Ixekizumab Improves Symptoms for Patients With Radiographic Axial Spondyloarthritis

Patients with radiographic axial spondyloarthritis (r-axSpA) who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced that were treated with ixekizumab had improvement in the Assessment of Spondyloarthritis International Society (ASAS) response domains as well as other patient-reported outcomes, according to a study published in BCM Rheumatology.¹

“Understanding the role of ixekizumab on the impact of achieving ASAS40 through improvements in PROs described herein will allow physicians to translate a higher ASAS achievement to the improvements in the signs and symptoms reported by their patients, directly affecting a patients’ overall function clinical outcome,” investigators stated.

In both the COAST-V and COAST-W phase 3 randomized controlled trials, patients received a starting dose of either 80 mg or 160 mg of ixekizumab, placebo for the first 16 weeks, or 40 mg of adalimumab in the reference arm of the COAST-V study. Eligible patients were aged 18 years or older, fulfilled ASAS criteria for axSpA, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDI) of ≥4, and a total back pain score of ≥4 according to a numeric rating scale (NRS) with inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs).

Efficacy and safety were analyzed for those receiving the drug either every 2 weeks (Q2W) or 4 weeks (Q4W) and compared with placebo for the first 16 weeks or a dose double-blind extended treatment protocol for 1 year with the goal of assessing the proportion of patients achieving ASAS40 by week 16. Additional endpoints were ASAS20 and ASAS partial remission, as well as changes from baseline regarding spinal pain, function, fatigue, sleep quality, and stiffness. For those in the double-blind extended treatment cohort, patients were assigned to either continued ixekizumab treatment or replaced adalimumab or placebo with ixekizumab from week 16 to 52.

The Bath Ankylosing Spondylitis Functional Index (BASFI) evaluated function, whereas as stiffness and fatigue were determined using BASDI and NRS. ASAS response was scored on a scale of 0 to 10 and sleep quality was analyzed by the Jenkins Sleep Evaluation Questionnaire. At 1 year, data was pooled across all treatment groups and information on patient-reported outcomes (PROs) was collected and categorized into 3 categories: ASAS20 non-responders, ASAS20 but not ASAS40 responders, and ASAS40 responders.

A total of 341 bDMARD-naïve and 315 TNFi-experienced participants were evaluated in the placebo-controlled period for 16 weeks and 329 bDMARD-naïve and 281 TNFi-experienced patients were included in the extended treatment period through week 52.

Improvements were seen in all response domains when comparing ASAS40 responders with ASAS20 non-responders. The highest values were seen in the function and fatigue sectors. A 7.3-fold improvement was seen in patient global disease activity (PtGA), a 4.7-fold improvement in spinal pain, a 5.0-fold improvement in function, and a 3.5-fold improvement was observed in stiffness. When comparing the placebo group with the ixekizumab group, improvements were also noted and remained consistent within the 52-week trial periods.

A significantly larger improvement was observed in the PROs of PtGA. TNFi-experienced patients who achieved ASAS40 had a greater improvement when compared with those who were ASAS non-responders, including a 5.2-fold improvement in PtGA, a 4.6-fold improvement in spinal pain, a 10.5-fold improvement in function, and a 3.6-fold improvement in stiffness. In general, ixekizumab-treated patients had greater improvements in PtGA, pain, function, and stiffness as well.

The study was strengthened by enrolling patients with r-axSpA on a global scale and conducting regular follow-ups for 1 year. However, it was limited by the post hoc association analyses which compared ASAS treatment and PROs as well as the small number of patients who were ASAS2o responders.

“Post hoc analysis demonstrated the sustained and consistent effectiveness of ixekizumab in r-axSpA patients who achieved ASAS40 compared with patients who achieved ASAS20 or ASAS20 non-responders providing greater improvements in clinically relevant PROs including PtGA, spinal pain, spinal pain at night, function, stiffness, fatigue, and sleep quality through 1 year of treatment,” investigators concluded. “Striving to reach an ASAS40 level of improvement will translate to better clinical disease management and improvement in common symptoms and patient quality of life.”

Reference:

Deodhar AA, Mease PJ, Rahman P, et al. Ixekizumab improves spinal pain, function, fatigue, stiffness, and sleep in radiographic axial Spondyloarthritis: COAST-V/W 52-week results. BMC Rheumatol. 2021;5(1):35. Published 2021 Sep 20. doi:10.1186/s41927-021-00205-3