Ixekizumab Improves Fatigue in Patients With Non-Radiographic Axial Spondyloarthritis

Ixekizumab treatment improved sleep, work productivity, and activity impairment in patients with non-radiographic axial spondyloarthritis (nr-axSpA) and results were sustained and consistent through week 52, according to a study published in BCM Rheumatology.¹

“Many patients with axSpA who receive treatment still experience disease-related burdens in different aspects of health-related quality of life (HRQoL),” investigators stated. “While tumor necrosis factor inhibitors (TNFi) have been found to improve axSpA patients’ HRQoL, not all patients receiving TNFi tolerate or respond to treatment, suggesting that treatments with different mechanisms of action may be indicated in some patients.”

COAST-X (NCT02757352) was a 52-week, phase 3, multicenter, randomized, placebo-controlled trial designed to evaluate 80 mg ixekizumab, a monoclonal antibody targeting interleukin-17A, given every 2 or 4 weeks in patients with nr-axSpA. Eligible patients had a clinical diagnosis of nr-axSpA, met Assessment of SpondyloArthritis International Society (ASAS) criteria, and had active disease despite non-steroidal anti-inflammatory drugs (NSAIDs) therapy.

During the trial, patients were allowed to continue any background medications, which could be adjusted from Weeks 16 to 44. They could also switch to ixekizumab Q2W or tumor necrosis factor inhibitors (TNFis).

Patients were randomized to receive placebo Q2W (n = 105), 80 mg ixekizumab Q4W (n = 96), or 80 mg ixekizumab Q2W (n = 102) by subcutaneous injection.

Sleep quality was determined using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asked questions related to waking up throughout the night, trouble falling and remaining asleep, waking up too early, or being affected by fatigue during the day. This was measured at baseline and Weeks 8, 16, 36, and 52.

Activity impairment and work productivity was analyzed via the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis (WPAI-SpA). This evaluated employment status, missed hours of work, hours worked, productivity during the day, and how SpA impacted activities outside of work. Activity impairment was included regardless of work status, however, absenteeism, presenteeism, and work impairment was recorded only for those reporting paid work. These scores were measured at baseline and Weeks 16 and 52.

A total of 303 patients were included in the study, with a mean age of 40.3 years, and a mean duration of nr-asSpA symptoms of 10.7 years. Approximately 64% of participants reported either part- or full-time employment.

Patients receiving both ixekizumab Q4W and Q2W had significantly greater improvements in JSEQ when compared with the placebo cohort at Week 36 (p = 0.015 and p = 0.002 for ixekizumab Q4W and Q2W, respectively) and results remained through the end of the trial. Patients in both ixekizumab groups also had more improvement in areas of absenteeism, presenteeism, and work impairment at Weeks 16 and 52 when compared with those receiving the placebo.

The difference in least square mean (LSM) changes at baseline for presenteeism were greater in the ixekizumab Q4W cohort when compared with placebo at Weeks 16 (− 12.7 [SE 4.6; p = 0.007]) and Week 52 (− 13.6 [SE 4.6; p = 0.003]). The LSM difference for work impairment for ixekizumab Q4W and placebo was − 12.3 (SE 4.9) at Week 16 (p = 0.014) and − 13.8 (SE 4.8) at Week 52 (p = 0.005).

LSM differences in activity impairment was also significantly greater in ixekizumab Q4W when compared with placebo at Weeks 16 − 10.4 (SE 3.4; p = 0.003), and the LSM difference between ixekizumab Q2W and placebo was − 9.1 (SE 3.4; p = 0.007). At Week 52, the difference between the ixekizumab Q2W and placebo was − 10.6 (SE 3.7; p = 0.004), and the difference between ixekizumab Q2W and placebo was − 10.0 (SE 3.6; p = 0.006).

The inclusion of a placebo allowed for a true comparison of the effects of ixekizumab in this diverse patient population from multiple global regions. Additionally, patients in the COAST-X trial had disease symptoms for over 10 years before developing r-axSpA. Using validated tools like JSEQ and WPAI-SpA further strengthened the study.

However, a limited number of patients were included in the WPAI-SpA assessment, as it is required of participants to report part- or full-time employment to assess absenteeism, presenteeism, and overall work impairment. Another limitation was that the study did not included specific predefined criteria to switch patients to open label ixekizumab.

“The results of this study show improvements in sleep, work productivity, and activity impairment and are consistent with previously reported results demonstrating the efficacy of ixekizumab in treating nr-axSpA,” investigators concluded. “Collectively, these results suggest treatment with ixekizumab can improve patient-reported outcomes as well as overall HRQoL in the specific context of nr-axSpA.”

Reference:

Deodhar A, Mease P, Marzo-Ortega H, et al. Ixekizumab improves sleep and work productivity in patients with non-radiographic axial spondyloarthritis: results from the COAST-X trial at 52 weeks. BMC Rheumatol. 2021;5(1):50. Published 2021 Sep 25. doi:10.1186/s41927-021-00218-y