Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain and inflammation, and are considered the cornerstone of pharmacological intervention in patients with radiographic axial spondyloarthritis (r-axSpA); however, the long-term use of NSAIDs is debatable due to their restricted therapeutic potential and the risk of side effects and complications. Therefore, reduction in NSAID intake is desirable in r-axSpA patients. Here, we report the long-term NSAID-sparing effect of secukinumab over 4 years in patients with r-axSpA. This post hoc analysis pooled data from 3 secukinumab trials (MEASURE 2-4) for each secukinumab maintenance dose of 150 and 300 mg, regardless of the loading dose regimen being i.v. or s.c. NSAID intake was evaluated prospectively using the Assessment of SpondyloArthritis International Society (ASAS)-NSAID score. Patients with an ASAS-NSAID score > 0 at baseline were analysed. NSAID-sparing endpoints included the mean change in the ASAS-NSAID score, the proportion of patients achieving 50% reduction, and the proportion of patients with an ASAS-NSAID score < 10. Percentages of patients who achieved BASDAI ≤ 2 were also assessed. Overall, 562 patients were included in this pooled analysis (secukinumab: 150 mg, N = 467; 300 mg, N = 95). The mean ASAS-NSAID score decreased with time in both the secukinumab 150 mg and 300 mg dose groups. The proportion of patients who achieved 50% reduction in the ASAS-NSAID score and clinically meaningful reduction of ASAS-NSAID score < 10 increased with time in both dose groups and in both low and high NSAID intake patients. The percentage of patients with a clinically relevant improvement (BASDAI ≤ 2) was consistently higher in patients with an ASAS-NSAID score < 10 than in patients with an ASAS-NSAID score ≥ 10. Secukinumab provided sustained, long-term NSAID-sparing effects in patients with r-axSpA for up to 4 years of treatment, as measured using the ASAS-NSAID score. Trial registered at clinicaltrials.gov: NCT01649375 ( https://clinicaltrials.gov/ct2/show/NCT01649375 ); NCT02008916 ( https://clinicaltrials.gov/ct2/show/NCT02008916 ); NCT02159053 ( https://clinicaltrials.gov/ct2/show/NCT02159053 ).

Long-term effects of interleukin-17A inhibition with secukinumab in active ankylosing spondylitis: 3-year efficacy and safety results from an extension of the Phase 3 MEASURE 1 trial.

OBJECTIVES: Secukinumab, a fully human anti-IL-17A monoclonal antibody, provided rapid and sustained improvements in signs and symptoms of ankylosing spondylitis (AS) over 2 years in the Phase 3 MEASURE 1 trial. Here, we report efficacy and safety after 3 years of treatment. METHODS: AS subjects completing 2 years of treatment every 4 weeks with subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) entered a separate 3-year extension study (NCT01863732). Assessments included ASAS20/40, ASAS5/6, BASDAI, BASDAI 50, BASFI, BASMI, SF-36 physical component summary, ASAS partial remission and ASDAS-CRP. Results were also analysed by prior anti-TNF treatment status. RESULTS: Among 290 subjects completing the core trial, 274 entered the extension study, with 260 subjects (94.9%) completing 156 weeks of treatment. ASAS20/40 response (observed) was 80.2%/61.6% in the IV→150 mg group and 75.5%/50.0% in the IV→75 mg group after 156 weeks. Sustained improvements were also seen in BASDAI, BASFI, BASMI and across all other endpoints regardless of previous exposure to anti-TNF agents. Mean secukinumab exposure was 964.3 days (137.8 weeks). Discontinuation rates were low, and secukinumab had a favourable safety profile, consistent with previous reports. Exposure-adjusted incidence rates for serious infections, Candida infections, Crohn's disease, ulcerative colitis, malignant/unspecified tumours, and adjudicated major adverse cardiac events were 1.1, 0.4, 0.5, 0.1, 0.5 and 0.7 per 100 subject-years, respectively. CONCLUSIONS: Secukinumab provided sustained efficacy in signs, symptoms and physical function in subjects with AS over 3 years. No new safety signals were observed.