A study comparing the efficacy of topical 2% Tofacitinib and 0.05% Fluticasone propionate in children and adolescents aged 2-18 years with mild to moderate atopic dermatitis.

Atopic Dermatitis (AD) is a common inflammatory skin condition affecting almost 20-30% of children and 2-10% of adults. The pathogenesis of AD is multifactorial and for the ease of understanding, it can be considered as an interplay between-1) epidermal barrier dysfunction; 2) immune dysregulation and 3) altered cutaneous microbiome. Further alterations by environmental as well as genetic factors lead to heterogeneity of pathophysiological mechanisms.

Inspite of the complex, multifactorial and evolving pathophysiology of AD, it is being treated with a uniform approach. Management of AD involves patient/parent education along with skin care and emollient use coupled with topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) as the first line agents to control flares of mild-moderate AD. Phototherapy and systemic agents like mycophenolate mofetil, methotrexate, cyclosporine and corticosteroids are used in patients with moderate-severe AD with sub-optimal response to topical treatment. However, topical corticosteroids carry several side effects like skin atrophy, striae, telangiectasia, rosacea ,perioral dermatitis when used on face etc. There are studies showing long term safety of TCIs in paediatric population with AD. However, they carry a “black box” warning of lymphomas. Hence additional topical treatment options are needed. A plethora of new targeted therapies-both oral and topical, have emerged recently.

The JAK/STAT pathway is implicated in the pathogenic mechanism of AD, as shown by several studies. The JAK signal transducer and STAT transcription pathway are involved in majority of inflammatory cytokines in AD, including Th2 cytokines IL-4 and IL-13 which result in downstream intracellular signal transduction. Additionally, regulatory T cells (Tregs) in the skin are depleted in AD. Differentiation and proliferation of Tregs depends on transcription factor Foxp3 which is found to be controlled by JAK/STAT signalling. There have been a few trials assessing the efficacy of topical JAK inhibitor formulations in AD. Tofacitinib is a small molecule selectively inhibiting JAK1 and JAK3. Bissonnette et al (2016) evaluated 2% Tofacitinib ointment in 69 adult patients with mild-moderate AD in a double-blind phase 2 study. They observed “81.7% improvement in Eczema Area and Severity Index (EASI)” in topical Tofacitinib vs “29.9 % in vehicle at week 4.” Moreover, Tofacitinib also demonstrated improvement in the severity of itching with from day 1 of initiation of the treatment. Tofacitinib is being used commonly in AD and the topical preparation has been approved by the DCGI in treatment of mild to moderate AD.

Most of the trials assessing new targeted therapies like JAK inhibitors for AD are vehicle-controlled studies. A major loophole is the lack of data in the paediatric age group even though paediatric population bears the maximum brunt of the disease.  Dermatologists are faced with a challenge while instituting such drugs in regular practice as there are lack of comparative studies to guide decisions regarding the same.

Through this study, we shall compare the efficacy of 2% topical Tofacitinib with 0.05% Fluticasone propionate in patients aged 2-18 years of mild-moderate Atopic Dermatitis. The study design will be a prospective randomized controlled study where patients of mild-moderate atopic dermatitis aged 2-18 years will be randomly allocated into two parallel comparison groups. One group will be prescribed 2% Tofacitinib and the other group will be prescribed 0.05% Fluticasone propionate. Follow up will be done for 6 weeks to assess the improvement in clinical symptoms. Percentage of people achieving 75% reduction or more from their baseline SCORAD values will be assessed alongside other secondary endpoint parameters. The levels of serum Thymus and Activation Regulated Chemokine (TARC) will be measured prior to and after 6 weeks to assess the effect of the topical treatment on the given biomarker and thus objectively assess the effect on the severity of the lesions. Our main rationale behind this study is to compare the efficacy of topical Tofacitinib to topical Fluticasone which is a standard treatment modality used in AD. We also aim to find out whether it can be used as an effective steroid sparing alternative in paediatric and adolescent patients of mild-moderate AD.