Systematic review and network meta-analysis of biologics and small molecules for scalp psoriasis

Scalp psoriasis is a recalcitrant phenotype that imposes a substantial burden on quality of life. While the therapeutic landscape has expanded, comprehensive comparative evidence for newer biologics and small molecules in this specific manifestation remains limited.

To systematically compare the short-term efficacy, safety and tolerability of biologics and small molecules for scalp psoriasis.

We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) identified from MEDLINE, EMBASE, CENTRAL and other databases from inception to October 2025. The primary efficacy endpoint was scalp clearance (defined as Scalp Physician's Global Assessment [scPGA] 0/1, scalp-specific Investigator's Global Assessment [ss-IGA] 0/1 or Psoriasis Scalp Severity Index [PSSI] 90/100) at Weeks 12-16. Safety outcomes included all-grade adverse events (AEs) and serious AEs (SAEs). Tolerability was defined as the discontinuation rate due to AEs. Data were synthesized using a frequentist random-effects model.

Sixteen RCTs comprising 10,266 patients were included. All active agents demonstrated statistically significant improvements versus placebo. Ixekizumab every 2 weeks (Q2W) (odds ratio [OR] 54.02; 95% confidence interval [CI] 39.38-74.09) and brodalumab (OR 53.16; 95% CI 15.47-182.69) ranked highest for scalp clearance, followed by ixekizumab every 4 weeks (Q4W), guselkumab and bimekizumab. Regarding safety, secukinumab, tildrakizumab, apremilast, deucravacitinib and both ixekizumab regimens were associated with significantly higher incidences of all-grade AEs compared with placebo, whereas SAE risks were non-significant across interventions. Apremilast was the only agent associated with significantly higher discontinuation rates due to AEs (OR 1.62; 95% CI 1.09-2.42).

Interleukin-17 inhibitors, particularly ixekizumab and brodalumab, demonstrated the most significant short-term scalp clearance. Guselkumab showed a favourable balance of efficacy, safety and tolerability. Serious adverse events were not significantly increased with any agent. Collectively, these findings provide up-to-date comparative evidence to inform the selection of systemic therapies for scalp psoriasis.