Children and adults who receive biologics for psoriasis treatment show superior efficacy compared with placebo or standard of care after 3 months of therapy, according to a systematic review and meta-analysis published in Frontiers in Medicine.
Investigators identified randomized controlled trials investigating safety and efficacy of biologics in children (n=5) and adults (n=73) with moderate to severe psoriasis. Pediatric patients had to be candidates for systemic therapy, been poorly controlled by topical therapy, and had to have a history of psoriasis for at least 6 months. Adult patients had slightly more stringent Psoriasis Area Severity Index (PASI) benchmarks, but were less stringent with pretreatment with systemic treatments with phototherapy.
The efficacy endpoints were PASI75 and PASI90 responses in patients randomly assigned to biologic vs control arms and the safety endpoint was the incidence of adverse events between adults vs children with psoriasis treated with biologics. Endpoints were evaluated at weeks 11 or 12 of treatment, which is the standard time for evaluating efficacy and safety of psoriasis treatments. Only studies with monotherapy arms were selected for analysis.
Biologic therapies used in pediatric studies included secukinumab, adalimumab, etanercept, ixekizumab, and ustekinumab. Adult studies included adalimumab, brodalumab, certolizumab, etanercept, ixekizumab, guselkumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab. In pediatric patients, biologics showed significant efficacy compared to placebo (PASI75: risk ratio [RR], 2.02-7.45; PASI90: RR, 4.10-29.72). The lowest PASI75 response was associated with adalimumab, and the lowest PASI90 response was associated with etanercept. The highest PASI75 responses were associated with ustekinumab 0.375 mg/kg (RR, 7.25) and 0.75 mg/kg (RR, 7.45), while the highest PASI90 response was associated with ixekizumab (RR, 14.50) and secukinumab (RR, 27.68-29.72). The pooled RR for PASI75 was 4.16 (95% CI, 3.21-5.39) and for PASI90 was 9.28 (95% CI, 5.80-14.86). Funnel plot asymmetry was significant by Egger test for PASI90 (P =.017) but not for PASI75 (P =.243), and the Begg test was not significant for either PASI score.
The pooled RR for corresponding adult studies showed higher responses to biologics than placebo, with the highest PASI75 response seen with ixekizumab (pooled RR, 16.18; 95% CI, 11.83-22.14) and secukinumab (pooled RR, 15.35; 95% CI, 12.49-18.86). Ixekizumab and secukinumab also showed the highest PASI90 treatment effects compared with placebo.
In the pediatric studies, the incidence of serious adverse events were low for patients receiving ixekizumab, ustekinumab, and etanercept. Pediatric patients receiving adalimumab saw a paradoxical effect on serious adverse events (0.4 mg/kg: 8%; 0.8 mg/kg: 0%). Serious adverse events were also low in the adult studies (up to 3%). Overall, adverse events were more frequent with etanercept and adalimumab than with ustekinumab. The most frequently reported adverse event was upper respiratory infections. In adults, overall adverse events were higher in brodalumab, ixekizumab, and secukinumab than in guselkumab, risankizumab, and tildrakizumab.
The study was limited by the small number of pediatric studies.
“Monoclonal antibodies inhibiting IL-17 signaling and newer IL-12/23 antagonists may offer even greater disease control in pediatric psoriasis with similar or fewer serious adverse events than TNF-inhibitors,” the study authors concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Golhen K, Winskill C, Theiler M, et al. Understanding efficacy-safety balance of biologics in moderate-to-severe pediatric psoriasis. Front Med (Lausanne). Published online September 26, 2022. doi:10.3389/fmed.2022.944208