Medication Dose Increased Likeliness of Remission for Patients with Pemphigus

The research team findings suggest that the more aggressive lymphoma approach gives a patient the best chance for complete remission off oral immune suppressants.

New research from a team in the Perelman School of Medicine at the University of Pennsylvania shows that a lymphoma-dose regimen of rituximab, a medication regularly used to treat lymphoma and rheumatoid arthritis, is more likely to put patients with pemphigus into complete remission as compared to a RA regimen of the same medication.

The findings were published in JAMA Dermatology.

Pemphigus, an autoimmune disease mediated by B cells, causes painful blisters and sores on the skin and mucous membranes. It is a rare chronic autoimmune condition that can be fatal if not treated.

When rituximab, an antibody which was first used to treat B cell lymphoma, became a treatment for pemphigus vulgaris, clinicians could choose to prescribe either a “lymphoma dose” or an “RA dose.”

A lymphoma-dose regimen of rituximab is a more aggressive approach to treatment compared to the dosing method for patients with rheumatoid arthritis. The FDA has approved dosing regimen for pemphigus vulgaris, but it closely resembles the often less-effective RA dose.

While both lymphoma and RA dosing approaches deplete B cells that cause disease, the lymphoma regimen takes into account a person’s height and weight to determine a dose and is given weekly for 4 weeks. A rheumatoid arthritis dose is a fixed dose of two 1000mg infusions given 2 weeks apart.

The odds of complete remission for patients on a lymphoma regimen were 2.7 times greater compared to patients on a RA regimen, suggesting that the FDA-approved regimen for pemphigus may not be ideal.

Like pemphigus, rheumatoid arthritis is a B cell-mediated autoimmune disease, as opposed to a B cell cancer where the total number of B cells greatly exceeds those in an autoimmune patient. Because the FDA-approved dose of pemphigus vulgaris is the same as the RA dose, some patients have insurance that only covers the RA regimen of the expensive medication. Rituximab is also an immunosuppressant, so higher doses may risk higher rates of infection.

The research team’s findings suggest that the more aggressive lymphoma approach gives a patient the best chance for complete remission off oral immune suppressants, which is the desired outcome.

The research team found that the odds of achieving complete remissions in patients over age 65 was almost 10 times greater than those under 45, and patients with moderate to severe obesity had over 7 times lower odds of achieving complete remission compared to non- or mildly obese patients.

The evidence supports the use of rituximab in general for treating pemphigus. Before the medication, the only FDA-approved treatment option was a course of steroids. Looking at rituximab’s success in both dosing regimens combined, the study showed 48% of patients achieved complete remission after just one cycle of the drug. With repeated cycles, complete remission jumped to 71%.

While 5% of the patients in this study developed serious infections over the course of rituximab treatment for pemphigus, that's still lower than historical rates in patients who receive high-dose steroid therapy for the disease -- another reason to suggest rituximab is a suitable treatment, although larger studies would be necessary to determine if the risk of serious infection is significantly higher between the lymphoma and RA regimens.


Carolyn J. Kushner, Shiyu Wang, Napatra Tovanabutra, Donald E. Tsai, Victoria P. Werth, Aimee S. Payne. Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus. JAMA Dermatology, 2019; DOI: 10.1001/jamadermatol.2019.3236