RT Journal Article SR Electronic T1 Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 495 OP 503 DO 10.3899/jrheum.150117 VO 43 IS 3 A1 Witold Tlustochowicz A1 Proton Rahman A1 Bruno Seriolo A1 Gerhard Krammer A1 Brian Porter A1 Albert Widmer A1 Hanno B. Richards YR 2016 UL http://www.jrheum.org/content/43/3/495.abstract AB Objective. To evaluate the efficacy and safety of secukinumab, a fully human antiinterleukin-17A monoclonal antibody, administered with an intravenous (IV) or subcutaneous (SC) loading regimen versus placebo, in patients with active rheumatoid arthritis (RA).Methods. In this phase II, double-blind, double-dummy, 52-week study (ClinicalTrials.gov NCT01359943), 221 patients with inadequate response to methotrexate were randomized (2:2:1) to secukinumab, IV loading 10 mg/kg at baseline, Weeks 2 and 4, then SC 150 mg every 4 weeks (n = 88); secukinumab SC loading 150 mg once weekly for 5 weeks, then every 4 weeks (n = 89); or a matching placebo (followed by secukinumab 150 mg every 4 weeks starting Week 16; n = 44). The primary endpoint was superior efficacy of pooled secukinumab versus placebo using American College of Rheumatology 20% response (ACR20) at Week 12.Results. The primary efficacy endpoint was not met: ACR20 response at Week 12 was 49.2% for pooled secukinumab versus 40.9% for placebo (p = 0.3559). These variables improved significantly with pooled secukinumab versus placebo at Week 12 (all p < 0.05): the 28-joint Disease Activity Score (DAS28), patient’s and physician’s global assessment of disease activity, patient’s assessment of RA pain, and high-sensitivity C-reactive protein levels. Results of continuous efficacy outcomes were similar between the IV and SC loading regimens. The most frequent adverse events were infections, with similar rates across secukinumab and placebo.Conclusion. Although the primary endpoint (ACR20) was not met, secukinumab demonstrated improved efficacy in reducing disease activity over placebo as measured by DAS28 and other secondary endpoints.