Elicit: IL-17A Blockade in Psoriatic Arthritis and Axial Spondyloarthritis
IL-17A Blockade in Psoriatic Arthritis and Axial Spondyloarthritis
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”
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?
- 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?
- Age Group: Does the study include adult patients (≥18 years)?
- Sample Size: Does the study have an adequate sample size (≥10 participants)?
- Publication Type: Is this a full-text publication?
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.
| Study | Full text retrieved? | Study design | Duration | Sample size | Funding | Geographic scope |
|---|---|---|---|---|---|---|
| van der Heijde et al., 2018 | Yes | Phase III RCT | 52 weeks with optional 2-year extension | 341 randomized | Eli Lilly and Company | 84 sites in 12 countries |
| Deodhar et al., 2019 | No | Phase III RCT | 52 weeks | 303 randomized (105 placebo, 96 ixekizumab Q4W, 102 ixekizumab Q2W) | Eli Lilly and Company | 107 sites in 15 countries |
| Baeten et al., 2013 | No | Phase II proof-of-concept RCT | Week 6 efficacy, week 28 safety | 30 randomized (24 secukinumab, 6 placebo), 29 completed | Novartis | 8 sites in Europe |
| Baraliakos et al., 2020 | Yes | Phase 3b RCT | 52 weeks | 498 randomized, 425 completed (85%) | Novartis | 97 centers in Europe, Russia, Israel |
| Naik et al., 2017 | Yes | Systematic review and meta-analysis of RCTs | 12-24 weeks | 1,718 in treatment arm, 840 in placebo arm | Industry-sponsored | Not reported |
| Mease et al., 2015 | No | Phase III RCT | 52 weeks | 606 randomized | Novartis Pharma | Not reported |
| Mease & McInnes, 2016 | Yes | Narrative review of phase III trials | At least 52 weeks | Not reported | Novartis Pharma | Not reported |
| González Alonso et al., 2022 | Yes | Systematic review and meta-analysis of RCTs | Week 12 primary timepoint | 23 studies included | AbbVie | Not reported |
| Aparicio et al., 2021 | Yes | Narrative review of phase III trials and real-world studies | Up to 5 years | Not reported | Novartis | Not reported |
| Mease et al., 2016 | Yes | Phase III RCT (SPIRIT-P1) | 24 weeks double-blind, 3 years total | 417 randomized, 382 completed 24 weeks | Eli Lilly and Company | Not reported |
The primary studies enrolled biologic-naive or biologic-experienced patients with active disease.
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) and 48% (ixekizumab Q4W) versus 18% placebo. 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 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.
Safety Profile
The most common adverse events across trials were nasopharyngitis, upper respiratory tract infections, and injection site reactions. Serious infections occurred at low rates. Candida infections emerged as a recognized adverse event with IL-17A blockade.
Synthesis
The evidence demonstrates consistent efficacy of IL-17A blockade across the spectrum of psoriatic arthritis and axial spondyloarthritis, with some important distinctions based on disease phenotype and prior treatment exposure.