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

Bullous Pemphigoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05984381
• Other study ID #: AIIMS BBSR/PG Thesis/2023-24
• Status: Recruiting
• Phase: Phase 4
• Start date: August 1, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: December 2023
• Source: All India Institute of Medical Sciences, Bhubaneswar
• Contact: Monalisa Jena, MD
• Phone: 9438884193
• Email: pharm_monalisa[@]aiimsbhubaneswar.edu.in
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: December 1, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bullous Pemphigoid
• Pemphigoid, Bullous

Intervention

Drug:
• Prednisolone
prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally
• Dapsone
Dapsone 100 mg/day
• Methotrexate
Methotrexate 15 mg weekly

Locations

Country	Name	City	State
India	AIIMS Bhubaneswar	Bhubaneswar	Odisha

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, Bhubaneswar

Country where clinical trial is conducted

India, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	change in serum BP180	change in serum BP180 after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone	16 weeks
Secondary	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
Secondary	the cumulative prednisolone dose	cumulative prednisolone dose after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone	16 weeks
Secondary	time to the initial flare	time to the initial flare after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone	16 weeks
Secondary	number of flares in study groups	number of flares in study groups after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone	16 weeks
Secondary	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
Secondary	treatment-emergent adverse events	treatment-emergent adverse events in both the groups	16 weeks