We present data from the Topical Ruxolitinib Evaluation in Vitiligo (TRuE-V) long-term extension (LTE) study evaluating repigmentation outcomes with continued 1.5% ruxolitinib cream treatment in patients who did not achieve near-complete facial repigmentation in TRuE-V1/TRuE-V2. Among patients in the TRuE-V1/TRuE-V2 trials who applied ruxolitinib cream from day 1, approximately 66% achieved F-VASI 75 (indicative of treatment success) at week 104, increasing from nearly 31% at week 52 (TRuE-V LTE baseline); similar repigmentation improvements were reported in patients who switched from vehicle to ruxolitinib cream after TRuE-V1/TRuE-V2 at week 24, albeit with lower overall response rates due to the shorter duration of ruxolitinib cream application. These findings indicate that continued ruxolitinib cream treatment allows further repigmentation in many patients.
BACKGROUND:Icotrokinra, a targeted oral peptide, precisely blocks the interleukin-23 receptor. In two phase 3 moderate-to-severe plaque psoriasis trials, ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), icotrokinra provided significantly higher skin clearance rates versus placebo at Week 16 and deucravacitinib at Week 16 and 24. OBJECTIVES:Report findings through Week 52 of ICONIC-ADVANCE 1&2. METHODS:ICONIC-ADVANCE 1&2 randomised (2:1:2/4:1:4) adults with moderate-to-severe plaque psoriasis (body surface area ≥10%, Psoriasis Area and Severity Index [PASI] ≥12, Investigator's Global Assessment [IGA] ≥3) to icotrokinra 200 mg, placebo (transition to icotrokinra at Week 16), or deucravacitinib 6 mg once daily (transition to icotrokinra at Week 24). Outcomes assessed through Week 52 included proportions of participants achieving IGA 0/1 (with ≥2-grade improvement from baseline), PASI 90, IGA 0, PASI 100, scalp-specific IGA (ss-IGA) 0/1, patient-reported outcomes (clinically meaningful improvement [CMI; ≥4-point reduction] in Psoriasis Symptoms and Signs Diary [PSSD] itch, PSSD symptom score 0, Dermatology Life Quality Index [DLQI] 0/1), and adverse events (AEs). RESULTS:ICONIC-ADVANCE 1&2 randomised 1505 participants (774/731). Across the studies, skin clearance rates among icotrokinra-randomised participants increased through Week 24 and were durable through Week 52, with ∼70%-75% exhibiting clear/almost clear skin (IGA 0/1, PASI 90) and ∼50% demonstrating completely clear skin (IGA 0, PASI 100) during Weeks 24-52. Among participants achieving clear/almost clear skin at Week 16, ∼85%-90% maintained response at Week 52. Response rates for ss-IGA 0/1 and patient-reported outcomes were also durable through Week 52. Participants who transitioned from placebo or deucravacitinib to icotrokinra exhibited increasing response rates that were comparable to icotrokinra-randomised participants through Week 52. The AE profile of icotrokinra was similar to placebo through Week 16 and showed lower AE rates than deucravacitinib through Week 24; no safety signals were observed through Week 52. CONCLUSIONS:Once-daily icotrokinra provided robust, durable skin clearance and symptom improvement, with no safety signals, through Week 52 in adults with moderate-to-severe plaque psoriasis. Participants transitioning from placebo or deucravacitinib to icotrokinra achieved similar increased response rates to icotrokinra-randomised participants through Week 52. Findings support icotrokinra as a systemic therapy with long-term robust disease control and a favourable safety profile.
BACKGROUND:Ruxolitinib cream (1.5%) has demonstrated efficacy and safety in patients aged ≥ 2 years with mild-to-moderate atopic dermatitis. OBJECTIVE:We aimed to further investigate the safety and efficacy of ruxolitinib cream in adolescents with atopic dermatitis in an open-label study. METHODS:Patients aged 12-17 years with atopic dermatitis, an Investigator's Global Assessment score of 2/3, and 3-20% affected body surface area applied twice-daily 1.5% ruxolitinib cream for an 8-week continuous treatment period, followed by a 44-week long-term safety period in which ruxolitinib cream was applied twice daily as needed. Safety was the primary endpoint. Secondary endpoints included plasma trough concentrations of ruxolitinib. Affected body surface area, ≥ 75% improvement from baseline in Eczema Area and Severity Index, achievement of Investigator's Global Assessment score of 0/1, and ≥ 4-point improvement from baseline in the itch Numerical Rating Scale were exploratory endpoints. RESULTS:Of 103 patients, 59.2% had a baseline Investigator's Global Assessment of 3. Mean baseline body surface area and Eczema Area and Severity Index scores were 8.9% and 6.4, respectively. Over 52 weeks, 42 patients (40.8%) had treatment-emergent adverse events, most commonly upper respiratory tract infection (10.7%) and nasopharyngitis (8.7%). Three patients (2.9%) had grade ≥ 3 treatment-emergent adverse events; all were considered unrelated to treatment by the investigator. Steady-state ruxolitinib plasma concentrations during the continuous treatment period were low (geometric mean [geometric coefficient of variation], 14.2 [169] nM), consistent with the lack of observed treatment-emergent adverse events associated with systemic Janus kinase inhibition. Clinical improvements occurred during the continuous treatment period and were maintained or improved with as-needed treatment through the long-term safety period to week 52 (mean affected body surface area, 1.3%; ≥ 75% improvement from baseline in Eczema Area and Severity Index, 87.0%; Investigator's Global Assessment 0/1, 82.6%; ≥ 4-point improvement from baseline in itch Numerical Rating Scale, 41.7%). CONCLUSIONS:Ruxolitinib cream (1.5%) was well tolerated and efficacious with long-term as-needed use in adolescents with mild-to-moderate atopic dermatitis, consistent with safety and efficacy findings reported in previous phase III studies in adolescents and adults. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov identifier, NCT05456529 (registered 13 July, 2022).
Prérequis/contexte . Objectifs Évaluer l’efficacité, la sécurité, et la pharmacocinétique de delgocitinib à partir des résultats des essais de phase 3 DELTA-1 (NCT04871711) et 2 (NCT04872101). Méthodes Analyse des données chez les adultes avec un ECM modéré à sévère, traités par delgocitinib 20mg/g en crème ou son véhicule, 2 fois/jour, pendant 16 semaines (S). Evaluation de l’efficacité par le score de fissures HECSI. Calcul des taux de répondeurs avec un score de 0 ou 0/1 (léger) et d’événements indésirables (EI). Comparaison des concentrations plasmatiques de delgocitinib (DELTA-2) avec celles d’adultes sains ayant reçu une dose orale de delgocitinib (1,5mg) lors d’un essai de phase 1 (NCT05050279) et avec les concentrations inhibitrices 50 % (CI50) obtenues après enrichissement in vitro de sang total d’adultes sains. Résultats/discussions À l’inclusion, les patients avec fissures traités par delgocitinib (n=586, score HECSI fissure moyen=4,9±2,7) présentaient une maladie plus sévère que ceux sans fissure (n=52) : score HECSI moyen 73,6 vs 43,3. De S2 à S16, comparativement au groupe véhicule, une proportion plus importante de patients du groupe delgocitinib atteignait un score HECSI de 0 (S16 : 40,8 % vs 18,3 %, p<0,001) ou de 0/1 (S16 : 55,3 % vs 29,7 %, p<0,001). Le pourcentage médian d’amélioration du score HECSI entre S2 et S16 était plus élevé chez les patients recevant delgocitinib (S16 : 72,7 % vs 33,3 %, p<0,001). Aucune différence significative en termes de sécurité n’était observée entre les groupes delgocitinib avec et sans fissures (EI : 45,6 % vs 46,2 % ; EI sévères : 2,0 % vs 5,8 %). Les concentrations plasmatiques moyennes géométriques de delgocitinib (ng/mL) chez les patients avec fissures à l’inclusion (n=284) étaient minimes et diminuaient entre S1–S4 (0,23–0,21) et S16 (0,12). Elles étaient nettement inférieures à celles observées après 1,5mg de delgocitinib par voie orale (7,22ng/mL) et à la CI50 du sang total (24ng/mL). Conclusion Delgocitinib en crème a démontré son efficacité avec un profil de sécurité comparable chez les patients avec ou sans fissures. L’exposition systémique était négligeable chez les patients avec fissures traités par delgocitinib.
