IL-17 Inhibitors Top Network Meta-Analysis for Scalp Psoriasis Clearance

Interleukin (IL)-17 inhibitors, particularly ixekizumab and brodalumab, produced the highest short-term rates of scalp clearance among biologics and small molecules used for scalp psoriasis, while the authors noted that the IL-23 inhibitor guselkumab offered the most favorable balance of efficacy, safety, and tolerability, according to a systematic review and network meta-analysis published in the Journal of the European Academy of Dermatology and Venereology.¹

Why Scalp Psoriasis Remains Difficult to Treat

Scalp involvement affects up to 80% of patients with psoriasis and is associated with pruritus, visible scaling, and a disproportionate psychosocial burden. Research presented at the 2025 American Academy of Dermatology Annual Meeting found that among 154 patients with moderate to severe scalp psoriasis, quality of life was substantially impaired across multiple patient-reported outcomes, even in those with less extensive disease elsewhere on the body, suggesting scalp involvement may affect patients out of proportion to total body surface area.² Although several new biologics and oral agents have reached the market, comparative evidence specific to scalp disease has been limited, prompting the investigators to update earlier analyses with newer agents such as bimekizumab and deucravacitinib.¹

The researchers searched MEDLINE, Embase, CENTRAL, Scopus, and Google Scholar through October 30, 2025, identifying 16 randomized clinical trials comprising 10,266 patients. The primary end point was scalp clearance, defined as a Scalp Physician's Global Assessment (scPGA) or scalp-specific Investigator's Global Assessment (ss-IGA) score of 0 or 1, or a 90% or 100% improvement in the Psoriasis Scalp Severity Index (PSSI), at weeks 12 to 16. Safety outcomes included all-grade adverse events (AEs) and serious AEs (SAEs), and tolerability was measured by discontinuation due to AEs. Data were pooled using a frequentist random-effects model.

Ixekizumab and Brodalumab Lead Scalp Clearance

All active agents outperformed placebo. Ixekizumab every 2 weeks ranked highest (odds ratio [OR], 54.02; 95% CI, 39.38-74.09), followed closely by brodalumab (OR, 53.16; 95% CI, 15.47-182.69), ixekizumab every 4 weeks (OR, 37.37; 95% CI, 27.46-50.86), guselkumab (OR, 32.75; 95% CI, 22.98-46.69), bimekizumab (OR, 29.58; 95% CI, 14.44-60.56), and secukinumab (OR, 21.09; 95% CI, 5.80-76.72), although estimates for brodalumab and secukinumab were imprecise, each drawing on a single trial. Adalimumab and ustekinumab showed moderate efficacy; tildrakizumab, risankizumab, and deucravacitinib showed smaller but significant effects; and etanercept (OR, 3.64; 95% CI, 1.86-7.15) and apremilast (OR, 3.56; 95% CI, 2.90-4.37) ranked lowest. The authors suggested the strength of IL-17 blockade may reflect the scalp's immunology, as scalp lesions show higher IL-17A expression and CD8+ T-cell infiltration than lesions at other sites.

Safety and Tolerability Across Biologics and Oral Agents

For all-grade AEs, secukinumab (OR, 2.75; 95% CI, 1.21-6.27), tildrakizumab (OR, 2.02; 95% CI, 1.12-3.65), apremilast, both ixekizumab regimens, and deucravacitinib carried significantly higher rates than placebo. No agent significantly increased the risk of SAEs. Apremilast was the only treatment linked to significantly more discontinuations due to AEs (OR, 1.62; 95% CI, 1.09-2.42), which the authors said likely reflects early gastrointestinal effects. Bimekizumab (OR, 0.24; 95% CI, 0.08-0.78) and ustekinumab (OR, 0.24; 95% CI, 0.06-0.99) were associated with significantly fewer discontinuations. Tildrakizumab and risankizumab could not be included in the tolerability analysis because their trials reported no discontinuations in either arm.

The authors concluded that IL-17 inhibitors appear best suited to patients seeking rapid clearance, while guselkumab offers moderate efficacy with favorable safety and tolerability. Tumor necrosis factor (TNF) inhibitors and oral agents occupied intermediate positions and may remain relevant when biologic use is constrained.

Study Limitations

The researchers acknowledged several limitations. Harmonizing different scalp scoring systems into a single binary end point may have introduced heterogeneity. Notably, both top-ranked agents, ixekizumab and brodalumab, were assessed with the PSSI; excluding those trials left the ranking of the remaining agents unchanged. Findings reflect only weeks 12 to 16, and longer-term rankings may differ, particularly for IL-23 inhibitors, which in plaque psoriasis have shown superior efficacy by weeks 48 to 52. The very large ORs also occurred against a low mean control event rate of 13%, which can exaggerate perceived differences, so the authors supplemented results with number-needed-to-treat estimates. They called for standardized scalp-specific outcome measures and longer-term trials.

References

1. Lai IC, Lee KC, Huang GL, Wu PY. Systematic review and network meta-analysis of biologics and small molecules for scalp psoriasis. J Eur Acad Dermatol Venereol. 2026;40(11):1785-1795. doi:10.1111/jdv.70506
2. Feldman SR, Duval-Modeste A, Foulkes A, et al. Moderate to severe scalp psoriasis is associated with severe impact on quality of life: an analysis of patient-reported outcomes in PSORIATYK SCALP, a scalp-specific phase 3b/4 trial with deucravacitinib. Poster presented at: 2025 American Academy of Dermatology Annual Meeting; March 7-11, 2025; Orlando, FL.