Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo-Controlled Phase III Study

Abstract

Objective: To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA).

Methods: A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non-loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)-naive patients. Safety analyses included all patients who received ≥1 dose of study treatment.

Results: Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported.

Conclusion: Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.

Trial registration: ClinicalTrials.gov NCT02696031.

Figure 1

Patient disposition through week 52. Of 1,583 patients screened, 555 (35.1%) were randomized. A patient can have more than 1 reason for screening failure. The main reasons for screening failure based on inclusion and exclusion criteria are presented in Supplementary Table 3, available on the Arthritis & Rheumatology website at http://onlinelibrary.wiley.com/doi/10.1002/art.41477/abstract. The majority (84–89%) of patients completed week 52. Discontinuations are presented for the whole treatment period from baseline to week 52. ASAS = Assessment of SpondyloArthritis international Society; axSpA = axial spondyloarthritis; LD = with loading; NL = without loading.

Figure 2

Primary and key secondary outcomes through week 52 based on statistical hierarchy. A, Assessment of SpondyloArthritis international Society criteria for 40% improvement (ASAS40) response at week 16 (analysis plan A for European Union [EU] and non‐US region regulatory requirements) and week 52 (analysis plan B for US regulatory requirements) in tumor necrosis factor inhibitor–naive patients randomized to receive secukinumab 150 mg with loading (LD), secukinumab 150 mg without loading (NL), or placebo (primary objective). B, Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in each treatment group through week 16. C, BASDAI criteria for 50% improvement response in each treatment group through week 16. D, Sacroiliac (SI) joint edema score on magnetic resonance imaging (MRI) in the overall population and in the subgroup of patients who were MRI‐positive at screening (defined as the presence of inflammatory lesions in the SI joints on MRI according to the ASAS/Outcome Measures in Rheumatology definition). The mean baseline SI joint edema score was 3.56 in the group with loading and 2.64 in the group without loading in the overall population and 5.23 in the group with loading and 3.48 in the group without loading in the subgroup of patients who were MRI‐positive at screening. For SI joint edema score at week 16, P values were determined by an analysis of covariance model based on multiple imputation (missing at random assumption), and data are presented as the least squares (LS) mean change. Observed data (shaded) for SI joint edema score at week 52 are shown for secukinumab‐treated patients who did not switch treatment. * = P < 0.0001; † = P < 0.001; § = P < 0.01; ‡ = P < 0.05, versus placebo.