ASLeap: Higher Dose Secukinumab in Ankylosing Spondylitis Save

Ankylosing spondylitis (AS) patients not responding to usual dosing with secukinumab (150 mg) after 16 weeks were dose escalated to secukinumab (SEC) 300 mg, but failed to show improvement by week 52. 

The ASLeap trial was a randomized, double-blind, parallel-group, multicentre, phase 4 trial, where patients initially (Treatment Period 1) received 16 weeks of open-label secukinumab 150 mg. If at weeks 12 and 16 patients had an inadequate response (defined as ASDAS <1.3, they were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy outcome was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. 

A total of 322 AS patients were treated with SEC for 16 weeks, with two-thirds (64.3%) having inadequate response. Such inadequate responders were randomized to receive either SEC 300 mg (n = 101) or 150 mg (n = 105) SC. 

With roughly 84% of patients completing the trial, week 52 results showed that very few patients in either group (8.8% vs 6.7%) achieved ASDAS <1.3.  Adverse events were also similar in between groups through week 52.

Escalating the SEC dose after a 16 week non-response to 150 mg q 4 weeks failed to improve outcomes in these AS patients. Reasons for this are unclear but may relate host factors or the stringency of the outcome measure. Nonetheless these data suggest that change in therapy may be more appropriate than dose escalation.