Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study

Abstract

Objective: Secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks in the phase III MEASURE 2 study. Here, we report longer-term (104 weeks) efficacy and safety results.

Methods: Patients with active AS were randomized to subcutaneous secukinumab 150 mg, 75 mg, or placebo at baseline; weeks 1, 2, and 3; and every 4 weeks from week 4. The primary end point was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16. Other end points included ASAS40, high-sensitivity C-reactive protein, ASAS5/6, Bath Ankylosing Spondylitis Disease Activity Index, Short Form 36 health survey physical component summary, ASAS partial remission, EuroQol 5-domain measure, and Functional Assessment of Chronic Illness Therapy fatigue subscale. End points were assessed through week 104, with multiple imputation for binary variables and a mixed-effects model repeated measures for continuous variables.

Results: Of 219 randomized patients, 60 of 72 (83.3%) and 57 of 73 (78.1%) patients completed 104 weeks of treatment with secukinumab 150 mg and 75 mg, respectively; ASAS20/ASAS40 response rates at week 104 were 71.5% and 47.5% with both secukinumab doses, respectively. Clinical improvements with secukinumab were sustained through week 104 across all secondary end points. Across the entire treatment period (mean secukinumab exposure 735.6 days), exposure-adjusted incidence rates for serious infections and infestations, Crohn's disease, malignant or unspecified tumors, and major adverse cardiac events with secukinumab were 1.2, 0.7, 0.5, and 0.7 per 100 patient-years, respectively. No cases of tuberculosis reactivation, opportunistic infections, or suicidal ideation were reported.

Conclusion: Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS, with a safety profile consistent with previous reports.

Trial registration: ClinicalTrials.gov NCT01649375.

© 2017 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Figures

Figure 1

Patient disposition through 104 weeks of secukinumab treatment. s.c. = subcutaneous.

Figure 2

Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) (A) and ASAS40 (B) response rates from baseline by treatment groups over 104 weeks. All data through week 104 calculated with multiple imputation for patients originally randomized to secukinumab. s.c. = subcutaneous.

Figure 3

Mean change in Bath Ankylosing Spondylitis Disease Activity Index score from baseline by treatment groups through week 104. Least squares mean change using mixed‐effects model repeated measures through week 104 for patients originally randomized to secukinumab. s.c. = subcutaneous.

Figure 4

Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) (A) and ASAS40 (B) response rates at weeks 16, 52, and 104 by anti–tumor necrosis factor (anti‐TNF) status. Missing data were imputed as nonresponses at week 16 (nonresponders imputation). Observed data are shown at weeks 52 and 104 (shaded background). P values are versus placebo at week 16. s.c. = subcutaneous; IR = inadequate response; † = P < 0.001; ‡ = P < 0.05; § = P < 0.01.