Ixekizumab Improves Back Pain, Morning Stiffness in Patients with PsA

Patients with active psoriatic arthritis (PsA) with axial manifestation receiving ixekizumab treatment exhibited greater improvements in axial symptoms, such as back pain and morning stiffness, according to a study published in Therapeutic Advances in Musculoskeletal Disease.¹

Atul Deodhar, MD, MRCP

Credit: Oregon Health & Science University

Axial manifestations occur in 5 – 28% of patients with early-stage PsA and 25 – 70% of patients with established PsA. Risk factors include peripheral joint radiographic damage, an increased erythrocyte sedimentation rate, and being positive for human leukocyte antigen (HLA)-B27.² Ixekizumab targets interleukin (IL)-17A, a cytokine linked to the pathogenesis of PsA.

“At present, there is no defined criteria to classify patients with PsA and axial involvement, and much of what is known about treatment has been derived from studies in radiographic-axial spondyloarthritis (r-axSpA),” wrote Atul Deodhar, MD, MRCP, professor of medicine and medical director of rheumatology clinics at the Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, and colleagues.

“The 2022 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment guidelines for PsA recommend the use of IL-17 inhibitors, tumor necrosis factor inhibitors (TNF), and Janus kinase inhibitors (JAK).”

In the post hoc analysis comprised of 2 pooled phase 3, placebo-controlled, randomized, double-blind clinical trials (SPIRIT-P1 and SPIRIT-P2), investigators evaluated the efficacy of ixekizumab in reducing axial symptoms in this patient population up to 52 weeks. Eligible patients had back pain and morning stiffness at baseline and those receiving ixekizumab 80 mg every 4 weeks (Q4W) or placebo were included in the current analysis.

Axial manifestations were defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 (back pain) total score ≥4 and a BASDAI Q5 and Q6 (morning stiffness) ≥4 at baseline.

Efficacy of the drug was assessed at week 16, week 24, and week 52 using the specific BASDAI questions, total BASDAI, modified BASDAI (mBASDAI; excluding Q3), 50% improvement in BASDAI (BASDAI50) response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Comparisons were evaluated using logistic regression for categorical endpoints and an analysis of the covariance model for continuous endpoints. Additional analyses evaluated patients aged <45 years and a subset of patients with increased C-reactive protein (CRP).

Of the 313 patients analyzed, 162 were assigned to the ixekizumab cohort and 151 received placebo. The mean age of the total population was 51 years and more female patients exhibited axial manifestations at baseline.

Patients with PsA and back pain experienced a greater disease burden compared with patients without back pain. Significantly greater improvements in back pain and morning stiffness at week 16 and week 24 were observed in patients receiving ixekizumab compared with placebo (both P <.001). Similarly, improvements in BASDAI total scores and individual scores, mBASDAI, and ASDAS were significantly greater in the ixekizumab cohort compared with the placebo cohort.

Further, a greater number of patients receiving ixekizumab achieved BASDAI50 at weeks 16 (P = .005) and 24 (P = .005) and significantly more patients achieved a BASDAI Q2 score improvement of ≥2. Patients aged <45 years with spinal pain and inflammation treated with ixekizumab reported significantly greater improvements in back pain at week 16 (P = .008) and week 24 (P <.001). Comparable results were observed in morning stiffness and effects were sustained at week 52.

Investigators noted a lack of a validated definition of axial PsA as a limitation. However, the study was strengthened by including 2 sensitivity analysis subgroups.

“These data provide clinically relevant information about some of the disease characteristics of patients with PsA and axial manifestations as well as support for using ixekizumab as a potential therapeutic option for these patients,” investigators concluded.

References

1. ^{Deodhar A, Gladman D, Bolce R, et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023;15:1759720X231189005. Published 2023 Aug 24. doi:10.1177/1759720X231189005}
2. ^{Chandran V, Tolusso DC, Cook RJ, et al. Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis. J Rheumatol 2010; 37: 809–815.}