There is still a clinical need for corticosteroid-sparing treatments for immunobullous disease in Australia and the availability of rituximab as a first-line treatment would do much to fill the gap.
The monoclonal antibody directed against CD20-expressing B-lymphocytes was FDA listed for this indication in 2018 and by the European Medicine Agency (EMA) in March this year.
The ACD ASM was told the listings were based on a 2017 study published in The Lancet, which showed first-line use of rituximab plus short-term prednisone for patients with pemphigus was superior to prednisone alone and with fewer adverse events.
Dr Gary Unglik, an allergist and immunologist from the Royal Melbourne Hospital, told the limbic the study provided high-level evidence that wasn’t always available in such rare diseases.
“That is the most recent and the best evidence that it clearly works and the good thing about that trial is that it was comparing rituximab to the standard of treatment of corticosteroids.”
Patients in the rituximab-corticosteroid group were tapered off prednisone within 3-6 months while patients in the prednisone-only group were tapered over 12-18 months.
“And they showed that the people who were given the rituximab, had much less cortisone, they had fewer adverse events, and they had significant improvement in their disease.”
“87% were free of disease off-therapy two years down the track versus 30% who had been given the steroids. So it’s really very clear evidence that it is very effective.”
He told the meeting that while there was variation in response to rituximab, the evidence showed that healing usually started within weeks, with a median time to clinical remission of 3-6 months. The median duration of remission was 15-19 months.
Precautions before commencing patients on rituximab included screening for hepatitis B, having relevant immunisations up to date and discussing the rare potential side effect of progressive multifocal leukoencephalopathy.
Dr Unglik said patient groups or treating doctors will need to advocate for TGA and PBS listing for rituximab for this indication.
“These are really rare diseases and the fact they are rare diseases means that that the evidence has always been a little sketchy,” he said.
However the now strong evidence that rituximab was more effective and safer than corticosteroids should tip the balance over the drug’s high cost.
Professor Enno Schmidt, from the Lubeck Institute for Experimental Dermatology in Germany, told the meeting that that add-on therapy included intravenous immunoglobulin, anti-neonatal Fc receptor and desmoglein-specific immunoadsorption.
Other emerging therapies for immunobullous disease included selective Bruton’s tyrosine kinase inhibitors and chimeric autoantibody receptor T-cell therapy, he said.