Table 1.
Evaluation of clinical and pre-clinical studies on BTK inhibitors in pemphigus diseases.
| Study ID | Study Design | Sample Size | Age (Mean) | Gender Ratio (M: male) | Type of Disease | Previous Treatment | BTK Inhibitor Treatment | Treatment Duration (weeks) | Outcome Measurement | Efficacy | Adverse events | Comorbidities | Follow-up Evaluation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Goodale, 2020 [11] | Experimental | 9 | 8.2 | M: 56% | Canine pemphigus foliaceus | None | Atuzabrutinib 15 mg/kg daily in combination with PRN prednisolone 1 mg/kg twice a day | 16–20 | Physical examination, anti-Dsc-1 titer, and Wilcoxon rank sum test | 33% near-complete remission 44% poor or fair response despite initial improvement |
Recurrence of a previously excised mast cell tumor (11%), lymphadenopathy, and Immune-mediated polyarthritis (22%) | 33% severe allergic dermatitis, 11% mast cell tumor, 11% chronic pancreatitis | Relapse following treatment break from BTKi |
| Goodale, 2020 [12] | Experimental | 4 | 9.25 | M: 25% | Canine pemphigus foliaceus | None | Rilzabrutinib, 17–33 mg/kg | 20 | cPDAI, Serum anti-Dsc-1, and Dsg-1 IgG titers | 75% near-complete remission 25% fair response |
Pyometra (25%) | Not mentioned | Not mentioned |
| Lee, 2017 [9] | Case report | 1 | 51 | M | Paraneoplastic pemphigus | Oral Corticosteroid, intravenous Corticosteroid, and Rituximab | Ibrutinib 420 mg daily in combination with rituximab | 16 | Physical examination and clinical evaluation | Decrease signs and symptoms, especially cutaneous manifestations | Florid ecchymosis and purpura | CLL | Clinical remission after total taper after 3 months |
| Murrell, 2021 [13] | Clinical trial Phase II | 27 | 51 | M: 44% | Moderate to severe pemphigus Vulgaris | High-dose corticosteroids and rituximab | Rilzabrutinib 400–600 mg twice daily with or without low-dose corticosteroid | 12 | Primary endpoint: CDA within 4 weeks. Secondary endpoint: time to receive CDA, complete remission, relapse post rilzabrutinib, and corticosteroid usage. PDAI score, anti-dsg3 antibody level |
Primary endpoint CDA; 52%, decrease mean corticosteroid dose, 22% complete remission by week 24, Improve PDAI score Decrease anti-Dsg3 antibody level |
Nausea (15%), upper abdominal pain (11%), headache (15%), cellulitis grade 3 (n = 1), | Diabetes mellitus type 2 (n = 1), congenital pulmonary sequestration (n = 1) | 12 weeks, successful treatment with Rilzabrutinib alone without moderate to high dose corticosteroids after 12 weeks |
| Ito, 2018 [10] | Case report | 1 | 62 | M | Paraneoplastic pemphigus | Bendamustine combined with rituximab | Ibrutinib 420 mg daily | Not mentioned | Physical examination and clinical evaluation | Decrease in signs and symptoms | Not mentioned | B-CLL/SLL | Not mentioned |
| Yamgami, 2021 [4] | Clinical trial Phase II | 16 | 52.5 ± 8.8 | M: 50% | Pemphigus vulgaris (50%), Pemphigus foliaceus (37.5%), and pemphigus vegetans (12.5%) |
Oral corticosteroid and adjuvant therapy | Postprandial oral tirabrutinib 80 mg once daily | 52 | Primary endpoint: complete remission after 24 weeks. Secondary endpoint: absolute remission rate over time, remission rate over time, and change in PDAI score, anti-Dsg1 and Dsg3 antibody, and oral corticosteroid exposure over time |
Complete remission rate:18.8% after 24 weeks and 50% after 52 weeks Decrease mean prednisolone dose over time Decrease anti-Dsg1 and Dsg3 titers baseline. Decrease PDAI score |
Nasopharyngitis (n = 5), influenza (n = 3), pemphigus (n = 3), hypertension (n = 3), folliculitis (n = 2), oral candidiasis (n = 2, hepatic enzyme increase (n = 2), adverse drug reaction: nasopharyngitis (n = 3) |
Not mentioned | Not mentioned |
B-CLL/SLL: B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma; CDA: control of disease activity; CLL: Chronic lymphocytic leukemia; Dsc: desmocollin; Dsg: desmoglein; Ig: immunoglobulin; PDAI: Pemphigus disease area index; mg: milligram; PRN: pro re nata.