Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis: results from the 52-week, Phase III China-centric study, MEASURE 5

Abstract

Background: Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study.

Methods: MEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China vs. non-China).

Results: Of 458 patients (secukinumab 150 mg, N = 305; placebo, N = 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16 vs. placebo (58.4% vs. 36.6%; P < 0.0001); corresponding rate in the Chinese population was 56.0% vs. 38.5% (P < 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52.

Conclusions: Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations.

Trial registration: ClinicalTrials.gov, NCT02896127; https://ichgcp.net/clinical-trials-registry/NCT02896127?term=NCT02896127&draw=2&rank=1.

Conflict of interest statement

Dr. Feng Huang, Dr. Fei Sun, Dr. Wei-Guo Wan, Dr. Li-Jun Wu, Dr. Ling-Li Dong, Dr. Xiao Zhang, and Dr. Tae-Hwan Kim declare no conflict of interest. Dr. Raj Sengupta received grants, honoraria, and expenses for attendance at advisory board meetings or conferences and for giving lectures from AbbVie, Celgene Corporation, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Ladislav Šenolt received research grants from AbbVie; speaker's honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, and UCB; expenses for attendance at advisory board meeting from AbbVie, Bristol-Myers Squibb, Celgene Corporation, Merck Sharp and Dohme, Novartis, Pfizer, Roche, and UCB; received honoraria for clinical trials from AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Novartis, Pfizer, Takeda, and UCB. Yi Wang, Hao-Min Qiu, Brian Porter, and Sibylle Haemmerle are employees of Novartis and hold Novartis stock.

Figures

Figure 1

Study design of MEASURE 5. The patients were stratified at randomization according to the region (China [N = 327] and non-China [N = 131; Czech Republic, Republic of Korea and UK]). An end of treatment visit at Week 52 and a post-treatment follow-up visit at Week 60 were done after the last study treatment administration for all patients (regardless of whether they completed the entire study as planned or discontinued prematurely). FU: Follow-up; N: Number of randomized patients; q4wk: Every 4 weeks, R: Randomization; s.c.: Subcutaneous; SEC: Secukinumab.

Figure 2

Patient disposition through Week 52. A total of 563 patients were screened, of whom 458 (81.3%) were randomized (secukinumab 150 mg: N = 305 and placebo: N = 153). The most frequent reason for screening failure was history of ongoing, chronic or recurrent infectious disease (32.4% of screen failures). The majority (>90%) of patients completed Week 52 in both overall and Chinese populations. N: Number of randomized patients.

Figure 3

ASAS20 (A) and ASAS40 (B) response rates in patients with active AS through Week 16. ∗P < 0.0001; †P < 0.001; ‡P < 0.01; §P < 0.05 vs. placebo (P values are adjusted for the overall population and unadjusted for the Chinese population). Missing values were imputed as non-response (NRI). AS: Ankylosing spondylitis; ASAS: Assessment of SpondyloArthritis international Society; N: Total number of randomized patients; NRI: Non-responders imputation.

Figure 4

ASAS20 (A) and ASAS40 (B) response rates in patients with active AS at Week 16 by baseline TNFi therapy status. ∗P < 0.0001; †P < 0.001; ‡P < 0.01; §P < 0.05 vs. placebo (P values are un-adjusted for all). Missing values were imputed as non-response (NRI). AS: Ankylosing spondylitis; ASAS: Assessment of SpondyloArthritis international Society; IR: inadequate responder; N: Total number of randomized patients; NRI: Non-responders imputation; TNFi: Tumor necrosis factor inhibitor.