Rituximab May Provide Alternative Treatment Option for Epidermolysis Bullosa Acquisita

Epidermolysis bullosa acquisita | Image credit: DermNet

A recent systematic literature review published in the Journal of Clinical and Aesthetic Dermatology analyzed previous studies on the treatment of epidermolysis bullosa acquisita (EBA) with rituximab to determine whether rituximab may be a safe option for patients with the rare disease. After selecting 63 studies to review, Kianfar et al found that most patients achieved a positive clinical response with mild rituximab-related adverse events. According to the authors, the findings of their review suggest that rituximab is safe and efficacious to use in patients with EBA.¹

EBA is a rare bullous disease that is triggered by IgG autoantibodies against collagen VII (COL7). The non-inflammatory mechanobullous subtype (MB) presents as “trauma-induced tense blisters mainly limited to the skin,” whereas the inflammatory subtype includes widespread vesiculobullous involvement. According to Kianfar et al, finding the best treatment options for patients with EBA remains challenging, however, rituximab may be an ideal alternative treatment. Rituximab is a chimeric anti-CD20 monoclonal antibody that was first approved by the FDA in 1997 for the treatment of certain types of non-Hodgkin's lymphoma in adults.²

“It is expressed on a wide range of B cells, from pre-B cell stage and on mature B cells in the bone marrow and in the periphery. Since B cells play a crucial role in the pathogenesis of EBA, this disease might benefit from this treatment,” wrote Kianfar et al.

Methods

Using keywords related to “EBA” and “RTX,” Kinafar et al searched for studies on PubMed, Embase, Scopus, and Web of Science. The initially identified studies were independently screened by 2 reviewers and duplicate studies were removed. To qualify for Kianfar et al’s review, an EBA diagnosis had to be confirmed by histological, direct/indirect immunofluorescence, enzyme-linked immunosorbent assay, and/or immunoblotting assessments.

Kianfar et al pulled study characteristics, patients’ demographics, EBA subtype, disease duration until infusion, previous treatments, indication of rituximab infusion, protocol of rituximab infusion, adjuvant therapy, time to obtain clinical response, clinical remission, side effects of RTX, and treatment durability from the collected studies.

Overall, the systematic search collected 565 articles, 238 of which were not duplicates. After screening titles and abstracts, 63 studies were selected for full-text review, and 31 studies including 68 patients with EBA had eligible data.

Results

From the 31 studies, the mean age of patients was 52.9 years old, with 35 (51.5%) women and 33 (48.5%) men. The EBA subtype was defined in 43 patients, including 23 (53.5%) with MB type, 19 (44.2%) with non-MB type, and one (2.3%) with mixed form. According to Kianfar et al, the appropriate clinical response to rituximab was observed in 63 patients (92.7%).

Regarding various end points, disease remission was the primary end point in 28 of the 31 studies (61 patients), which demonstrated an overall remission rate of 73.8% (45 patients). Treatment durability was assessed in 17 studies (38 patients) and the disease relapse rate was measured as 39.5% (15 patients) in the mean follow-up of 23 months. Out of the total patients, 11 (28.2%) had rituximab-related adverse effects, which were “primarily mild and transient.” More severe adverse effects included pneumonia in 2 patients which resulted in death, and deep vein thrombosis in one patient.

Conclusions

According to Kianfar et al, due to the rarity of and lack of clinical trials on EBA and alternative treatments, mainly patients are treated with immunosuppressive therapies and fail to achieve disease remission. Despite the potential efficacy of rituximab for EBA, Kianfar et al noted that safety related to infections may still be a concern.

“The prolonged B cell depletion and unselective removal of antibodies bear an increased risk of opportunistic infections to the patients... The only major safety concern is the higher risk of infection, which should be considered before administration in vulnerable patients. The combination therapy with intravenous immunoglobulin and immunoadsorption could provide further clinical benefits,” concluded Kianfar et al.

References

1. Kianfar N, Dasdar S, Marashi A, Tavakolpour S, Mahmoudi H, Daneshpazhooh M. Rituximab in the treatment of epidermolysis bullosa acquisita: a systematic review. J Clin Aesthet Dermatol. 2024;17(7):24-36.
2. Hanif N, Anwer F. Rituximab. StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Updated 2024 Feb 28. https://www.ncbi.nlm.nih.gov/books/NBK564374/