Advancements in Targeted Therapies for Vitiligo: Prioritizing Equity in Drug Development
Vitiligo is an autoimmune disease that causes depigmentation of the skin. It affects all skin types but can be especially disfiguring in patients with skin of color due to increased contrast of the depigmented patches compared to unaffected skin. The US Food and Drug Administration’s approval of ruxolitinib, a topical Janus kinase (JAK) inhibitor, has finally provided a treatment for vitiligo patients, but the lack of diversity among the study populations for JAK inhibitors must be addressed in future clinical trials.
Practice Points
- Vitiligo is an autoimmune disease of the skin that affects all skin types but can be particularly disfiguring in those with skin of color.
- Ruxolitinib, a topical Janus kinase (JAK) inhibitor, is the only US Food and Drug Administration–approved treatment to repigment the skin in vitiligo and has shown efficacy for individuals with all skin phototypes.
- Individuals with skin of color are underrepresented in patient cohorts for JAK inhibitor clinical trials for vitiligo, mirroring a phenomenon seen in the majority of clinical trials. Ensuring diverse participant enrollment and measuring quality-of-life metrics will strengthen future clinical trials for treatment of vitiligo and other skin diseases impacting patients with skin of color.
Efficacy Metrics Beyond Repigmentation
Disparities in quality-of-life (QOL) metrics in diseases affecting individuals with skin of color also exist. In vitiligo, the contrast between affected and unaffected skin is greater in patients with skin of color, which means that for a given VASI score, the visibility of depigmentation as well as repigmentation may be variable among patients. Additionally, there is evidence that QOL concerns vary between patients with skin of color and those with lighter skin types. Ezzedine et al14 found that QOL concerns in vitiligo patients with darker skin focused more on appearance, while concerns in vitiligo patients with lighter skin focused more on skin cancer risk. In addition to QOL differences among individuals with different skin types, there also are well-documented differences in attitudes to vitiligo among certain ethnic or cultural groups.15 For example, the Rigveda (an ancient Hindu text) indicates that individuals with vitiligo and their progeny are disqualified from marriage. Although the JAK inhibitor clinical trials for vitiligo did not appear to show differences in the degree of repigmentation among different skin types or races/ethnicities, QOL measures were not collected as a secondary end point in these studies—despite the fact that at least 1 study had documented that QOL measures were not uniform across patients when stratified by age and extent of disease.1,11,12 This same study also presented limited data suggestive of lower QOL in patients with the darkest skin phototype.1
Considerations for Future Clinical Trials
It is logical to assume that every clinical trialist in dermatology seeks equitable representation among a diverse set of races, ethnicities, and skin types, but achieving this goal remains elusive. Two recent publications16,17 outlined the challenges and examined solutions to address enrollment disparities, including several barriers to diversity among clinical trial participants: awareness of the clinical trials among minority populations; easy access to clinical trial sites; reluctance to participate because of prior experiences of discrimination, even if unrelated to clinical trials; and a lack of workforce diversity among the clinical trialist teams. To overcome these barriers, a multifaceted approach is needed that requires action at the level of the patient, provider, community, and institution. Once diverse representation is achieved, investigators should consider the need for QOL metrics as a secondary outcome in their trials, which will ensure that the intended clinical effect is matched by patient expectations across different races and ethnicities based on the potential differential impact that diseases such as vitiligo can have on patients with skin of color.
