Secukinumab Demonstrates Long-Term Safety, Efficacy in Ankylosing Spondylitis

Treatment with secukinumab 150 mg has demonstrated sustained efficacy and a consistent safety profile across multiple domains of ankylosing spondylitis (AS), according to research results published in Rheumatic & Musculoskeletal Diseases Open.¹

Researchers reported end-of-study safety and efficacy results of the MEASURE 1 study (ClinicalTrials.gov Identifier: NCT01863732) of secukinumab therapy in patients with AS. The phase 3, double-blind, randomized, placebo-controlled study took place over 2 years, with a 3-year extension period.² Patients were randomly assigned to receive either 10 mg/kg intravenous secukinumab at baseline and weeks 2 and 4 or placebo. After 2 years, 274 patients entered the extension period and received subcutaneous secukinumab at either 150 mg or 75 mg every 4 weeks thereafter.

Among the total cohort of 371 patients, 230 (62%) who enrolled in the core study completed 5 years of treatment; 230 (84%) of the 274 patients enrolled in the extension study completed 5 years of treatment. Overall, 108 (84%) of the 128 patients in the secukinumab 150 mg group completed 5 years of treatment.

Results indicated that, over 5 years, Assessment of Spondyloarthritis International Society (ASAS)20 and ASAS40 responses were sustained in patients who originally received secukinumab 150 mg therapy (77.6% and 64.5%, respectively). These responses were also sustained in patients who were in the anti-tumor necrosis factor (TNF)-naive and anti-TNF-inadequate responders groups. Among patients in the secukinumab 150 mg group, including those who switched from placebo, ASAS20 and ASAS40 responses at 5 years were 78.6% and 65.2%, respectively. Improvements were sustained across all individual ASAS components.

Secukinumab dose was escalated from 75 mg to 150 mg in 56.2% of patients (n=82) during the study period. ASAS20, ASAS40, ASAS-Partial Remission, ASAS 5/6, and Bath Ankylosing Spondylitis Disease Activity Index 50 responses were all improved in this patient group.

Mean exposure to any dose of secukinumab was 1446.1±631.2 days, with the most common adverse events being nasopharyngitis, headache, diarrhea, and upper respiratory tract infection (incidence rate, >5/100 patient-years; relative frequency, >2%). Candida infections were reported in 5 patients in the secukinumab groups, and 2 cases of opportunistic infections were reported in any secukinumab 75 mg group. Nine patients treated with secukinumab reported inflammatory bowel disease. Investigators identified treatment-emergent antidrug antibodies in 1 patient in the secukinumab 150 mg group, but these antibodies were not associated with abnormal pharmacokinetic profiles or clinically relevant adverse events. A total of 4 deaths were noted during the study period, though none were related directly to the study treatment.

“Secukinumab provided sustained efficacy across multiple domains of AS, including signs and symptoms, physical function and objective markers of inflammation through 5 years,” the researchers concluded. “The results demonstrate that secukinumab is a long-term treatment option for patients with AS for both [patients who are] biologic-naive and for those…who experience an inadequate response or intolerance to anti-TNF agents.”

Disclosures: This study was supported by Novartis Pharma AG, Basel, Switzerland. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures. .

References

1. Baraliakos X, Braun J, Deodhar A, et al. Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study [published online September 3, 2019]. RMD Open. doi:10.1136/rmdopen-2019-001005

2. Baeten D, Sieper J, Braun J, et al. Secukinumab, an interleukin-17a inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373:2534-2548.