The Effectiveness of Rituximab in Pemphigus and the Benefit of Additional Maintenance Infusions

• This retrospective review analyzed the efficacy of rituximab, with or without maintenance infusions, in pemphigus patients. All patients (N=53) received two initial infusions of 1000 mg 2 weeks apart; 25 patients also received maintenance infusions at 6 and 12 months, whereas the rest received maintenance infusions on clinical indication only. The relapse rate was significantly lower in the group receiving systematic maintenance infusions (40% vs 71%; P = .024), which remained true after correcting for pemphigus subtype, rituximab naïve or non-naïve, disease duration, and mean cumulative dose of prednisone. Of the total, 12 (23%) achieved partial remission and 41 (77%) achieved complete remission at 3 years. Only 7% of reported severe adverse events, although none were life-threatening.

• This study demonstrated that the systematic use of maintenance infusions of rituximab at month 6 and 12 decreased relapse rate in pemphigus patients. Ultimately, all patients achieved partial or complete remission at 3 years, indicating the efficacy of rituximab in treating this disease.

– Margaret Hammond, MD

Written by

 

 

Jeffrey P. Callen MD

Rituximab is currently the only FDA-approved therapy for pemphigus vulgaris and pemphigus foliaceus. It is now often used in patients who are naïve to therapy, but previously has been used in patients on corticosteroids and/or traditional immunosuppressive therapies. It is administered via infusion, and there is a risk of infusion reactions, reactivation of hepatitis B, and possible progressive multifocal leukoencephalopathy along with other potential toxic reactions. For patients with pemphigus, its use has at times resulted in complete and long-lasting remission of disease.

What is not known is the best dosing of the drug initially and whether any maintenance therapy is needed. This current research letter addresses the latter issue. The authors retrospectively analyzed 53 patients who were either treated with initial therapy of 1000 mg infused on day 1 and repeated at day 15. Some of the patients were then treated on a protocol of 500 mg at 6 months and 12 months whereas others were only treated if symptoms or signs were present. They found that those on maintenance therapy were more likely to avoid relapses than those not treated with this standardized regimen. They note that limitations include the heterogeneity of the populations treated and the lack of use of a validated scoring system. In addition, I would list the small sample size as another limitation. They also did not report on antibody levels as a potential guide to a decision to treat in their patients.

Bottom line: It appears that relapse of pemphigus is avoided by administering rituximab at 6 and 12 months after initial infusions.

Written by

 

 

Joseph Kamel DO 

Written by

 

Neil J. Korman MD, PhD

Until recently, the anti-CD20 antibody rituximab was only used to treat the most refractory cases of pemphigus because it did not have an FDA approval. Based upon robust clinical trial data, rituximab achieved FDA approval in 2018 for adults with pemphigus vulgaris. Since 2018, rituximab continues to become more widely accepted as the first-line treatment for patients with pemphigus vulgaris due to excellent efficacy and safety. The dosing of rituximab includes two intravenous infusions of 1000 mg given at weeks 0 and 2 followed by a 500-mg maintenance dose at 12 months and every 6 months thereafter.

In this retrospective study of a group of pemphigus patients in the Netherlands, the authors evaluated the potential benefit from maintenance rituximab infusions. In a cohort of 53 patients who received an additional 500-mg rituximab infusion at 6 months and 12 months after the initial two 1000-mg infusions, the relapse rate within the first 3 years was 40% compared with 71% in those without maintenance therapy. Although efficacy parameters were similar between groups, these data suggest a beneficial effect on preventing relapses with 500-mg maintenance doses at 6 months and 12 months from the initial infusions. While these data support the use of maintenance rituximab therapy in patients with pemphigus vulgaris, future larger studies to determine the optimal dose and frequency are needed to minimize the rate of relapse.

Abstract 

Rituximab is addressed as first-line therapy in pemphigus.1 Additional maintenance infusions are often given on clinical indication, but evidence regarding these infusions is scarce. The aim of this study was to analyze the effectiveness of rituximab, with and without maintenance infusions. Retrospective data was obtained from patients with PV and PF treated with rituximab between 2012 and 2017. Two infusions of 1000mg were administered with an interval of two weeks (M0 and M1/2). From 2014, patients received additional maintenance infusions of 500mg at month 6 and 12 (M6 and M12) as standard protocol (systematic infusions).

Journal of the American Academy of Dermatology

The Effectiveness of Rituximab in Pemphigus, and the Benefit of Additional Maintenance Infusions: Daily Practice Data From a Retrospective Study

J Am Acad Dermatol 2020 Jun 12;[EPub Ahead of Print], H Rashid, A Lamberts, D van Maanen, MC Bolling, GFH Diercks, HH Pas, MF Jonkman, B Horváth 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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