Comparative study of effectiveness and safety of oral azathioprine versus oral tofacitinib in the treatment of severe atopic dermatitis: a randomised controlled trial

Atopic dermatitis is a chronic inflammatory condition characterised by inherent barrier defect. It affects millions worldwide, with significant impacts on quality of life. There is a rise in the trend of atopic dermatitis in developed countries. The prevalence of atopic dermatitis in developed countries ranges from around 1 percent to around 9 percent.

It is expected that incidence and severity of atopic dermatitis will increase in the 21st century in India.

Management of atopic dermatitis mainly involves relieving symptoms, restoring skin barrier function, and preventing flares. Corticosteroids and Emollients form the cornerstone of treatment, reducing inflammation and providing hydration respectively. Topical calcineurin inhibitors are better suited for sensitive areas of the body. In moderate to severe cases, systemic immunomodulators such as cyclosporine, methotrexate, or dupilumab are reliable options.

Azathioprine is known to be effective in Atopic Dermatitis as a steroid sparing agent by its action as a purine synthesis inhibitor. It was compared with methotrexate in a previous study where both treatments achieved clinically relevant improvement and were safe in the short term.

Tofacitinib is a new molecule which acts as a JAK 1 3 inhibitor, interfering with the JAK STAT signaling pathway. Tofacitinib ointment was found to be efficacious in a  phase 2 RCT

Recently Oral tofacitinib has shown good efficacy in a case report.

To the best of our knowledge, there are no published studies comparing the efficacy of Azathioprine and Tofacitinib in severe Atopic Dermatitis.

Justification for tofacitinib use in atopy

JAK inhibitors are shown to be effective in the treatment of Atopic dermatitis.

It’s relatively a new drug and needs better statistical analysis to find the efficacy and safety profile.

It has not been compared to other drugs already established in Atopic Dermatitis treatment.

  |Study Design Randomised controlled trial single blind, after obtaining ethical approval from the Institutional ethical committee and obtaining an informed consent from patients.

  Study Setting The study will be conducted in the Department of Dermatology and Venerology, AIIMS, Bhubaneswar, from July 2024 to November 2025.

 Study Groups The study will include patients with Severe Atopic Dermatitis attending the Outpatient Department  of the Department of Dermatology and Venereology.

Treatment Group 1 Oral Prednisolone and Oral Azathioprine

Treatment Group 2 Oral Prednisolone and Oral Tofacitinib

 Sample size 29 in each group

 Inclusion criteria

1      Severe Atopic dermatitis  SCORAD score more than 49

2      Both gender

3      Age above 18 years

 Exclusion criteria

1      Doubtful cases

2      Secondary infections

3      Patients who have received steroid sparing agent in the last 6 months

4      Patients who will deny giving consent to the study

5      Patients with a history of hypersensitivity to Azathioprine or Tofacitinib

6      Pregnancy or Lactation

7      Patients with known immunosuppression or on immunosuppressive therapy

8      Patients on therapy that interacts with interventional drugs

9      Age above 65 years

10      Age below 18 years

11   Tuberculosis Patients

12    Uncontrolled Hypertension

13   Uncontrolled Diabetes Mellitus

14  Cytopenia

  Details of control NA

Details of intervention

Group 1 The patients will receive Azathioprine 50mg twice daily, which will be continued till the last follow up of 12 weeks

Group 2 The patients will receive Tofacitinib 5mg twice daily, which will be continued till the last follow-up of 12 weeks.

Patient safety

Duration of study 2 years

Outcome

Primary Outcome

1      To compare the effectiveness of both the drugs by measuring the mean relative reduction in the EASI scoring of atopic dermatitis, pruritus over a visual analog scale

 Secondary Outcome

1     To assess the safety profile of Azathioprine and Tofacitinib by assessing the number and severity of adverse events at each visit.

 2      To compare the effectiveness of both the drugs by measuring the mean relative reduction in the Modified EASI score, SCORAD, Objective SCORAD. In each group

 3     Proportion of patients achieving 75 percent improvement in EASI score from baseline in each group.

 4    Number and severity of recurrences after 12 weeks.

 5      Total cumulative dose of steroids required during 12 weeks and after 12 weeks.