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The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Efficacy and safety of ritlecitinib (an oral JAK3/TEC family kinase inhibitor) were evaluated in patients with nonsegmental vitiligo (NSV) across Fitzpatrick skin types (FSTs). Patients with FST I‐III ('light skin'; n = 247) and FST IV‐VI ('dark skin'; n = 117) received once‐daily ritlecitinib 50 mg (with/without 4‐week loading dose), low‐dose ritlecitinib or placebo for 24 weeks. At baseline, patients with light skin displayed higher CLM‐1 and NCR1 serum levels than patients with dark skin (p < 0.05). At 24 weeks, ritlecitinib 50 mg improved the extent of depigmentation measured by percent change from baseline in facial‐vitiligo area scoring index (placebo‐adjusted mean difference [90% CI]) in patients with light (−15.2 [−24.7, −5.8]; p = 0.004) and dark (−37.4 [−50.3, −24.4]; p < 0.0001) skin, with continuous re‐pigmentation through week 48. Treatment‐emergent adverse events were similar across FSTs. At weeks 4 and 24, ritlecitinib 50 mg reduced CXCL11 serum levels (p < 0.001) in patients with light skin, whereas patients with dark skin had increased levels at week 4 (p = 0.05) and no significant change at week 24. Ritlecitinib 50 mg decreased IL‐9 and IL‐22 expression levels in dark skin compared with light skin (qPCR; p < 0.05). These differences in immune dysregulations may explain why NSV patients with dark skin respond to therapy earlier than patients with light skin. [ABSTRACT FROM AUTHOR]

Background and Aims Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, was well-tolerated and efficacious in the phase 2b VIBRATO study in participants with moderate-to-severe ulcerative colitis [UC]. The aim of this study was to identify baseline serum and microbiome markers that predict subsequent clinical efficacy and to develop noninvasive serum signatures as potential real-time noninvasive surrogates of clinical efficacy after ritlecitinib. Methods Tissue and peripheral blood proteomics, transcriptomics, and faecal metagenomics were performed on samples before and after 8 weeks of oral ritlecitinib induction therapy [20 mg, 70 mg, 200 mg, or placebo once daily, N  = 39, 41, 33, and 18, respectively]. Linear mixed models were used to identify baseline and longitudinal protein markers associated with efficacy. The combined predictivity of these proteins was evaluated using a logistic model with permuted efficacy data. Differential expression of faecal metagenomics was used to differentiate responders and nonresponders. Results Peripheral blood serum proteomics identified four baseline serum markers [LTA, CCL21, HLA-E, MEGF10] predictive of modified clinical remission [MR], endoscopic improvement [EI], histological remission [HR], and integrative score of tissue molecular improvement. In responders, 37 serum proteins significantly changed at Week 8 compared with baseline [false discovery rate of <0.05]; of these, changes in four [IL4R, TNFRSF4, SPINK4, and LAIR-1] predicted concurrent EI and HR responses. Faecal metagenomics analysis revealed baseline and treatment response signatures that correlated with EI, MR, and tissue molecular improvement. Conclusions Blood and microbiome biomarkers stratify endoscopic, histological, and tissue molecular responses to ritlecitinib, which may help guide future precision medicine approaches to UC treatment. ClinicalTrials.gov NCT02958865 [ABSTRACT FROM AUTHOR]

Introduction: There is limited epidemiologic evidence on keloids using real‐world data, especially in the United States (US) across race and ethnicity. Methods: We conducted a retrospective cohort study using Cerner Real‐World Data, between 2015 and 2021, to describe the demographic and clinical characteristics of US adults with keloids. Keloids were identified using a combination of ICD‐10 and (Systemized Nomenclature of Medicine‐Clinical Terms [SNOMED] codes). Demographics (including race and ethnicity), clinical characteristics, treatment patterns, and healthcare utilization were compared across keloid and non‐keloid populations. Results: Among 5,457 keloid patients identified in the study, the majority were female (61.8%) with a mean age of 34.2 years and of non‐Hispanic Black, Hispanic, and Asian descent (P < 0.001). Relative to non‐keloid cohorts, patients with keloids had significantly higher rates of integumentary, cardiorespiratory, general, auditory, and ocular surgeries and burns (all P < 0.05). Patients with keloids were also more likely to have comorbidities like obesity, hypertension, hyperlipidemia, and diabetes (P < 0.05) when compared to those with no keloids. A large proportion of keloids were untreated; among those treated, the most common keloid treatments were medication therapy (51.5%) and surgical excision (10.6%). Non‐Hispanic Black and Hispanic keloid patients were significantly more likely to receive medication therapy and surgical excision (P < 0.001) compared to keloid patients of other races or ethnicities. Conclusions: This study provided real‐world insights into the keloid population in the US. Our findings emphasize the high burden of keloids and its substantial impact on ethnic minorities. Given high keloid recurrence rates and limited standardized treatments for keloids, further research into keloids is crucial to the development of keloid‐specific therapeutic options. [ABSTRACT FROM AUTHOR]

PF‐06817024 is a high affinity, humanized antibody that binds interleukin‐33, a proinflammatory type 2 cytokine, and thereby has the potential to inhibit downstream type 2 inflammation. This Phase 1, randomized, placebo‐controlled study was conducted in 3 parts to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics of escalating single and limited repeat PF‐06817024 doses in healthy participants (Part 1), a single dose of PF‐06817024 in participants with chronic rhinosinusitis with nasal polyps (Part 2), and repeat doses of PF‐06817024 in participants with moderate to severe atopic dermatitis (atoptic dermatitis; Part 3). PF‐06817024 was generally well tolerated in all participant populations. Most participants experienced a treatment‐emergent adverse event (healthy participants, 78.4% and 100%; participants with chronic rhinosinusitis with nasal polyps, 90.9% and 88.9%; and participants with atoptic dermatitis, 60.0% and 62.5% in the PF‐06817024 and placebo groups, respectively). No substantial deviations from dose proportionality were observed for single intravenous doses of 10‐1000 mg, indicating linear PK in healthy participants. Mean terminal half‐life ranged from 83 to 94 days after single intravenous administration in healthy participants and was similar to that observed after administration in the studied patient populations. Incidences of antidrug antibodies in the studied populations were 10.8%, 9.1%, and 5.0% for healthy participants, participants with chronic rhinosinusitis with nasal polyps, and participants with atoptic dermatitis, respectively. In addition, dose‐dependent increases were observed in total serum interleukin‐33 levels of treated participants, indicating target engagement. Overall, the PK and safety profile of PF‐06817024 supports further investigation of the drug as a potential treatment for allergic diseases. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated. [ABSTRACT FROM AUTHOR]

This article discusses the need for a reliable clinician-reported outcome tool to assess the severity and treatment response of vitiligo, an autoimmune disease that causes skin depigmentation. The study evaluated the inter- and intra-rater reliability of the Facial Vitiligo Area Scoring Index (F-VASI) in assessing the extent and severity of vitiligo in a clinical trial. The results showed strong agreement between different raters and repeated assessments by the same rater, indicating the reliability of the F-VASI. However, the study had some limitations, and further research is needed in larger patient populations. The study was supported by Pfizer, Inc. [Extracted from the article]