Long-term ixekizumab safe, effective in axial spondyloarthritis

Use of ixekizumab (IXE) for 3 years in patients with axial spondyloarthritis (axSpA) is safe, which is consistent with the previously established long-term safety profile, reports a study. Treatment with IXE results in sustained improvement of disease activity through 156 weeks.

“IXE every 4 weeks (Q4W) demonstrated efficacy across the three pivotal studies (COAST-V, COAST-W, and COAST-X) and one long-term extension study (COAST-Y),” the investigators said. “Almost 70 percent of patients in the COAST program remained on IXE treatment through 3 years.”

Patients in COAST-Y continued with the dose they received at the end of the originating study at week 52: IXE 80 mg either Q4W or every 2 weeks (Q2W). Placebo-treated patients from COAST-X received IXE Q4W in COAST-Y. Those receiving IXE Q4W could be escalated to Q2W at week 116 (week 64 of COAST-Y).

The investigators examined the safety for patients receiving one or more doses of IXE and the efficacy for those receiving at least one dose of IXE Q4W. They then summarized data as observed.

Treatment-emergent adverse events (TEAEs) among the 932 patients who received ≥1 dose of IXE through 3 years occurred at an incidence rate (IR) of 38.0 per 100 patient-years (PYs). Infections (IR, 25.7 per 100 PYs) were the most common TEAE reported, followed by injection site reactions (IR, 7.4 per 100 PYs). Most TEAEs were mild or moderate in severity. [J Rheumatol 2023;50:1020-1028]

Of the TEAEs recorded, 7.1 percent led to treatment cessation (IR, 3.1 per 100 PYs), which is considered low and consistent with what has been previously reported. [Rheumatology 2020;59:3834-3844]

In addition, the rates of inflammatory bowel disease (IBD) remained low in the present safety population. In contrast, a significantly higher proportion of patients with ankylosing spondylitis were diagnosed with comorbid IBD relative to matched controls in an earlier study that used a large US administrative claims data set. [Clin Rheumatol 2018;37:1869-1878]

Long-term efficacy

Notably, all patients treated with IXE Q4W assessed through 3 years achieved sustained improvements in Ankylosing Spondylitis Disease Activity Score, clinically important improvements, and other efficacy endpoints.

The above finding supported previously published results at 2 years in patients from the COAST program and long-term studies of other biologics. [RMD Open 2022;8:e002165; RMD Open 2019;5:e001005; J Rheumatol 2008;35:1346-1353]

Overall, “[t]hese results provide additional evidence to support the fact that patients with axSpA receiving IXE experience long-term safety and sustained improvements in efficacy and patient-reported outcomes at 3 years,” the investigators said.

The current study had certain limitations. First, the dose escalation from IXE Q4W to Q2W was done solely at the investigator’s discretion and with no specific criteria to guide such decision. Second, the observed data while patients were receiving the IXE Q2W escalated dose were not included in the main results, which obscured the definitive analysis of IXE Q4W, since “switching to IXE Q2W placed Q4W responders in the nonresponder imputation category.