Clinical evidence for IL-17A blockade in psoriatic arthritis and axial spondyloarthritis

IL-17A blockade with ixekizumab or secukinumab demonstrates robust and sustained efficacy for both psoriatic arthritis and axial spondyloarthritis, with clinically meaningful improvements in joint symptoms, axial manifestations, and skin disease, accompanied by an acceptable safety profile characterized primarily by increased mucocutaneous candida infections.

Abstract

IL-17A blockade demonstrates consistent efficacy across the spectrum of psoriatic arthritis and axial spondyloarthritis in multiple randomized controlled trials. In radiographic axial spondyloarthritis, ixekizumab achieved ASAS40 response rates of 48-52% at week 16 versus 18% with placebo, while secukinumab showed approximately 60% ASAS20 responses across trials. In non-radiographic axial spondyloarthritis, ixekizumab demonstrated ASAS40 rates of 30-40% versus 13-19% with placebo at weeks 16 and 52. For psoriatic arthritis, meta-analytic evidence shows pooled ACR20 response relative risks of 2.04 (95% CI: 1.79-2.33), with individual trials reporting ACR20 rates of 50-62% versus 17-30% with placebo at week 24. Skin manifestations improved substantially, with PASI 75 response rates of 69-75% versus 7.5% placebo at week 12. TNF-naive patients showed greater absolute benefits than TNF-experienced populations, though both groups demonstrated significant improvements. The safety profile was generally favorable, with treatment-emergent adverse event rates of 57-77% and low serious adverse event rates (6% or less). Candida infections occurred more frequently with IL-17A inhibition (4.7% with secukinumab 300 mg), though most were mild to moderate. Discontinuation rates due to adverse events were low (2.4%), and treatment discontinuation rates were actually lower in IL-17A inhibitor groups versus placebo (RR 0.54). These data establish IL-17A blockade as an effective therapeutic option for both psoriatic arthritis and axial spondyloarthritis with an acceptable benefit-risk profile.

Methods

We analyzed 10 sources from an initial pool of 200, using 7 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.

We ran this query: “Clinical evidence for IL-17A blockade in psoriatic arthritis and axial spondyloarthritis”

The search returned 200 total results from Elicit.

Screening

We screened in sources based on their abstracts that met these criteria:

• Population: Does the study include patients diagnosed with psoriatic arthritis and/or axial spondyloarthritis?
• Intervention: Does the study involve IL-17A blockade therapy (secukinumab, ixekizumab, or other IL-17A inhibitors)?
• Study Design: Is the study design a randomized controlled trial, controlled clinical trial, systematic review, or meta-analysis?
• Clinical Outcomes: Does the study report clinical outcomes such as disease activity measures, functional assessments, quality of life, radiographic progression, or safety outcomes?
• Age Group: Does the study include adult patients (≥18 years)?
• Sample Size: Does the study have an adequate sample size (≥10 participants) and is it NOT a case report or case series?
• Publication Type: Is this a full-text publication (not just a conference abstract)?

We considered all screening questions together and made a holistic judgement about whether to screen in each paper.

Results

Characteristics of Included Studies

The review included 10 sources comprising 7 primary randomized controlled trials (RCTs), 2 systematic reviews/meta-analyses, and 1 narrative review.

Joint and Axial Efficacy Outcomes

Axial Spondyloarthritis Studies

The ixekizumab COAST-V trial in radiographic axial SpA demonstrated superior efficacy over placebo at week 16, with ASAS40 response rates of 52% (ixekizumab Q2W), 48% (ixekizumab Q4W), 36% (adalimumab), and 18% (placebo). Both ixekizumab dosing regimens achieved statistical significance versus placebo (p<0.0001).

In non-radiographic axial SpA (COAST-X), ixekizumab showed sustained efficacy with ASAS40 responses at week 16 of 40% (Q2W) and 35% (Q4W) versus 19% placebo, and at week 52 of 31% (Q2W) and 30% (Q4W) versus 13% placebo. Both primary endpoints were statistically significant (p≤0.0037).

Psoriatic Arthritis Studies

The ACR response rates demonstrated consistent efficacy of IL-17A inhibition in PsA. In the Mease et al. 2015 trial, secukinumab achieved ACR20 response rates at week 24 of 50.0% (150 mg) and 50.5% (75 mg) versus 17.3% placebo (p<0.001).

Skin Efficacy Outcomes

Skin outcomes were primarily reported in PsA trials. The SPIRIT-P1 trial showed robust PASI 75 response rates at week 12 of 75.3% (ixekizumab Q4W) and 69.5% (Q2W) versus 7.5% placebo, with responses observed as early as week 4. Nearly half of patients with ≥3% affected body surface area achieved complete psoriasis clearance.

Safety Profile

Overall Adverse Events and Infections

The most common adverse events across trials were nasopharyngitis, upper respiratory tract infections, and injection site reactions. Infections showed similar frequencies across treatment groups.

Serious Adverse Events and Cardiovascular Events

Serious adverse event rates were generally low.

• The MAXIMISE trial reported serious adverse events in 6% of secukinumab-treated patients.

Synthesis

Efficacy Across Disease Subtypes

The evidence demonstrates consistent efficacy of IL-17A blockade across the spectrum of psoriatic arthritis and axial spondyloarthritis.

References

P. Mease, I. McInnes, B. Kirkham, A. Kavanaugh, P. Rahman, and 7 more(2015).Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. New England Journal of Medicine
P. Mease, I. McInnes(2016).Secukinumab: A New Treatment Option for Psoriatic Arthritis. Rheumatology and Therapy
D. van der Heijde, James Cheng-Chung Wei, M. Dougados, P. Mease, A. Deodhar, and 10 more(2018).Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and. The Lancet

The content demonstrates efficacy and safety of IL-17A blockade in treating psoriatic arthritis and axial spondyloarthritis.