Rituximab is superior to mycophenolate mofetil in the management of patients with moderate to severe pemphigus vulgaris, a new study shows.
A phase 3 international trial, published in the NEJM, randomised 135 patients to either IV rituximab or oral mycophenolate, in addition to oral prednisone tapered to discontinuation by 24 weeks.
The US-led study found the primary efficacy endpoint – sustained complete remission at week 52 – was achieved by 40% of patients in the rituximab group and 10% of patients in the mycophenolate group (HR 4.83; p<0.001).
A secondary end point – mean cumulative dose of oral glucocorticoids over 52 weeks – also supported the superiority of rituximab over mycophenolate (3,545 mg v 5,140 mg; p <0.001).
There were six flares in the rituximab group versus 44 in the mycophenolate group (p <0.001).
The mean change from baseline in the Dermatology Life Quality Index (DLQI) was -8.87 points with rituximab versus -6.00 with mycophenolate (p=0.001).
The study found adverse events were common in both groups (85% v 88%) with serious adverse events more common with rituximab (22% v 15%). Serious infections in the rituximab group included pneumonia, URTI, cellulitis and acute pyelonephritis.
Glucocorticoid-related adverse events of grade 3 or higher were observed in 1% of patients on rituximab and 7% of mycophenolate patients. However rates of drug discontinuation due to adverse events were 9% in both treatment groups.
The investigators said mycophenolate is the recommended first-line, glucocorticoid-sparing treatment for moderate to severe pemphigus.
“Further trials are needed to determine the comparative efficacy and safety of these drugs beyond 52 weeks of treatment,” they concluded.
Meanwhile, an Australian-led phase 2 trial of the BTK inhibitor rilzabrutinib has found half (52%) of a small group of patients achieved the primary endpoint of control of disease activity (CDA) with zero to low corticosteroids by week 4.
The CDA rate improved over time to 70% by week 12 and 85% after an additional 12 weeks of therapy.
“Excitingly, the rapid achievement of CDA (median 33 days) by patients without moderate-to-high CS doses, suggests the possibility of a CS-free rilzabrutinib acute control regimen for future patients, or at least one with a rapid CS taper to minimise CS-related adverse effects,” the study said.
The study authors, led by Professor Dedee Murrell from St George Hospital and the University of NSW, said the safety results indicated a favourable risk/benefit profile for rilzabrutinib.
“Most treatment-related TEAEs were mild (grade 1/2) and transient, with no reported cases of AEs commonly associated with marketed irreversible BTK inhibitors (eg, major haemorrhage, atrial fibrillation, thrombocytopenia/neutropenia).”
“Additionally, rilzabrutinib enabled reduced initial CS doses and facilitated rapid tapering, a major goal in pemphigus therapies.”
A phase 3 of rilzabrutinib versus placebo with CS taper is underway.