TY - JOUR
T1 - Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis
AU - Baeten, Dominique
AU - Sieper, Joachim
AU - Braun, Jürgen
AU - Baraliakos, Xenofon
AU - Dougados, Maxime
AU - Emery, Paul
AU - Deodhar, Atul
AU - Porter, Brian
AU - Martin, Ruvie
AU - Andersson, Mats
AU - Mpofu, Shephard
AU - Richards, Hanno B.
AU - AUTHOR GROUP
AU - van den Bosch, Filip
AU - Nzeusseu, Adrien
AU - de Vlam, Kurt
AU - Geusens, Piet
AU - Oparanov, Boycho
AU - Rashkov, Rasho
AU - Batalov, Anastas
AU - Goranov, Ivan
AU - Kazmin, Ivan
AU - McCarthy, Tim
AU - Inman, Robert
AU - Rahman, Proton
AU - Schaeverbeke, Thierry
AU - N'Guyen, Minh
AU - Bertin, Philippe
AU - Frediani, Bruno
AU - Adami, Silvano
AU - Foti, Rosario
AU - Triolo, Giovanni
AU - Fusaro, Enrico
AU - Franceschini, Franco
AU - Zazueta, Beatriz
AU - Maradiaga, Marco
AU - Avila, Hilario
AU - Garza, Mario
AU - Bijlsma, Hans
AU - Berrocal, Alfredo
AU - Garro, Boris
AU - Gamboa, Rocio
AU - Castaneda, Oswaldo
AU - Becerra, Felipe
AU - Stanislav, Marina
AU - Salnikova, Tatyana
AU - Maslyanskiy, Alexey
AU - Ershova, Olga
AU - Izmozherova, Nadezda
AU - Lesniak, Olga
AU - Tseng, Jui-Cheng
PY - 2015
Y1 - 2015
N2 - 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.)
AB - 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.)
U2 - https://doi.org/10.1056/NEJMoa1505066
DO - https://doi.org/10.1056/NEJMoa1505066
M3 - Article
C2 - 26699169
SN - 0028-4793
VL - 373
SP - 2534
EP - 2548
JO - New England journal of medicine
JF - New England journal of medicine
IS - 26
ER -