乌鸦传媒

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

At 1 year, 40% of patients treated with rituximab had sustained complete remission after ≥16 weeks off prednisone, 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 . The results were reported simultaneously at the virtual meeting.

"This study showed that rituximab is superior to MMF in achieving sustained complete remission off corticosteroid for 16 weeks or more, and is supported by significantly less cumulative corticosteroid exposure, fewer relapses, higher likelihood of sustained complete remission, lower risk of relapse, and a greater improvement in quality of life," Werth told 乌鸦传媒 via email. "Given the manageable safety profile with an acceptable tolerability in this population, rituximab has a superior overall benefit-risk profile compared to MMF in patients with moderate to severe pemphigus vulgaris."

Both rituximab and MMF are widely used to treat pemphigus. Rituximab, an anti-CD20 antibody, has a first-line indication for pemphigus in the and . MMF, an immunosuppressant, is a first-line glucocorticoid-sparing agent. A comparing glucocorticoids with or without rituximab showed better outcomes with the combination. In contrast, a randomized placebo-controlled trial showed from the combination of MMF and glucocorticoids.

Despite both drugs' use as first line therapy, limited data exist relative to the drugs' comparative safety and efficacy. Werth and colleagues reported findings from the randomized , 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 sustained complete remission (PDAI score of 0), off prednisone for at least 16 weeks, at week 52. 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 sustained 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%).

The authors stated that additional studies are needed to determine the comparative efficacy of rituximab and MMF beyond 52 weeks.

Comment