Efficacy and Safety of Secukinumab 150 mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-week Results from MEASURE 4 Study

Abstract

Introduction: To evaluate the efficacy and safety of secukinumab 150 mg, with or without a loading regimen, using a self-administered prefilled syringe in patients with ankylosing spondylitis (AS) over 104 weeks from the MEASURE 4 study.

Methods: Patients (N = 350) with active AS were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with loading dose (150 mg), without loading dose (150 mg no load), or placebo. All patients received secukinumab or placebo at baseline, weeks 1, 2, and 3 and every 4 weeks starting at week 4. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) at week 16.

Results: A total of 96.9% of patients (339/350) completed 16 weeks and 82.6% (289/350) completed 104 weeks of treatment. The ASAS20 response rate at week 16 was 59.5% and 61.5% with 150 and 150 mg no load groups, respectively, versus placebo (47%; P = 0.057 and 0.054, respectively); the primary endpoint was not met. Increases in response rates achieved with secukinumab for ASAS20 at week 16 were sustained through week 104. The safety profile of secukinumab 150 mg, with or without a loading regimen, showed no new or unexpected safety signals.

Conclusions: Secukinumab 150 mg, with or without loading regimen, provided rapid and sustained decreases in the signs and symptoms of patients with AS, but the differences were not statistically significant at week 16 due to higher than expected placebo responses. The responses and safety profile were consistent with previous phase 3 studies and sustained through 2 years.

Trial registration: ClinicalTrials.gov identifier, NCT02159053.

Funding: Novartis Pharma AG, Basel, Switzerland.

Keywords: Ankylosing spondylitis; Biologics; IL-17A; Secukinumab.

Figures

Fig. 1

Patient disposition through week 104. The secukinumab groups received either s.c. secukinumab 150 mg loading dose weekly followed by a maintenance dose q4w starting at week 4 or s.c. secukinumab 150 mg without loading dose at baseline (with placebo doses at weeks 1, 2, and 3), followed by q4w dosing starting at week 4. Placebo was given on the same dosing schedule as the loading regimen, and all placebo patients were switched to s.c. secukinumab 150 mg q4w at week 16 in an open-label fashion. q4w, every 4 weeks; s.c., subcutaneous

Fig. 2

ASAS20 (a) and ASAS40 (b) response rates through week 16 (placebo-controlled phase). Shown are the proportions of patients with an ASAS20 response (a improvement of ≥ 20% and absolute improvement of ≥ 1 unit [on a 10-unit scale] in at least three of the four main ASAS domains, with no worsening by ≥ 20% in the remaining domain) and the proportion with ASAS40 responses (b improvement of ≥ 40% and absolute improvement of ≥ 2 units [on a 10-unit scale] in at least three of the four main ASAS domains, with no worsening in the remaining domain). *P < 0.0001; §P < 0.01; ‡P < 0.05 versus placebo (P values at week 16 were adjusted for multiplicity of testing); missing data were imputed as non-response through week 16. ASAS Assessment of SpondyloArthritis International Society, N number of patients randomized