Novel Vitiligo Topical Therapy Improves Patient Quality of Life and Clinical Outcomes

The National Institutes of Health (NIH) and the American Academy of Dermatology (ADA) indicate that vitiligo is characterized as a chronic, autoimmune inflammatory skin condition resulting in patches of depigmented skin in degrees of severity, primarily affecting the face and hands but can occur on any part of the body.^1-3 There are two types of vitiligo: segmental (depigmented patches appear on one side of the body) and non-segmental (depigmented patches appear on both sides of the body).² The ADA indicates that non-segmental vitiligo is the most common type of vitiligo.²

Various publications have noted that vitiligo is often correlated with a diminished quality of life, may negatively affect a patient’s well-being and self-esteem, and is often experienced by patients with other autoimmune comorbid conditions (ie, alopecia areata, thyroid disease, diabetes mellitus, RA, IBS, atopic dermatitis, psoriasis, etc) and is associated with considerable health challenges and direct and indirect costs.^1-6 A recent study published in Cureus revealed that patients with vitiligo often experience noteworthy psychological burdens, including depression and anxiety.³

Results from a recent survey study published in JAMA Dermatology revealed that in the US, an estimated 40% of vitiligo cases in adults may be undiagnosed, and based on their findings wrote, “The current population-based prevalence estimate of overall (diagnosed and undiagnosed combined) vitiligo in adults is between 0.76% (1.9 million cases in 2020) and 1.11% (2.8 million cases in 2020).”⁴

Findings from a recent cohort analysis published in the Journal of Investigative Dermatology indicated that patients with vitiligo sustained meaningfully greater all-cause health care resource utilization and vitiligo-related costs compared to individuals without vitiligo with values reported as $15,551 versus $7,735 and $3,490 versus $54 respectively.⁶

Another recent publication in Dermatology & Therapy sought to assess the incidence and challenges of associated comorbidities among patients with vitiligo and revealed that among 13,687 patients with vitiligo and 54,748 subjects without vitiligo, those with vitiligo were more likely also to be diagnosed with other autoimmune conditions as well as sleep disturbances, anxiety, and depression.⁷

While there is no cure for vitiligo, ongoing research efforts have gained more insight into the pathogenesis of vitiligo and gaining more insight into the role of targeted therapies in the treatment of vitiligo.

In a recent publication in Dermatology &Therapy, authors conducted a real-world study to assess the types of therapies prescribed and patient usage of therapies within the first 12 months of a vitiligo diagnosis. The authors revealed that of the 19,335 patients in the study, 49.9% were not receiving any treatment during the 12-month follow-up visit. Among those receiving therapies, the most frequently used therapies were high-potency topical corticosteroids, oral corticosteroids, and topical calcineurin inhibitors.⁸ The study also revealed that many patients receiving therapies were unlikely to change or use a combination of therapies.⁸

Until recently, the standard therapy for vitiligo included the use of phototherapy, surgical procedures, and topical therapies; however, these therapies are not FDA-approved, and health experts indicate that their therapeutic effects are limited, including poor efficacy and ADRs related to long-term use, overall effects are generally suboptimal and do not address the underlying pathophysiologies of vitiligo.^9-11 Additionally, studies show that the rate of adherence to therapy with traditional topical therapies and frequent office visits for phototherapy is often low, and the efficacy of standard therapies varies from patient to patient, therefore generating poor outcomes.^3,10,11

Findings from a 2021 survey involving 325 patients with vitiligo indicated that 49% of participants reported that the standard therapies were ineffective, 50% were unsatisfied with the traditional therapies, and a large percentage reported emotional challenges associated with vitiligo.¹²

In July 2022, the FDA approved Opzelura (ruxolitinib) cream 1.5% as the only topical formulation of a selective Janus kinase (JAK1/JAK2) inhibitor approved in the US, marking the first and only FDA-approved treatment for repigmentation in adults and pediatric patients 12 years and older for the treatment of nonsegmental vitiligo.13 In September 2021, this agent was also approved as a short-term and non-continuous chronic topical treatment of mild to moderate atopic dermatitis (AD) for individuals 12 years of age and older who are not immunocompromised and whose disease is not satisfactorily controlled with topical prescription therapies, or when those therapies are not recommended.¹³

The FDA approval for the treatment of vitiligo was established on clinical data from the critical Phase 3 TRuE-V clinical trial program (TRuE-V1 and TRuE-V2), assessing the safety and efficacy of Opzelura versus vehicle in more than 600 individuals diagnosed with nonsegmental vitiligo, age 12 and older. In both trials, participants with nonsegmental vitiligo were randomized to receive therapy with topical Opzelura cream or placebo cream applied to the affected area twice daily for 24 weeks, followed by an additional 28 weeks of treatment with Opzelura for all subjects. Results revealed that at the end of the 24-week treatment period, 30% of Opzelura patients noted at least 75% improvement in the facial Vitiligo Area Scoring Index, compared with 10% of placebo patients.¹³ The novel topical cream is intended to be applied twice a day to affected areas of up to 10% of the body’s surface area, and in clinical trials, the most frequently reported ADRs included application site acne, application site pruritus, nasopharyngitis, headache, urinary tract infection, application site erythema, and pyrexia.¹⁴ The prescribing information for Opzelura also contains a Boxed Warning regarding serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis.14 In October 2023, long-term data from the Phase 3 TRuE-V Program was presented at the European Academy of Dermatology and Venereology (EADV) Congress 2023, which indicated that patients who initially experienced limited or no facial or total body repigmentation at 6 months attained enhanced repigmentation after continuous usage of Opzelura for up to 2 years.¹⁵

Other potential therapies, including oral therapies such as an investigational oral JAK1 inhibitor, povorcitinib, are currently under investigation in clinical trials. On October 11, 2023, the 52-week data from a Phase 2b clinical trial was presented at the EADV Congress 2023 and revealed that longer-term use of this agent generated further improvement in total body and facial repigmentation in adults with extensive nonsegmental vitiligo.¹⁶ More information can be found at https://clinicaltrials.gov/study/NCT04818346.

Conclusion

Vitiligo is more than just a cosmetic condition and is associated with significant health burdens, other chronic comorbidities, and direct and indirect economic burdens. The data available for the first and only FDA-approved therapy is promising. Its use in appropriate candidates has the potential to improve clinical outcomes and lessen the challenges and burdens associated with vitiligo.

Due to their frequent interactions with patients, pharmacists can be instrumental in the care of patients with vitiligo by providing information about vitiligo, directing patients to support resources, including cost savings programs, the pros and cons of available therapies, the proper use of recommended therapies, current ADA recommendations for skin care, and non-pharmacological measures that may be beneficial such as avoiding stress, using sunscreen, and the importance of routine health care. Pharmacists can also be instrumental in identifying ideal candidates for novel therapies such as Opzelura and by making clinical recommendations tailored to patient needs, screening for possible drug/drug interactions and contraindications, routine monitoring of patient’s response to therapy, and by reminding patients about the value of adherence to therapy to improve clinical outcomes.

References

1. Garrick NDD. Vitiligo: Diagnosis, treatment, and steps to take. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Published April 12, 2017. Accessed October 19, 2023. https://www.niams.nih.gov/health-topics/vitiligo/diagnosis-treatment-and-steps-to-take
2. Ludmann P. Vitiligo: Who gets and causes. www.aad.org. Published June 29, 2022. Accessed October 19, 2023. https://www.aad.org/public/diseases/a-z/vitiligo-causes
3. Salama AH, Alnemr L, Khan AR, et al. Unveiling the unseen struggles: A comprehensive review of vitiligo’s psychological, social, and quality of life impacts. Cureus. 2023;15(9). doi:10.7759/cureus.45030
4. Gandhi K, Ezzedine K, Anastassopoulos KP, et al. Prevalence of vitiligo among adults in the United States. JAMA Dermatology. 2022;158(1):43-50. doi:10.1001/jamadermatol.2021.4724
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6. Ezzedine K, Ahmed, Li C, Camp HS, Pandya AG. Economic burden among patients with vitiligo in the United States: A retrospective database claims study. Journal of Investigative Dermatology. Published online September 1, 2023. doi:https://doi.org/10.1016/j.jid.2023.08.025
7. Ezzedine K, Ahmed, Li C, Camp HS, Pandya AG. Comorbidity burden among patients with vitiligo in the United States: A large-scale retrospective claims database analysis. Dermatology and Therapy. 2023;13(10):2265-2277. doi:10.1007/s13555-023-01001-2
8. Rosmarin D, Soliman AM, Li C. Real-world treatment patterns in patients with vitiligo in the United States. Dermatology and Therapy. 2023;13(9):2079-2091. doi:10.1007/s13555-023-00983-3
9. Feng Y, Lu Y. Advances in vitiligo: Update on therapeutic targets. Frontiers in Immunology. 2022;13. doi:10.3389/fimmu.2022.986918
10. Ezzedine K, Eleftheriadou V, Whitton M, Nanja van Geel. Vitiligo. The Lancet. 2015;386(9988):74-84. doi:10.1016/S0140-6736(14)60763-7
11. Karagaiah P, Valle Y, Sigova J, et al. Emerging drugs for the treatment of vitiligo. Expert Opinion on Emerging Drugs. 2020;25(1):7-24. doi:10.1080/14728214.2020.1712358.
12. Narayan VS, Uitentuis SE, Luiten RM, Bekkenk MW, Wolkerstorfer A. Patients’ perspective on current treatments and demand for novel treatments in vitiligo. Journal of the European Academy of Dermatology and Venereology. 2020;35(3):744-748. doi:10.1111/jdv.16927
13. Research C for DE and. FDA approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older. FDA. Published online July 19, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older
14. Opzelura Prescribing Information. Wilmington, DE: Incyte Corporation; 2022.
15. New Long-Term Data from Incyte Phase 3 TRuE-V Program Demonstrates Efficacy of Continued Treatment with Opzelura^® (ruxolitinib) Cream in Nonsegmental Vitiligo Patients | Incyte. Incyte. Published 2023. Accessed October 19, 2023. https://investor.incyte.com/news-releases/news-release-details/new-long-term-data-incyte-phase-3-true-v-program-demonstrates
16. 16. Incyte Announces Positive 52-Week Data from Phase 2b Study Evaluating Povorcitinib (INCB54707) in Patients with Extensive Nonsegmental Vitiligo. BioSpace. Accessed October 19, 2023. https://www.biospace.com/article/releases/incyte-announces-positive-52-week-data-from-phase-2b-study-evaluating-povorcitinib-incb54707-in-patients-with-extensive-nonsegmental-vitiligo/