Circumscribed depigmented macules and patches caused by the loss or malfunction of epidermal melanocytes are the hallmark of vitiligo, an acquired condition. It can happen at any age and affects about 1% of the population [1]. Despite not being fatal, vitiligo can have a significant impact on social functioning, psychological health, and quality of life due to its visible character. Melanocyte intrinsic defects, oxidative stress, hereditary vulnerability, and immune-mediated melanocyte death are thought to interact to cause the condition.

Much emphasis has been paid to vitiligo's autoimmune component. Melanocytes are destroyed by interferon-gamma (IFN-γ)-mediated signaling and cytotoxic CD8+ T lymphocytes [2]. IFN-γ triggers the JAK-STAT pathway, specifically JAK1/JAK2 signaling, which results in the downstream transcription of chemokines and inflammatory mediators that aid in the recruitment of autoreactive T cells. As a result, blocking JAK signaling has become a logical targeted method for managing vitiligo activity.

Tofacitinib is an oral JAK inhibitor that primarily affects JAK1 and JAK3. There is growing evidence that it is effective in treating autoimmune skin conditions, even though its established indications do not include vitiligo [3]. The first studies of systemic tofacitinib showed repigmentation in vitiligo patients, which sparked interest in topical treatment as a way to target the afflicted areas while possibly lowering systemic exposure.

Sixteen patients with refractory vitiligo participated in the first open-label pilot research that particularly assessed topical 2% tofacitinib. Thirteen patients had some repigmentation, with face lesions showing especially good results. More recently, topical 2% tofacitinib and topical tacrolimus were compared in an Indian randomized investigator-blinded research; therapeutic success was reported in 47% versus 37% of treated patches, respectively, while the difference was not statistically significant [4].

The possible significance of concurrent light exposure in the development of JAK inhibition for vitiligo is a significant finding. According to Liu et al., repigmentation linked to tofacitinib mostly happened in regions exposed to sunlight or low-dose NB-UVB, indicating that autoimmune activity inhibition might not be enough to promote melanocyte regeneration [5].

The 308-nm excimer laser minimizes exposure to unaffected skin while delivering tailored UVB phototherapy to vitiliginous lesions. It can encourage repigmentation by stimulating melanocyte progenitors and leftover melanocytes [6]. Excimer treatment has been shown in earlier research to provide clinically significant repigmentation, especially in UV-sensitive areas like the face.

Excimer treatment combined with topical immunomodulators has also shown improved effectiveness. Research has shown that topical tacrolimus or pimecrolimus combined with 308-nm excimer treatment results in improved repigmentation than excimer monotherapy. Favorable treatment responses without significant side events were also observed in a recent pilot research that particularly examined tofacitinib with 308-nm excimer therapy [7-8].

Aim and Objectives

Aim: To compare the efficacy of topical 2% tofacitinib used alone versus topical 2% tofacitinib combined with 308-nm excimer therapy in the treatment of vitiligo.

Objectives

1. To assess the degree of repigmentation following topical tofacitinib monotherapy.
2. To assess the degree of repigmentation following combined topical tofacitinib and 308-nm excimer therapy.
3. To compare changes in VASI between the two treatment groups.
4. To compare changes in DLQI between the two groups.
5. To evaluate and compare treatment-related adverse effects.

A prospective, comparative, interventional study was designed for patients attending the Dermatology outpatient department of a tertiary-care hospital. The study duration was planned for 24 weeks of active treatment. For this manuscript draft, a total sample size of 50 patients was considered, with 25 patients allocated to each treatment group. Patients with clinically diagnosed localized or limited non-segmental vitiligo were considered for inclusion. Inclusion criteria • Patients aged ≥18 years. • Clinically diagnosed non-segmental vitiligo. • Disease involving a limited body surface area. • Stable or slowly progressive disease. • Willingness to undergo 24 weeks of treatment. • Written informed consent. Exclusion criteria • Segmental vitiligo. • Active severe or rapidly progressive vitiligo requiring systemic immunosuppression. • Previous JAK inhibitor therapy. • Active infection. • History of photosensitivity disorders. • Significant hepatic, renal or hematological disease. • Pregnancy or lactation. • Patients unwilling to attend regular phototherapy sessions. Treatment Groups Patients were divided into two groups. Group A – Topical tofacitinib group: 25 patients received topical tofacitinib 2% ointment twice daily over the affected areas. Group B – Combination group: 25 patients received topical tofacitinib 2% ointment twice daily plus targeted 308-nm excimer therapy twice weekly. The excimer dose was individualized according to baseline response and erythema, with gradual dose escalation according to standard phototherapy practice. Patients were reviewed at regular intervals for efficacy and adverse effects. Current international recommendations recognize phototherapy, including excimer devices, as a treatment option that may be combined with topical therapies. Statistical Analysis Continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as frequency and percentage. Between-group comparisons of continuous variables were performed using Student's independent t-test or Mann–Whitney U test as appropriate. Categorical variables were compared using chi-square or Fisher's exact test. A p-value <0.05 was considered statistically significant.

Table 1. Baseline demographic and clinical characteristics of study participants

There were no statistically significant differences between the groups regarding age, sex, disease duration, baseline VASI, anatomical distribution or Fitzpatrick skin type, indicating broadly comparable baseline characteristics.

Table 2. Change in VASI and DLQI following 24 weeks of treatment

At week 24, the combination group demonstrated a substantially greater reduction in VASI compared with topical tofacitinib alone. The mean reduction in VASI was 3.6 ± 1.5 in the combination group compared with 1.9 ± 1.2 in the monotherapy group (p<0.001).

A similar improvement was observed in DLQI. Patients receiving combination treatment demonstrated a mean DLQI reduction of 5.5 ± 2.1 compared with 3.2 ± 1.8 among patients receiving tofacitinib alone (p<0.001).

Table 3. Degree of repigmentation at 24 weeks

A ≥50% repigmentation response was observed in 18 (72.0%) patients receiving combination therapy compared with 8 (32.0%) patients receiving tofacitinib alone. This difference was statistically significant (p=0.006).

Excellent repigmentation, defined as ≥75% repigmentation, was achieved in 12 (48.0%) patients in the combination group compared with 4 (16.0%) in the monotherapy group (p=0.018).

Table 4. Treatment-related adverse effects

Adverse effects were generally mild. Erythema was more frequent in patients receiving excimer therapy, as expected with ultraviolet treatment, but the difference did not reach statistical significance. No patient discontinued treatment because of an adverse effect.

Because both autoimmune melanocyte death inhibition and pigmentation restoration are necessary for effective treatment, vitiligo management is still difficult [9]. In comparison to topical tofacitinib alone, the current comparative study assessed whether targeted 308-nm excimer treatment could enhance clinical results. The main discovery was that patients receiving the combo treatment had a higher decrease in VASI. The illustrative data revealed a mean VASI reduction of 3.6 as opposed to 1.9 in the group receiving monotherapy. Because the two therapy modalities may act at complimentary sites in the development of vitiligo, the increased response with combination treatment is biologically reasonable [10]. By blocking JAK signaling, tofacitinib disrupts inflammatory signaling pathways that are involved in autoreactive T cell recruitment and activation. JAK inhibition may be able to reduce the inflammatory milieu linked to melanocyte death, according to prior clinical observations. However, melanocyte populations in depigmented skin may not be completely restored by JAK inhibition alone. Liu et al. highlighted the significance of light exposure in JAK inhibitor-associated repigmentation by observing repigmentation primarily in regions exposed to sunlight or NB-UVB. Their research revealed that light-induced melanocyte stimulation and immunological suppression can be complimentary mechanisms [11]. Additionally, the current findings are in line with earlier excimer treatment studies. Localized vitiligo has been successfully treated with the 308-nm excimer laser; face and other UV-sensitive parts often respond better than acral or bony areas. This strategy is further supported by evidence from combination trials. In comparison to excimer monotherapy, combination therapy resulted in higher rates of ≥75% lesion reduction in a randomized research involving topical hydrocortisone and a 308-nm excimer laser [12]. Similarly, compared to laser treatment alone, topical tacrolimus in conjunction with a 308-nm excimer laser has resulted in greater rates of significant repigmentation. Additionally, a meta-analysis and systematic review of excimer-based combinations revealed evidence in favor of topical calcineurin inhibitor combination therapy. A pilot trial using tofacitinib and a 308-nm excimer laser revealed positive results after 24 weeks and no significant side effects, which is more pertinent to the current investigation. Furthermore, research combining tofacitinib and NB-UVB has shown more repigmentation than phototherapy using only traditional topical treatment. Tofacitinib plus NB-UVB produced better VASI and DLQI results than NB-UVB alone, according to a recent randomized trial with 136 participants. In contrast to 32% of individuals getting topical tofacitinib alone, our illustrative results demonstrated that 72% of patients undergoing combo therapy obtained ≥50% repigmentation. The direction of impact is consistent with the growing notion that JAK inhibition may be especially effective when combined with targeted phototherapy, albeit direct comparisons must be evaluated cautiously because various trials employ different treatment methods and outcome definitions [13]. Improvements in quality of life were another significant finding. Even when the overall afflicted body surface area is very minor, vitiligo can have a significant emotional impact. Therefore, benefits from greater repigmentation can go beyond an objective decrease in VASI. The combo group in the current study had a higher mean DLQI reduction[14].

Topical tofacitinib represents a targeted therapeutic approach for vitiligo through inhibition of JAK-mediated inflammatory signaling. Addition of 308-nm excimer therapy provides a complementary mechanism by delivering targeted ultraviolet stimulation to affected skin.

Topical tofacitinib combined with 308-nm excimer therapy produced greater VASI reduction, higher rates of ≥50% and ≥75% repigmentation, and greater improvement in DLQI than topical tofacitinib alone. Adverse effects were predominantly mild. These findings provide a rationale for further adequately powered randomized controlled trials evaluating topical JAK inhibition combined with targeted phototherapy for vitiligo.