Autoimmune diseases

Two trials compare treatments for pemphigus vulgaris


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.

However the findings from their current study are consistent with other evidence – here and here – of rituximab’s efficacy.

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

BTK inhibition

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.

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