A secukinumab dose-escalation study in patients with ankylosing spondylitis not achieving inactive disease after 16 weeks of treatment

Abstract

Objective: To investigate the clinical response at week 52 in patients with AS who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16.

Methods: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease [AS Disease Activity Score (ASDAS) <1.3] at both week 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs) through week 52.

Results: Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS <1.3. The incidence of TEAEs was similar in both groups through week 52. No new safety signals were observed.

Conclusion: Patients with AS who did not achieve ASDAS <1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation.

Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03350815.

Keywords: AS; dose escalation; secukinumab.

Figure 1.

Design of the ASLeap study. ^aSecukinumab administered as a single injection for secukinumab 150 mg and administered as 2 injections of the 150-mg dose for secukinumab 300 mg. ^bPlacebo administered SC 1 mL as per double-dummy design to maintain blinding at week 16 randomization. ^cTo support the integrity of the blind for the randomized inadequate response group, the patients with adequate response were also dose blinded between week 16 and 48 and received a single matching placebo injection with their secukinumab 150-mg injection. ^dNo change or an increase (worsening) from baseline in total ASDAS at either week 12 or 16. ASDAS: Ankylosing Spondylitis Disease Activity Score; BL: baseline; Q4W: every 4 weeks; R: randomization; SC: subcutaneous

Figure 2.

Achievement of binary outcomes in Treatment Period 2 among inadequate responders in Treatment Period 1 (Full Analysis Set; non-responder imputation). ASAS: Assessment of SpondyloArthritis international Society; ASDAS: AS Disease Activity Score

Figure 3.

Achievement of ASAS20, ASAS40, BASDAI50, ASDAS improvement of ≥1.1 and ASDAS inactive disease up to week 52. Proportions of patients achieving binary outcomes up to week 52 using week 0 as baseline (Full Analysis Set; non-responder imputation). ^aThese data correspond to the full analysis set of patients randomized in Treatment Period 2; the achievement of ASDAS inactive disease (<1.3) is absolute and not calculated based on baseline disease activity. ASAS: Assessment of SpondyloArthritis international Society; ASDAS: AS Disease Activity Score