Raj Sengupta received grants, honoraria, and expenses for attendance at advisory board meetings or conferences and for giving lectures from AbbVie, Celgene Corporation, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. 2, and 3, followed by every 4 weeks (q4w) starting at Week 4 until Week 48 [Figure ?[Figure1].1]. Starting at Week 16, all patients received open-label secukinumab 150?mg, including all placebo patients (hereafter referred to as placebo-switchers). The end of treatment visit occurred at Week 52 and a post-treatment follow-up visit occurred 12 weeks after the last dose (for all patients regardless of whether they completed the study or discontinued prematurely). After all patients completed Week 16, a primary endpoint analysis was conducted. Although unblinding occurred at the Week 16 analysis, all patients, investigators, and site staff remained blinded throughout the study to the treatment group assigned at randomization (secukinumab 150?mg or placebo). The study was planned to enroll no more than 30% TNFi-IR patients. Data were collected in accordance with Good Clinical Practice guidelines by the study investigators and were analyzed by the sponsor. Data presented here, from the primary analysis at Week 16 to the end-of-study analysis at Week 52 (1-year), were collected from October 18, 2016 (first patient first visit) to March 19, 2019 (last patient last visit). Efficacy outcomes Primary objective The primary objective was to demonstrate that the efficacy of s.c. secukinumab 150?mg is superior to placebo based on the proportion of patients achieving an Assessments of SpondyloArthritis international Society (ASAS) 20 response at Week 16. ASAS20 is defined as a relative improvement of 20% and an absolute improvement of 1 1 unit (on a 10-unit scale) in at least JNJ-64619178 three out of four main ASAS domains (patient global assessment of disease activity, back pain, physical function, and inflammation), with no worsening of 20% and 1 unit (on a 10-unit scale) in the remaining domain. Secondary objectives The secondary objective was to demonstrate that the efficacy of s.c. secukinumab 150?mg is superior to placebo for the following parameters at Week 16: (1) the proportion of patients achieving an ASAS40 response (improvement of 40% and absolute improvement of 2 units [on a 10-unit scale] in Rabbit Polyclonal to Gastrin at least three of the JNJ-64619178 four main ASAS domains, with no worsening at all in the remaining domain); (2) change from baseline of high-sensitivity C-reactive protein (hsCRP); (3) ASAS5/6 response (20% improvement in five of the six ASAS response domains, defines as the four main ASAS domains, along with hsCRP, and lateral spinal mobility); (4) change from baseline in total BASDAI (questions on a JNJ-64619178 0 to 10 scale captured JNJ-64619178 as a continuous VAS, pertaining to the five major symptoms of AS: fatigue, spinal pain, joint pain/swelling, areas of localized tenderness [enthesitis or inflammation of tendons and ligaments], and morning stiffness duration and severity); (5) change from baseline in the Short Form 36 Physical Component Summary (scores range from 0 [maximum disability] to 100 [no disability] for individual domains, with a normative composite summary score of 50); (6) change from baseline in Ankylosing Spondylitis Quality of Life (scores range from 0 [best quality] to 18 [poorest quality]) scores; and (7) ASAS partial remission (a score of 2 units in each of the four core ASAS domains).[23C26] The overall safety and tolerability of secukinumab placebo up to Week JNJ-64619178 16 was assessed by adverse events (AEs), serious AEs (SAEs), laboratory assessments, and vital signs. Safety data during the entire treatment period are presented for the Any secukinumab 150 mg group, which included all patients who received a dose of secukinumab (ie, those originally randomized to secukinumab 150?mg as well as placebo-switchers after receiving their first dose of secukinumab 150 mg). Exploratory objectives The exploratory objective was to assess the primary and secondary endpoints at time points other than.