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

NCT05984381 | Completed Phase 4

• 1 other identifier: AIIMS BBSR/PG Thesis/2023-24
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bullous Pemphigoid

Keywords

Bullous pemphigoid; Methotrexate; Dapsone; BP180; Blister; Erosions

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• change in serum BP180

  16 weeks

• the remission rate

  8 weeks and 16 weeks

• the cumulative prednisolone dose

  16 weeks

• time to the initial flare

  16 weeks

• number of flares in study groups

  16 weeks

Study Arms (2)

Prednisolone and Methotrexate (Control Arm)

ACTIVE COMPARATOR

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

Drug: Prednisolone; Drug: Methotrexate

Prednisolone and Dapsone (Test Arm)

EXPERIMENTAL

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

Drug: Prednisolone; Drug: Dapsone

Interventions

Prednisolone DRUG

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally

Prednisolone and Dapsone (Test Arm); Prednisolone and Methotrexate (Control Arm)

Dapsone DRUG

Dapsone 100 mg/day

Prednisolone and Dapsone (Test Arm)

Methotrexate DRUG

Methotrexate 15 mg weekly

Prednisolone and Methotrexate (Control Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

AIIMS Bhubaneswar

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (8)

• Lu L, Chen L, Xu Y, Liu A. Global incidence and prevalence of bullous pemphigoid: A systematic review and meta-analysis. J Cosmet Dermatol. 2022 Oct;21(10):4818-4835. doi: 10.1111/jocd.14797. Epub 2022 Feb 1.

  PMID: 35080093 BACKGROUND

• Chen X, Zhang Y, Luo Z, Wu Y, Niu T, Zheng J, Xie Y. Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis. PLoS One. 2022 Apr 15;17(4):e0264705. doi: 10.1371/journal.pone.0264705. eCollection 2022.

  PMID: 35427358 BACKGROUND

• Genovese G, Di Zenzo G, Cozzani E, Berti E, Cugno M, Marzano AV. New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update. Front Immunol. 2019 Jul 2;10:1506. doi: 10.3389/fimmu.2019.01506. eCollection 2019.

  PMID: 31312206 BACKGROUND

• Patton T, Korman N. Role of methotrexate in the treatment of bullous pemphigoid in the elderly. Drugs Aging. 2008;25(8):623-9. doi: 10.2165/00002512-200825080-00001.

  PMID: 18665656 BACKGROUND

• Tirado-Sanchez A, Diaz-Molina V, Ponce-Olivera RM. Efficacy and safety of azathioprine and dapsone as an adjuvant in the treatment of bullous pemphigoid. Allergol Immunopathol (Madr). 2012 May-Jun;40(3):152-5. doi: 10.1016/j.aller.2010.12.009. Epub 2011 Apr 14.

  PMID: 21497011 BACKGROUND

• Sticherling M, Franke A, Aberer E, Glaser R, Hertl M, Pfeiffer C, Rzany B, Schneider S, Shimanovich I, Werfel T, Wilczek A, Zillikens D, Schmidt E. An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone. Br J Dermatol. 2017 Nov;177(5):1299-1305. doi: 10.1111/bjd.15649. Epub 2017 Oct 29.

  PMID: 28494097 BACKGROUND

• Rashid H, Lamberts A, Diercks GFH, Pas HH, Meijer JM, Bolling MC, Horvath B. Oral Lesions in Autoimmune Bullous Diseases: An Overview of Clinical Characteristics and Diagnostic Algorithm. Am J Clin Dermatol. 2019 Dec;20(6):847-861. doi: 10.1007/s40257-019-00461-7.

  PMID: 31313078 BACKGROUND

• Reunala T, Salmi TT, Hervonen K. Dermatitis herpetiformis: pathognomonic transglutaminase IgA deposits in the skin and excellent prognosis on a gluten-free diet. Acta Derm Venereol. 2015 Nov;95(8):917-22. doi: 10.2340/00015555-2162.

  PMID: 26059085 BACKGROUND

MeSH Terms

Conditions

Pemphigoid, Bullous; Blister

Interventions

Prednisolone; Dapsone; Methotrexate

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sulfones; Sulfur Compounds; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rituparna Maiti, MD

  Professor

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor

Model Details: randomized, add-on, active-controlled, open-label, parallel-design clinical trial

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 9, 2023
• Study Start: August 1, 2023
• Primary Completion: January 3, 2025
• Study Completion: April 1, 2025
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)