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. More on methods.

Records from Elicit search

• n = 200

Papers screened using:

• Population

• Intervention

• Study Design

• Clinical Outcomes

• Age Group

• Sample Size

• Publication Type

• n = 200 Papers screened out

• n = 190 Papers included for extraction

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.

We retrieved 200 papers most relevant to the query for screening.

Screening

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

• Population: Patients diagnosed with psoriatic arthritis and/or axial spondyloarthritis.
• Intervention: Study involves IL-17A blockade therapy.
• Study Design: Randomized controlled trial or systematic review/meta-analysis.
• Clinical Outcomes: Reports disease activity measures, functional assessments, quality of life, radiographic progression, or safety outcomes.
• Age Group: Adult patients (≥18 years).
• Sample Size: Adequate sample size (≥10 participants).
• Publication Type: Full-text publication.

Data extraction

Data extracted included:

• Study Design: Details of the study type, duration, sample size, funding source.
• IL-17A Agent: Specific agent name, dosage, route, and treatment period.
• Patient Population: Relevant patient characteristics, diagnosis, prior biologic exposure, demographics.
• Comparator Groups: Control details, randomization ratio, allowed medications.
• Joint Efficacy Outcomes: ACR20/50/70 response rates, physical function measures, radiographic progression measures, and statistical significance.
• Skin Efficacy Outcomes: PASI response rates and other skin-related metrics.
• Safety Profile: Adverse events, serious adverse events, infections, cardiovascular events, malignancies.
• Risk of Bias: Study quality indicators such as randomization method and adequacy, allocation concealment, blinding, completeness of follow-up, selective outcome reporting concerns.

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. Four studies evaluated ixekizumab, five evaluated secukinumab, and two meta-analyses evaluated multiple IL-17 inhibitors.

The studies enrolled biologic-naive or biologic-experienced patients with active disease.

Joint and Axial Efficacy Outcomes

Axial Spondyloarthritis Studies

The ixekizumab COAST-V trial demonstrated superior efficacy over placebo at week 16, with ASAS40 response rates of 52% (ixekizumab Q2W), 48% (ixekizumab Q4W) vs 18% placebo, achieving statistical significance (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, also statistically significant (p≤0.0037).

Psoriatic Arthritis Studies

The ACR response rates demonstrated consistent efficacy of IL-17A inhibition in PsA trials, with significant results across different dosing regimens and timeframes.

Safety Profile

Overall Adverse Events and Infections

Candida and Opportunistic Infections

Candida infections emerged as a recognized adverse event with IL-17A blockade.

Serious Adverse Events and Cardiovascular Events

Serious adverse event rates were generally low across studies.

Malignancies, Laboratory Abnormalities

Malignancy rates were low, with particular concerns addressed in past trials.

Conclusion

The evidence demonstrates consistent efficacy of IL-17A blockade across the spectrum of psoriatic arthritis and axial spondyloarthritis, highlighting differences based on disease phenotype and prior treatment exposure.