Rituximab Tops Mycophenolate Mofetil for Pemphigus Vulgaris

Significantly more patients with moderate-to-severe pemphigus achieved complete remission with rituximab (Rituxan) than with mycophenolate mofetil (MMF), a randomized trial showed.

At 1 year, 40% of patients treated with rituximab had complete clearance as compared with 10% of patients randomized to MMF. Rituximab treatment was associated with a significantly reduced need for glucocorticoids and with a dramatic reduction in the number of disease flares.

Quality-of-life scores improved more with rituximab, but MMF was associated with fewer serious adverse events (SAEs), reported Victoria Werth, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, and colleagues in the New England Journal of Medicine. The results were reported simultaneously at the International Society for Pharmacoeconomics and Outcomes virtual meeting.

“Reduction in glucocorticoid use is a goal in the treatment of pemphigus vulgaris,” the authors wrote. “In this trial, more patients in the rituximab group than in the mycophenolate mofetil group were able to discontinue glucocorticoids, and patients in the rituximab group had lower cumulative glucocorticoid exposure than those in the mycophenolate group over 52 weeks. As is consistent with the greater use of glucocorticoids in the mycophenolate mofetil group, more grade 3 or higher glucocorticoid-related adverse events occurred in the mycophenolate mofetil group than in the rituximab group.”

“Further trials are needed to determine the comparative efficacy and safety of these drugs beyond 52 weeks of treatment,” they concluded.

Both rituximab and MMF are widely used to treat pemphigus. Rituximab, an anti-CD20 antibody, has a first-line indication for pemphigus in the U.S. and Europe. MMF, an immunosuppressant, is a first-line glucocorticoid-sparing agent. A randomized trial comparing glucocorticoids with or without rituximab showed better outcomes with the combination. In contrast, a randomized placebo-controlled trial showed no additional benefit from the combination of MMF and glucocorticoids.

Despite both drugs’ use as first line, limited data exist relative to the drugs’ comparative safety and efficacy. Werth and colleagues reported findings from the randomized PEMPHIX trial, which compared rituximab and MMF, each in combination with a tapering glucocorticoid regimen.

Investigators enrolled adults with pemphigus confirmed by histology, immunofluorescence, or serology. Patients had moderate or severe pemphigus as determined by a Pemphigus Disease Area Index (PDAI) score ≥15, daily glucocorticoid therapy at a dose of 60-120 mg, and clinician expectation of a benefit from the addition of immunosuppressive therapy.

Randomized treatment continued for 52 weeks, and the primary endpoint was complete remission at week 52, defined as a PDAI score of 0 (healing of all existing lesions and no new lesions). Secondary endpoints were cumulative glucocorticoid dose, number of disease flares, and change in Dermatology Life Quality Index (DLQI) scores.

Data analysis included 135 patients who had a median age of 48. Women accounted for 53% of the study population, which had a median pemphigus duration of 1.4 years. Median baseline PDAI score was 20.3, and 69% of patients had mucocutaneous disease involvement.

The primary analysis showed a four-fold difference in the proportion of patients who were in complete remission at 52 weeks (P<0.001). The rituximab arm had a mean cumulative steroid dose of 3,545 mg versus 5,140 mg for the MMF arm (P<0.001). Six disease flares occurred in the rituximab arm as compared with 44 in the MMF arm, representing an 88% reduction in the hazard ratio (95% CI 0.05-0.29, P<0.001).

A post hoc analysis suggested a greater reduction in pathogenic anti-Dsg3 autoantibodies with rituximab. However, the drugs had a similar effect on anti-Dsg1 autoantibodies over the course of the trial.

DLQI scores improved in both groups but significantly more in the rituximab arm (8.81 vs 6.00, P=0.001). An exploratory analysis showed that 62% of rituximab-treated patients had a DLQI score of 0 after 52 weeks, indicating no adverse impact of the disease on quality of life, as compared with 25% in the MMF arm.

Adverse events (AEs) occurred in 87% of all patients and did not differ appreciably between treatment groups. Serious AEs occurred in 22% of the rituximab arm versus 15% of the MMF group. The most common AEs with rituximab were infusion-related reactions (22%), headache (15%), lymphopenia (12%), and upper respiratory tract infection (10%). AEs in the MMF arm consisted primarily of diarrhea (10%) and nasopharyngitis (12%).