Ixekizumab COASTs through r-axSpA with sustained efficacy, safety

Two phase III trials reflect the sustained efficacy and safety of the bDMARD* ixekizumab in bDMARD-naïve (COAST-V) or TNFi**-experienced (COAST-W) adults with active radiographic axial spondyloarthritis (r-axSpA), also known as ankylosing spondylitis (AS).

“[In both COAST trials,] the significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks … [R]esults were similar between two ixekizumab regimens across endpoints … Safety findings were consistent with the known safety profile of ixekizumab,” said the researchers. [Lancet 2018;392:2441-2451; Arthritis Rheumatol 2019;71:599-611]

AS is associated with limited mobility, progressive disability, and reduced quality of life. [Lancet 2017;390:73-84; J Med Econ 2012;15:1054-1063] The findings underline the potential of ixekizumab to be a long-term treatment alternative in this setting, regardless of TNFi history, noted the researchers.

In COAST-V, 341 bDMARD-naïve adults were randomized 1:1:1:1 to ixekizumab 80 mg Q2W or Q4W, adalimumab 40 mg Q2W, or placebo. In COAST-W, 316 adults who discontinued TNFis due to intolerance or inadequate response were randomized 1:1:1 to ixekizumab Q2W or Q4W, or placebo. At week 16, patients receiving ixekizumab continued their assigned regimen, while those receiving placebo and adalimumab were rerandomized 1:1 to ixekizumab Q2W or Q4W through week 52 (starting dose of 160 mg [placebo] and 80 mg [adalimumab]). [Ann Rheum Dis 2020;79:176-185]

In COAST-V, ASAS40*** response rates at week 52 were similar for ixekizumab Q2W and Q4W (51 percent and 53 percent), which echoed the week 16 rates (52 percent and 48 percent). A similar trend was observed among those who transitioned from placebo and adalimumab (47 percent and 51 percent), but these were much improved from week 16 (19 percent and 36 percent).

In COAST-W, ASAS40 response rates at week 52 were similar across subgroups (31, 34, and 39 percent for ixekizumab Q2W, Q4W, and placebo-ixekizumab, respectively). As in COAST-V, the rates for ixekizumab Q2W and Q4W paralleled those found at week 16 (31 percent and 25 percent), and improved for those who switched from placebo (14 percent).

“[Collectively, the] response rates in patients rerandomized from placebo rapidly increased to levels consistent with those seen with continuous ixekizumab treatment,” noted the researchers.

Despite the similar results, it should be noted that the responses in COAST-V were numerically higher than in COAST-W. “[This reflects the] more difficult to treat population [in COAST-W who had] more long-standing [and] very active disease (baseline ASDAS^# >4), and >30 percent having failed two prior TNFis.”

Treatment-emergent adverse event (TEAE) rates were similar between COAST-V and COAST-W (61 percent and 64 percent). Most TEAEs were mild or moderate, the most common being nasopharyngitis, injection site reactions, and upper respiratory tract infections. No deaths were reported in either study. “The safety profile of ixekizumab [from] week 16–52 in both [trials] is consistent with that observed during week 0–16,” said the researchers.

Despite the lack of a control arm, the trials exclusively enrolled bDMARD-naïve and TNFi-experienced patients. “[Therefore,] both studies were fully powered for analyses in these populations,” said the researchers.

“[Taken together,] ixekizumab provided sustained and clinically meaningful improvement in the signs and symptoms of active r-axSpA for up to 52 weeks … with a high rate of completion. These findings suggest that ixekizumab could be a treatment option for r-axSpA in [this patient setting],” they concluded.

The additional improvement among ixekizumab recipients who switched from adalimumab is of interest and warrants further exploration, they added.