Extra Rituximab Dose at Six Months May Prevent Early Relapse in Pemphigus Patients

Receiving an extra dose of rituximab at six months could help prevent early relapse in patients with moderate to severe pemphigus, according to a recent study published in JAMA Dermatology.

Pemphigus is a rare autoimmune disease that causes painful blisters on the skin and mucous membranes, including the mouth, nose, throat, eyes and genitals.

This is caused due to the immune system mistakenly attacking desmogleins, which are proteins that help skin cells stick together. When these proteins are attacked, the skin becomes weak, leading to blistering.

There are two main types of pemphigus: pemphigus vulgaris and pemphigus foliaceus.

Pemphigus vulgaris usually affects the mouth and other mucous membranes but can also involve the skin. Pemphigus foliaceus affects only the skin, causing blisters in the upper layers of the epidermis.

Although pemphigus is uncommon in the U.S., certain ethnic and genetic factors increase the risk of developing it, including Ashkenazi Jewish, Indian, Southeast European and Middle Eastern backgrounds, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

While there is no cure for pemphigus, it can often be managed with medication.

One of the most common treatments for pemphigus is rituximab, a type of monoclonal antibody that targets a protein called CD20 on B cells. By binding to this protein, rituximab marks these B cells for destruction by the immune system.

This is effective because B cells produce the antibodies that mistakenly attack desmogleins.

Despite its effectiveness, about 20% of patients treated with rituximab relapse within the first year. This led researchers to investigate whether giving an extra dose at six months could reduce relapse rates in patients who are more likely to relapse.

Researchers conducted the study in France from September 2018 to June 2023 and included 87 patients who were newly diagnosed with pemphigus.

All patients went into complete remission after receiving the RITUX 3 regimen, which is a standard rituximab treatment for pemphigus.

Researchers looked at three factors in the third month to identify patients at high risk for relapse: a Pemphigus Disease Area Index (PDAI) score of 45 or higher, anti-Desmoglein 1 (DSG1) antibodies above 20 IU/mL, and anti-Desmoglein 3 (DSG3) antibodies above 130 IU/mL.

Patients who were in complete remission at month six but showed at least one of these risk factors received an additional dose of rituximab.

The study showed that the relapse rate dropped from 17.6% to just 2.6% at one year. This suggests that by using these risk factors to guide an extra dose of rituximab, early relapse can be effectively prevented.

Researchers suggest the findings display that a more personalized approach to pemphigus treatment could be useful. Identifying high-risk patients through PDAI scores and antibody levels allows doctors to better tailor rituximab treatment to reduce the chances of relapse.

This approach may also reduce the need for corticosteroids, which are often used to control relapses but come with serious long-term side effects.

The study found no significant increase in side effects from the additional dose of rituximab, suggesting it is safe to use this approach.

However, it is suggested that more research is needed to confirm these results in larger and more diverse patient groups. Future studies could also explore whether this strategy helps in the long run by slowing disease progression and improving the quality of life for patients.

Researchers claim this study is the first to explore using an extra dose of rituximab at six months based on PDAI scores and antibody levels.