INTRODUCTION
Vitiligo is a chronic autoimmune skin disorder characterized by progressive loss of epidermal melanocytes, resulting in depigmented macules and patches.1 The visible nature of vitiligo can impose a substantial psychosocial burden, including diminished quality of life, reduced self-esteem, and impaired social functioning.2,3 Psychiatric comorbidities, particularly depression and anxiety, occur at disproportionately high rates in this population and are frequently attributed to the visible and often stigmatizing nature of the disease.4 Lesions commonly appear on cosmetically sensitive and visible areas, such as the face and hands, amplifying social scrutiny and emotional distress.3,5
Recent therapeutic advances have introduced topical Janus kinase (JAK) inhibitors, including ruxolitinib 1.5% cream, as targeted treatments for repigmentation in vitiligo.6 Ruxolitinib inhibits JAK1 and JAK2 signaling pathways implicated in autoimmune melanocyte destruction, and phase three clinical trials have demonstrated meaningful clinical repigmentation with favorable tolerability profiles.6,7 Despite the recognized psychiatric burden of vitiligo, limited evidence exists regarding whether effective treatments such as topical ruxolitinib confer measurable benefits in reducing incident psychiatric comorbidities. The present study leverages large-scale, real-world data to examine the association between topical ruxolitinib use and psychiatric disorders among adults with vitiligo.
Recent therapeutic advances have introduced topical Janus kinase (JAK) inhibitors, including ruxolitinib 1.5% cream, as targeted treatments for repigmentation in vitiligo.6 Ruxolitinib inhibits JAK1 and JAK2 signaling pathways implicated in autoimmune melanocyte destruction, and phase three clinical trials have demonstrated meaningful clinical repigmentation with favorable tolerability profiles.6,7 Despite the recognized psychiatric burden of vitiligo, limited evidence exists regarding whether effective treatments such as topical ruxolitinib confer measurable benefits in reducing incident psychiatric comorbidities. The present study leverages large-scale, real-world data to examine the association between topical ruxolitinib use and psychiatric disorders among adults with vitiligo.
MATERIALS AND METHODS
We performed a retrospective, propensity score–matched cohort analysis on TriNetX comparing adult patients with vitiligo treated with topical ruxolitinib to matched controls without ruxolitinib exposure. Adults with vitiligo were identified using the International Classification of Diseases (ICD-10) code L80 and matched 1:1 on age, sex, race, and ethnicity, resulting in two balanced cohorts of 4,936 patients each. Treatment status was determined from prescription records for ruxolitinib (RxNorm 1193326). Since no code distinguishes topical from oral formulations, prescriptions were restricted to those originating in dermatologic outpatient settings, and patients with hematologic or myeloproliferative diseases, typically treated with oral ruxolitinib (ICD-10 D47.4, D45, D89.810, D89.813, D76.1, D47.1, C94.3) were excluded.
Psychiatric and behavioral outcomes were identified using valid ICD-10 codes, while procedural and mental health service utilization outcomes were captured via Current Procedural Terminology (CPT) codes. Incidence rates were compared between groups using relative risk (RRs) with 95% confidence intervals (CIs) calculated using Wald’s method. Statistical significance was determined by two-tailed P-values, with significance defined as P<0.05. The observation period for outcomes started one day after the index date, which was defined as the first topical ruxolitinib prescription date for treated patients or a matched index date for controls, and extended through available follow-up.
Psychiatric and behavioral outcomes were identified using valid ICD-10 codes, while procedural and mental health service utilization outcomes were captured via Current Procedural Terminology (CPT) codes. Incidence rates were compared between groups using relative risk (RRs) with 95% confidence intervals (CIs) calculated using Wald’s method. Statistical significance was determined by two-tailed P-values, with significance defined as P<0.05. The observation period for outcomes started one day after the index date, which was defined as the first topical ruxolitinib prescription date for treated patients or a matched index date for controls, and extended through available follow-up.
RESULTS
Patients treated with topical ruxolitinib exhibited significantly lower rates of multiple psychiatric comorbidities and mental health service utilization compared to untreated controls (Table 1). Depressive episodes occurred in 1.9% of the treated group versus 7.2% in controls (RR 0.26; CI 0.21-0.33). Recurrent major depressive disorder was similarly reduced (0.9% vs 3.3%; RR 0.27; CI 0.19-0.37). Significant risk reductions were also observed for phobic anxiety disorders (RR 0.43; CI 0.24-0.79), other anxiety disorders (RR 0.33; CI 0.28-0.39), persistent mood disorders (RR 0.297; CI 0.16-0.54), and unspecified mood disorders (RR 0.37; CI 0.22-0.62). Sleep disorders unrelated to substances or known physiological conditions were also reduced (0.73% vs 2.67%; RR 0.28; CI 0.19-0.40). Additionally, mental and behavioral disorders due to psychoactive substance use were less common in treated patients (1.09% vs 4.80%; RR 0.22; CI 0.17-0.30).
The association with obsessive-compulsive disorder did not achieve statistical significance (RR 0.53; CI 0.25-1.13). Although the point estimates for bipolar disorder (RR 0.23; CI 0.12-0.46)
The association with obsessive-compulsive disorder did not achieve statistical significance (RR 0.53; CI 0.25-1.13). Although the point estimates for bipolar disorder (RR 0.23; CI 0.12-0.46)
