Role of Rituximab in the Treatment of Pemphigus Vulgaris: Patient Selection and Acceptability

Abstract

Anti-CD20 monoclonal antibody rituximab is an approved adjuvant treatment, in combination with oral corticosteroids, for patients with pemphigus vulgaris, a severe and potentially life-threatening autoimmune blistering skin disorder. Updated approaches to the management of pemphigus vulgaris support rituximab as a first-line adjuvant treatment to induce remission early in the course of disease; however, its feasibility in the clinical setting is often reduced by a series of limitations, including high cost of this biological drug, physician and patient concern for the risk of adverse reactions, and uncertainty regarding the optimum dosing and schedule of administration. The standard approved rituximab dosages, which are derived from lymphoma protocols, have been recognized to exceed the effective dose required for inducing B cell depletion, since the B cell burden in pemphigus vulgaris is much lower than in lymphoproliferative disorders. To overcome these limitations, recent research has investigated alternative regimens of rituximab, using lower doses of the drug. Moreover, differences in patient and disease characteristics that are highlighted in the literature strongly suggest that therapy should be tailored individually on a case-by-case basis: personalized treatment schedules may be necessary to optimize response to treatment and tolerability in different subjects, with the possibility of repeated infusions for severe forms and in case of relapse. Finally, low-dose regimens of rituximab were suggested to be favorable during the COVID-19 pandemic by providing a lesser degree of immune cell depletion while retaining a sufficient response. In conclusion, the current literature suggests that lower-dose regimens of rituximab are not only tolerable and cost-effective but may also be associated with a positive response in pemphigus vulgaris, comparable to that achieved with higher doses especially in early disease. Further evidence from rigorous clinical trials will be required to optimize lower-dose regimens of RTX and establish their position within the treatment scenario of pemphigus vulgaris.

Is It Time to Reconsider Rituximab Dosing Regimens for Pemphigus Vulgaris?

“…All these concerns have prompted clinicians to explore alternative dosing protocols. The authors of the present article recently reviewed lower-dose regimens of RTX for the treatment of PV, highlighting how the existing literature supports the use of low-dose and ultra-low-dose RTX protocols to treat PV, with the possibility of repeated infusions for more severe cases [ 7 ]. It is important to highlight that dose-defining trials for PV are missing.…”

“…Conventional RTX dosing regimens for PV, initially adapted from the protocols used in lymphoproliferative diseases, may exceed the required doses for inducing B-cell depletion. Recent studies support low-dose and ultra-low-dose RTX regimens for PV treatment [ 6 , 7 ].…”

The Transition from Pemphigus Foliaceus to Pemphigus Vegetans—An Intriguing Phenomenon within the Spectrum of Autoimmune Blistering Diseases: A Case Report

“…The treatment with rituximab led to a very positive response in the case of our patient, with a significant improvement of his skin lesions. Even if in the past rituximab has been an off-label option for the treatment of patients with resistant pemphigus, recent evidence shows that the use of rituximab as a first-line treatment could be a safe treatment choice for managing patients with severe forms of pemphigus [14][15][16][17].…”