To evaluate the efficacy and safety of 2 percent Crisaborole Ointment versus 0.1 percent Mometasone Furoate Cream in Vitiligo - A Comparative Study

INTRODUCTION

Vitiligo is a common autoimmune condition, mostly chronic pigmentation disorder that causes depigmentation of the skin, often due to degeneration or absence of melanocytes of involved skin and affected hair. It is clinically manifested by achromic macules often associated with leukotrichia (white hairs). Vitiligo commonly involves type 3 and 4 skin types but can occur in any skin type. . While most bilateral non-dermatomal lesions start in the second to fourth decades of life, if the disease manifests within ten years of age, it usually appears along the dermatome. Almost half of the patients develop this disease before 20 years of age. Approximately 1-2 PERCENTof the general population is affected irrespective of age, sex or ethnicity. Although vitiligo is difficult to treat various modalities for treatment are present. Various hypothesis have been put forward for the pathogenesis of this condition. One hypothesis suggests that high amounts of pro-inflammatory cytokines cause oxidative stress and inflammation, worsening melanocyte survival and increasing cytotoxicity. So we need to reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines. Twenty vitiligo patients tissue and serum samples had considerably greater PDE4 enzyme levels than those of age- and sex-matched healthy controls. PDE4-dependent pathways could therefore be crucial to the pathophysiology of vitiligo. Crisaborole is a small molecule boron-based, PDE4 inhibitor approved as a topical nonsteroidal medication by FDA. Due to this inhibition cAMP levels will increase, which will cause an increase in anti-inflammatory cytokines which will cause an increase in anti-inflammatory cytokines like IL-10, and a decrease in pro-inflammatory cytokines like IL-17, IL-4, and IL-13. Mometasone Furoate is a class IV nonfluorinated corticosteroid with high potency and safe records. It will reduce inflammatory cells, chemical mediators, and reduce secretion of cytokines such as IL-2 &TNF

STUDY OBJECTIVE

To compare effectiveness , safety and adverse effects of 2% Crisaborole versus 0.1 %Mometasone Furoate Cream in vitiligo.

STUDY DESIGN -Randomized controlled trial

NUMBER OF STUDY SIZE- Minimum Sample size required is 40

Study Methodology or Procedure

INCLUSION CRITERIA: Patients who are willing for topical corticosteroids/topical crisaborole therapy with their signed informed consent.

Percentage of body surface area affected by vitiligo < 20%.

Male and female ( both ) patients will be included of age group 10 - 60 years.

Patients who did not take any vitiligo therapy for 2 months prior to the study.

EXCLUSION CRITERIA: Cases of post inflammatory hypopigmentation. Lesions involving the mucosal area. Pregnant and lactating women. Allergy or hypersensitivity to PDE4 inhibitors or steroids. Known history of malignancy, immunodeficiency, cardiovascular diseases, impaired renal and/or liver functions. Patients with signs of skin atrophy. Patients lost to follow-up after initial visits.

METHODS AND METHODOLOGY • Patients who fulfil the inclusion criteria will be allocated to the study

• Patients will be divided randomly in 2 groups - 20 patients will be asked to use 2% crisaborole ointment on focal vitiligo patches and other 20 patients will be using 0.1% mometasone furoate ointment .

• Informed consent will be obtained from the patient in their regional language after explaining the study in detail to them

• A detailed history, which includes the patient’s personal history, past medical and surgical history, allergy history, family history, and history of current medications (topical and systemic), will be noted.

• After thorough history taking, a general physical examination will be done.

• At the time of follow-up following points will be looked at in the patients

• The patients were followed up at their first month  and then at 2,4,6,8 months.

• Patients were asked for the development of any new lesions or increase in the size of previous lesions. • Patients will also be asked if they felt any improvement/color change in the lesions. • Side effects were assessed at each follow-up.

• Photos of the lesions of every patient are taken and documented for further reference and evaluation. •

The Vitiligo Area Scoring Index (VASI) was used to assess the effectiveness of treatment. It was recorded at the baseline and at each follow-up. Vitiligo Area Severity Index (VASI) The percentage of vitiligo involvement is calculated in terms of hand units. One hand unit (which encompasses the palm plus the volar surface of all digits) is approximately equivalent to 1% of the total body surface area. The degree of pigmentation is estimated to be the nearest of one of the following percentages 100% Complete depigmentation, no pigment is present 90%- Specks of pigment present 75% depigmented area exceeds the pigmented area 50%- pigmented and depigmeted areas are equal 25%- pigmented area exceeds depigmeted area 10%- only specks of depigmentation present The VASI for each body region is determined by the product of the area of vitiligo in hand units and the extent of depigmentation within each hand unit measured patch Total body VASI = All body sites [Hand Units] × [Residual depigmentation] . Study outcome or end point.

STUDY OUTCOME OR END POINTS - 1)Though vitiligo is common in our country, it is challenging to treat despite of many medical and surgical treatments both of them having their benefits and side effects. So it is imperative to choose a drug, that can be used for the long term and should have minimal side effects.

While corticosteroids like mometasone furoate are standard for vitiligo, long-term use has side effects like skin thinning, tachyphylaxis, and post-inflammatory hypo or hyperpigmentation. PDE4 inhibitors such as crisaborole may offer a steroid-sparing alternative, but their role in vitiligo is not well studied. Studies on combined or comparative efficacy between these treatments in vitiligo are limited, representing a significant gap in the literature.

3. Exploring crisaborole’s role in vitiligo could introduce a novel mechanism of action for treatment, leveraging its anti-inflammatory properties while minimizing side effects. Comparing it with mometasone furoate ensures the study addresses a clinical standard, providing valuable insights for treatment decisions.

4. If crisaborole demonstrates comparable or superior efficacy to mometasone furoate, it could become an important addition to the treatment arsenal for vitiligo. The study could establish the basis for combination therapies or rotational treatments to mitigate steroid-related adverse effects. Findings could influence future guidelines and improve the quality of life for vitiligo patients.

Ethical Consideration

Ethical committee approval will be obtained from the Institutional Human Ethics Committee(IHEC) at Chettinad Hospital And Research Institute before starting study. Consent Informed written consent will be collected from all participants. Informed and written consent will be obtained from parents and children less than 18 years , willing to take part in study .

Data confidentiality and participant anonymity will be maintained throughout the study.

Study Duration (in Months / Years - 8 months