Clinical trial NCT05984381: Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid
Official title: Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Bullous Pemphigoid
Keywords: Bullous pemphigoid
Methotrexate
Dapsone
BP180
Blister
Erosions
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2023-08-09
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, add-on, active-controlled, open-label, parallel-design clinical trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: change in BPDAI (Bullous Pemphigoid Disease Area Index) score
timeFrame: 8 weeks and 16 weeks
Secondary outcomes:
measure: change in serum BP180
timeFrame: 16 weeks
measure: the remission rate
timeFrame: 8 weeks and 16 weeks
measure: the cumulative prednisolone dose
timeFrame: 16 weeks
measure: time to the initial flare
timeFrame: 16 weeks
measure: number of flares in study groups
timeFrame: 16 weeks
measure: change in the Dermatological life quality index (DLQI)
timeFrame: 8 weeks and 16 weeks
measure: treatment-emergent adverse events
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Bhubaneswar
country: India
facility: AIIMS Bhubaneswar
state: Odisha
Study officials:
affiliation: Professor
name: Rituparna Maiti, MD
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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.
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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.
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.
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.
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.