Breakthrough Clinical Results
AbbVie announced positive topline results from two replicate Phase 3 studies evaluating upadacitinib (RINVOQ®) in adult and adolescent patients with non-segmental vitiligo (NSV). The studies met co-primary endpoints of T-VASI 50 and F-VASI 75 at week 48, demonstrating a significant reduction in de-pigmentation. Key secondary endpoints, including F-VASI 50 at week 48, also showed statistically significant differences versus placebo. The safety profile of upadacitinib was consistent with previous findings. Upadacitinib is a JAK inhibitor currently under investigation for vitiligo, with no approved systemic therapies available for re-pigmentation.
Key Highlights
- Upadacitinib (RINVOQ®) achieved co-primary endpoints of T-VASI 50 and F-VASI 75 at week 48 in two Phase 3 studies.
- Both studies met key ranked secondary endpoints, including F-VASI 50 at week 48.
- The safety profile of upadacitinib was generally consistent with that observed in approved indications.
- These Phase 3 results represent a significant milestone in AbbVie's commitment to supporting patients and expanding our immunology portfolio to deliver innovative solutions.
Incidence and Prevalence
Global Incidence and Prevalence of Vitiligo: Latest Estimates
Global Prevalence
The global prevalence of vitiligo has been consistently reported to range from 0.5% to 2% of the population worldwide according to multiple recent studies. This makes vitiligo one of the most common skin disorders with loss of pigment.
However, a more precise estimate from recent research indicates that the global lifetime prevalence of vitiligo diagnosed by a physician or dermatologist is approximately 0.36% (95% credible interval [CrI] 0.24-0.54) in the general population, representing about 28.5 million people worldwide.
Age-Specific Prevalence
There are notable differences in prevalence between age groups:
- In adults, the global prevalence is significantly higher at 0.67% (0.43-1.07), representing approximately 37.1 million adults
- In children, the global prevalence is lower at 0.24% (0.16-0.37), representing about 5.8 million children
- Worldwide prevalence in children specifically ranges from 0% to 2.16%
Regional Variations
Prevalence varies considerably by geographic region:
- Central Europe and South Asia report the highest prevalence at 0.52% in the general population
- In Shanghai, China, a 2021 community-based survey found an estimated prevalence of 0.91%, with age-adjusted prevalence of 0.67%
- In Spain, vitiligo prevalence was 0.19% in 2021
- In Puerto Rico, a specialized dermatology clinic reported a much higher estimated prevalence of 5.2%
- In Africa and the Middle East, reported prevalence ranges from 0.18% to 5.3%
- In Latin America, prevalence ranges from 0.04% to 0.57%
- In India, about 1% of the population is affected, with the prevalence rate reported to be the highest globally
Incidence Rates
Recent incidence data shows:
- In South Korea, 24.7 cases per 100,000 person-years in 2019
- In the USA, 61.0 cases per 100,000 person-years in 2017
- Individual studies show an increasing trend in incidence rates over the periods studied
- In Korea, incidence and annual prevalence increased from 2003 to 2019, with incidence peaking in summer
- Age-specific incidence in Korea showed a bimodal distribution, with the steepest increase in those under 20 years
Gender Distribution
Several studies indicate gender differences in vitiligo prevalence:
- In Spain, females were more affected than males (0.16% vs 0.13%)
- In a study of 1,400 incident patients in Spain, most were female (53.9%)
- In Puerto Rico, among 581 vitiligo patients, 60.2% were women and 39.8% were men
- In a study of 574 children with vitiligo, the gender distribution was nearly equal: 50.5% female and 49.5% male
Genetic Factors
Genetic risk factors contribute to vitiligo development, with certain risk alleles showing differential enrichment across populations, which may explain the preponderance of vitiligo in different ethnic groups.
Key Unmet Needs and Target Populations for Vitiligo
Unmet Needs in Vitiligo Management
Vitiligo, a chronic autoimmune-mediated disease affecting 0.5-2% of the world population, presents several critical unmet needs:
- Lack of effective therapies: 26.3% of healthcare professionals don't believe effective therapy exists, while 44.6% of patients have given up finding effective treatment
- Delayed diagnosis: Patients receive formal diagnosis after a mean of 2.4 years, with 44.9% reporting previous misdiagnosis
- Misinformation: 56.7% of patients were incorrectly told vitiligo cannot be treated
- No definite cure: Despite various therapeutic options, no definite cure exists and long-term persistence of repigmentation is unpredictable
- No prognostic criteria: No reliable clinical, biological, or histological markers for establishing prognosis
- Disease stability challenges: Maintaining stability remains a major challenge despite current treatment strategies
- Slow therapeutic progress: Progress in vitiligo treatment has lagged behind other skin conditions like psoriasis or eczema
- Limited evidence on new treatments: Need for reliable evidence on effectiveness and adverse events of JAK inhibitors
Target Populations for Vitiligo Therapies
Recent research focuses on several specific populations:
- Patients with nonsegmental vitiligo (the more common type)
- Patients with segmental vitiligo
- Those with refractory vitiligo resistant to conventional therapies
- Patients with concomitant autoimmune conditions
- Non-Caucasian individuals who experience worse quality of life and healthcare access
- Patients with psychological impact from vitiligo, including increased risk of depression (aOR 1.08), anxiety (aOR 1.19), and sleep disturbance (aHR 1.15)
- Ethnically diverse populations, with significant differences in lifetime incidence: Asian (3.58%), black (2.18%), mixed (2.03%), other (1.05%), and white (0.73%)
- Transplant recipients, especially those with graft-vs-host disease who have significantly higher risk (adjusted hazard ratio 24.09)
- Patients with different Fitzpatrick skin phototypes
- Young adult patients (20-39 years) who show poorer total quality of life
- Married females with higher education and shorter disease history who demonstrate greater emotional impacts
Emerging Treatment Approaches
To address these needs, several promising approaches are being investigated:
- JAK inhibitors (tofacitinib, ruxolitinib) showing promise for refractory cases
- Cellular therapies including transplantation of epidermal keratinocyte-melanocyte cells
- Acupuncture therapy demonstrating effectiveness compared to controls
- Combination therapies such as JAK inhibitors with narrowband ultraviolet B (NB-UVB) phototherapy
The VALIANT study, the first global survey on vitiligo management, emphasizes the need for earlier diagnosis and improved disease management, with treatment goals focusing on reduction of spread, repigmentation, stabilization, and persistence of repigmentation.
Drug used in other indications
Upadacitinib Clinical Trials Beyond Vitiligo
Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, is being investigated for multiple inflammatory conditions beyond vitiligo:
Rheumatoid Arthritis
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Intervention model: Double-blind, randomized controlled phase 3 trials
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SELECT-COMPARE: Patients received once-daily oral extended-release upadacitinib 15 mg, 30 mg, or placebo for 12 weeks (2:2:1:1 randomization)
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SELECT-BEYOND: Evaluated in patients with inadequate response to previous biologic DMARDs
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Japanese study: Tested in patients with inadequate response to conventional synthetic DMARDs
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Long-term extension studies up to 10 years
Ankylosing Spondylitis
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Intervention model: Multicentre, randomized, double-blind, placebo-controlled phase 2/3 study (SELECT-AXIS 1)
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1:1 randomization using interactive response technology
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Treatment: Oral upadacitinib 15 mg once daily or placebo
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Conducted at 62 sites in 20 countries
Non-radiographic Axial Spondyloarthritis (nr-axSpA)
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Intervention model: Phase 3 trial (SELECT-AXIS 2)
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1:1 randomization to upadacitinib 15 mg once daily or placebo for 52 weeks
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Patients had objective signs of inflammation on MRI or elevated C-reactive protein
Atopic Dermatitis
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Intervention models:
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Randomized, double-blind, placebo-controlled phase 3 trial (AD Up): 1:1:1 randomization to upadacitinib 15 mg, 30 mg, or placebo with topical corticosteroids
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Head-to-head, phase 3b trial (Heads Up): 1:1 randomization to oral upadacitinib 30 mg daily or subcutaneous dupilumab 300 mg biweekly
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16-week, double-blind, placebo-controlled, dose-ranging trial: 1:1:1:1 randomization to upadacitinib 7.5, 15, or 30 mg or placebo
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Phase 3, double-blind, 3-year trial (Rising Up) in Japanese patients
Crohn's Disease
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Intervention models:
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Phase 2 double-blind study (CELEST): 1:1:1:1:1:1 randomization to placebo or upadacitinib in various dosing regimens
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Phase 3 studies (U-EXCEED, U-EXCEL, U-ENDURE)
Ulcerative Colitis
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Intervention models:
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Phase 2b induction trial
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Phase 3 induction trials (U-ACHIEVE Induction and U-ACCOMPLISH)
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Maintenance trials
Psoriatic Arthritis
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Intervention model: Randomized, placebo-controlled phase 3 trials
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Evaluated upadacitinib 15 mg and 30 mg once daily
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Some trials included adalimumab 40 mg every other week as active comparator
Systemic Lupus Erythematosus
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Intervention model: 48-week, phase 2 study (SLEek)
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1:1:1:1:1 randomization to different treatment arms
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Arms included upadacitinib 30 mg daily, combination therapy with elsubrutinib, or placebo
Giant Cell Arteritis
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Intervention model: Phase 3 randomized controlled trial (currently recruiting)
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Registered on ClinicalTrials.gov (NCT03725202)
Across these trials, upadacitinib has demonstrated efficacy for multiple indications with a manageable safety profile, though some adverse events were noted.