Rituximab beats mycophenolate mofetil in pemphigus vulgaris

Pemphigus vulgaris patients had a 5 times greater likelihood of achieving a complete remission when treated with rituximab compared mycophenolate mofetil (MMF). In addition, the anti-CD20 monoclonal antibody had a superior safety profile.

Prof. Pascal Joly (Rouen University Hospital, France) presented the results of the randomised, clinical, phase 3 PEMPHIX trial, which compared rituximab head-to-head with MMF for the treatment of pemphigus vulgaris [1]. Although MMF is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, its efficacy has never been proven in a clinical trial. In contrast, rituximab was approved earlier this year by the US authorities and the European Commission for the treatment of adults with moderate-to-severe pemphigus vulgaris. It is the first approved biologic, and therefore a major advancement in the treatment of this rare blistering disease, which can lead to serious, life-threatening fluid loss, infection, and death.

Approval was based on data from the phase 3 Ritux 3 trial, which was also led by Prof. Joly. Ritux 3 demonstrated the superiority of intravenously administered rituximab plus short-term prednisone over high-dose corticosteroid monotherapy [2].

In the more recent phase 3, placebo-controlled PEMPHIX trial, 135 patients with moderate or severe pemphigus were randomised at 49 centres in 10 countries to double-blind rituximab (n=67) or MMF (n=68). The study drug was given on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months. Primary endpoint of the study was the proportion of patients at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. In the rituximab arm, 66 patients completed week 52 compared with 58 patients in the MMF arm.

At week 52, 40.3% of patients in the rituximab arm achieved the primary endpoint compared with 9.5% with MMF (P<0.0001). In addition, rituximab was superior in all secondary efficacy endpoints: patients in the rituximab group had a significantly lower cumulative oral corticosteroid dose: the median cumulative dose was 2,775 mg in the rituximab group compared with 4,005 mg in the MMF group (P=0.0005). The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm versus 4 g with MMF. A significantly fewer number of flares occurred in patients treated with rituximab compared with MMF (6 vs 44 in the MMF arm; P<0.0001). Five rituximab-treated patients experienced disease flares, in contrast to 26 treated with MMF.

The higher efficacy translated into a significantly greater improvement in health-related quality of life in patients treated with rituximab, assessed with the Dermatology Life Quality Index (DLQI): 61.5% of patients in the rituximab arm had achieved a DLQI score of 0 (i.e. no impairment in health-related quality of life) at week 52 compared with 25% of patients in the MMF arm. Rituximab showed an acceptable tolerability: 9% of the rituximab group and 7.4% of MMF-treated patients had 1 or more treatment related adverse event, a non-significant difference. Serious infusion reactions leading to study withdrawal occurred in 3 patients on rituximab and 1 on MMF. There was a significant difference in favour of rituximab regarding the rate of grade 3 or worse corticosteroid-related adverse events. This was observed in 1.5% of patients with rituximab versus 7.4% with MMF. Overall, rituximab had a superior benefit-risk profile compared with MMF in patients with pemphigus vulgaris. “These results probably mean the end for MMF in pemphigus vulgaris,” said Prof. Joly.

1. 
   
   1. Joly P, et al. Late-breaking abstract D3T01.1C, EADV 2019, 9-13 Oct, Madrid, Spain.
   2. Joly P, et al. Lancet 2017;389:2031-40.

Posted on 9 December, 201912 March, 2021