey S Cutler; Joseph H Antin; Robert J Soiffer; Jerome Ritz; Sophie Paczesny; Bruce R Blazar Journal: JCI Insight Date: 2017-06-15