Efficacy and safety of Cinainu in paediatric alopecia areata: an international, double-blind, randomized, placebo-controlled, phase II/III trial

Abstract Background Alopecia areata (AA) is a debilitating autoimmune-mediated disorder marked by nonscarring hair loss. It significantly impairs patients’ quality of life (QoL). Inflammation and immune dysregulation, especially involving chemokines like interleukin-8 and Janus kinase (JAK)-dependent signalling pathways, underlie AA pathogenesis. As oral JAK inhibitors are approved for severe cases only, unmet needs persist, particularly for paediatric patients and those with moderate AA. Cinainu, a topical solution containing four botanical extracts, may address these gaps due to its anti-inflammatory, anti-apoptotic and antioxidant properties. Objectives This phase II/III study evaluated the efficacy and safety of Cinainu in children and adolescents with moderate-to-severe AA. Methods The RAAINBOW study, an international, double-blind, placebo-controlled trial, involved 107 paediatric patients randomly assigned (2 : 1) to receive Cinainu or placebo for 24 weeks, followed by a 24-week untreated follow-up period. The primary analysis included 62 patients meeting predefined criteria for moderate-to-severe AA. The primary endpoint was the relative change in Severity of Alopecia Tool (SALT) score from baseline to Week 24. Secondary outcomes included responder rate (≥ 40% improvement in SALT score from baseline to Week 24), absolute SALT score changes, and QoL improvements measured by the Children’s Dermatology Life Quality Index (CDLQI) and EuroQol Visual Analogue Scale (EQ-VAS). Safety assessments included treatment-emergent adverse events. This trial is registered with EudraCT: 2016-003208-30 and ClinicalTrials.gov: NCT03240627. Results Cinainu showed significant benefits compared with placebo in relative change in SALT score from baseline to Week 24: adjusted mean difference [95% confidence interval CI)] + 26.3% (0.1–52.5); P = 0.0488, Cohen’s d = 0.52. A significantly higher proportion of Cinainu-treated patients met responder criteria at Week 24 (26.2% vs. 5.0%; P = 0.0484). Cinainu also led to significant QoL improvements at Week 24, with effect sizes of d = 0.61 in CDLQI and d = 0.69 in EQ-VAS. Benefits were sustained during the follow-up period: adjusted mean difference (95% CI) + 39.4% (13.1–65.6); P = 0.0033, Cohen’s d = 0.80, in relative change in SALT score from baseline to Week 48 and large effect sizes in CDLQI (d = 0.79). No serious adverse events were related to Cinainu, and treatment was well tolerated. Conclusions In this study, Cinainu showed efficacy, safety and sustained benefits during follow-up in children and adolescents with moderate-to-severe AA, a population with significant unmet needs.