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

All India Institute of Medical Sciences, Bhubaneswar

Status and phase: Completed; Phase 4

Conditions: Bullous Pemphigoid

Treatments: Drug: Prednisolone; Drug: Dapsone; Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT05984381

AIIMS BBSR/PG Thesis/2023-24

Details and patient eligibility

About

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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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62 participants in 2 patient groups

Prednisolone and Methotrexate (Control Arm)

Active Comparator group

Description:

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Methotrexate 15 mg weekly for 16 weeks.

Treatment:

Drug: Methotrexate

Drug: Prednisolone

Prednisolone and Dapsone (Test Arm)

Experimental group

Description:

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Dapsone 100 mg/day for 16 weeks

Treatment:

Drug: Dapsone

Drug: Prednisolone