Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid

Study Overview
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Brief Summary
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Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder most commonly affecting the older population between 60-80 years old. The characteristic feature of BP is itchy patches associated with blisters and erosions. BP significantly affects the patient's quality of life as it causes physical discomfort with itchy patches, blisters, and erosions. Several pieces of evidence from previous studies showed that the production of autoantibodies against the hemidesmosomal anchoring proteins BP180 (Bullous Pemphigoid antigen (BPAG 2)) and BP230 (BPAG 1) is the most common cause for bullous pemphigoid. Therapeutic latency, lack of efficacy in many patients, and adverse drug reactions are the primary concerns in the current bullous pemphigoid treatment paradigm, including high-dose steroid treatment. To overcome these treatment challenges, combination therapy with agents having a steroid-sparing effect like mycophenolate mofetil, cyclophosphamide, azathioprine, and Methotrexate are tested as an add-on to low-dose steroids. 8So other immunosuppressive agents with better safety profiles and more efficacy, like Dapsone and Methotrexate as an add-on to low-dose steroids, can be used. Investigator's literature search found no randomized controlled trial with Dapsone versus Methotrexate as an add-on to first-line steroid has been conducted to compare the efficacy and safety in bullous pemphigoid patients. So, a randomized controlled trial has been planned to evaluate the safety and efficacy of add-on methotrexate versus Dapsone in bullous pemphigoid patients.

Official Title
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Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid: A Randomized Controlled Trial

Conditions
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Bullous Pemphigoid

Intervention / Treatment
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* Drug: Prednisolone
* Drug: Dapsone
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥18 of either sex with the clinical diagnosis of Bullous pemphigoid. Patients with BPDAI score ≥ 20 (moderate and severe BP). Patients must have characteristic clinical features of bullous pemphigoid at the screening and baseline visits. (Urticaria, bullae, pruritis). Patients who are willing to give informed written consent. Exclusion Criteria: Patients on any steroid-sparing agents within one month of recruitment. Treatment with a systemic corticosteroid, sulfones, within the last week. Patients with Glucose 6 phosphate dehydrogenase deficiency. Decreased liver or renal function (creatinine > 2.0mg/dl, total bilirubin > 2.5 mg/dl). Severe acute infection, severe diabetes mellitus, untreated glaucoma, congenital or acquired immunodeficiency, active gastroduodenal ulcer, severe osteoporosis, severe cardiac disease (NYHA grade IV), MI in the last four weeks, severe schizophrenia or depression. Malignancies treated by cytotoxic or immunosuppressive medications. Anaemia (Hb <9 gm/dl), leucopenia (< 3 ×10 9 cells /L) or thrombocytopenia (< 100 × 10 9 cells/ L), and H/O porphyria. Patient with a history of hypersensitivity to Methotrexate or Dapsone. Vaccination in the last two weeks. Patients with HIV, Hepatitis B, and C infection. Pregnancy and lactation, women of childbearing age without effective contraception.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, add-on, active-controlled, open-label, parallel-design clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prednisolone and Methotrexate (Control Arm)<br>prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Methotrexate 15 mg weekly for 16 weeks. | Drug: Prednisolone<br>* prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally<br>Drug: Methotrexate<br>* Methotrexate 15 mg weekly<br>|
| Experimental: Prednisolone and Dapsone (Test Arm)<br>prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Dapsone 100 mg/day for 16 weeks | Drug: Prednisolone<br>* prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally<br>Drug: Dapsone<br>* Dapsone 100 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in BPDAI (Bullous Pemphigoid Disease Area Index) score | change in BPDAI (Bullous Pemphigoid Disease Area Index) score after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone Score range from 0-360 (Minimum 0 and maximum 360) higher scores indicating greater disease activity | 8 weeks and 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in serum BP180 | change in serum BP180 after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone | 16 weeks | 
| the remission rate | remission is defined as complete subsidence of all lesions without prednisolone or minimal prednisolone dose of 10 mg or less | 8 weeks and 16 weeks | 
| the cumulative prednisolone dose | cumulative prednisolone dose after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone | 16 weeks | 
| time to the initial flare | time to the initial flare after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone | 16 weeks | 
| number of flares in study groups | number of flares in study groups after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone | 16 weeks | 
| change in the Dermatological life quality index (DLQI) | change in the Dermatological life quality index (DLQI) after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone maximum of 30 and a minimum of 0 The higher the score, the more quality of life is impaired. | 8 weeks and 16 weeks | 
| treatment-emergent adverse events | treatment-emergent adverse events in both the groups | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bullous pemphigoid, Methotrexate, Dapsone, BP180, Blister, Erosions