Continuing versus withdrawing ixekizumab treatment in patients with axial spondyloarthritis who achieved remission: efficacy and safety results from a placebo-controlled, randomised withdrawal study (COAST-Y)

Abstract

Objectives: The objective of COAST-Y was to evaluate the effect of continuing versus withdrawing ixekizumab (IXE) in patients with axial spondyloarthritis (axSpA) who had achieved remission.

Methods: COAST-Y is an ongoing, phase III, long-term extension study that included a double-blind, placebo (PBO)-controlled, randomised withdrawal-retreatment period (RWRP). Patients who completed the originating 52-week COAST-V, COAST-W or COAST-X studies entered a 24-week lead-in period and continued either 80 mg IXE every 2 (Q2W) or 4 weeks (Q4W). Patients who achieved remission (an Ankylosing Spondylitis Disease Activity Score (ASDAS)<1.3 at least once at week 16 or week 20, and <2.1 at both visits) were randomly assigned equally at week 24 to continue IXE Q4W, IXE Q2W or withdraw to PBO in a blinded fashion. The primary endpoint was the proportion of flare-free patients (flare: ASDAS≥2.1 at two consecutive visits or ASDAS>3.5 at any visit) after the 40-week RWRP, with time-to-flare as a major secondary endpoint.

Results: Of 773 enrolled patients, 741 completed the 24-week lead-in period and 155 entered the RWRP. Forty weeks after randomised withdrawal, 83.3% of patients in the combined IXE (85/102, p<0.001), IXE Q4W (40/48, p=0.003) and IXE Q2W (45/54, p=0.001) groups remained flare-free versus 54.7% in the PBO group (29/53). Continuing IXE significantly delayed time-to-flare versus PBO, with most patients remaining flare-free for up to 20 weeks after IXE withdrawal.

Conclusions: Patients with axSpA who continued treatment with IXE were significantly less likely to flare and had significantly delayed time-to-flare compared with patients who withdrew to PBO.

Keywords: ankylosing; antirheumatic agents; biological therapy; immune system diseases; spondylitis.

Figure 1

COAST-Y study design (A) and patient flow diagram through week 64 of COAST-Y (B). Treatment groups from the originating studies indicate the assigned treatments at the final visit (week 52) of the originating studies. In addition, patient numbers from the originating studies include only those who entered the lead-in period of COAST-Y. The 33 patients receiving placebo at week 52 of the originating studies were from COAST-X. ^aPatients were eligible for entering the randomised withdrawal-retreatment period at week 24 if they achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS) of <1.3 at least once during study visits at week 16 or week 20 and <2.1 at both visits. ^bA total of 157 patients met the remission criteria at week 20, but 2 patients discontinued prior to randomisation at week 24. ^cOne patient in the withdrawn to placebo group who experienced a flare and was retreated discontinued for reason of ‘subject decision’. IXE, ixekizumab; Q2W, every 2 weeks; Q4W, every 4 weeks.

Figure 2

(A) Proportion of flare-free patients through week 64. P value vs withdrawn to placebo: *p<0.05, †p<0.01, ‡p<0.001. (B) Proportion of flare-free patients at week 64 in patient subgroups with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA).

Figure 3

Time-to-flare. P value vs withdrawn to placebo: †p<0.01, ‡p<0.001. IXE, ixekizumab; Q2W, every 2 weeks; Q4W, every 4 weeks.