Benjamin Terrier, MD, PhD: Rituximab for Eosinophilic Granulomatosis with Polyangiitis

Rheumatology Network interviewed Benjamin Terrier, MD, PhD, to discuss his study and ACR presentation, “Rituximab versus Conventional Therapeutic Strategy for Remission Induction in Eosinophilic Granulomatosis with Polyangiitis: A Double-blind, Randomized, Controlled Trial.” Terrier is a Professor of Internal Medicine at Cochin Hospital in France.

Rheumatology Network: Can you give me a bit of background on eosinophilic granulomatosis with polyangiitis (EGPA) and what inspired your team to study the efficacy of rituximab for treating this condition?

Benjamin Terrier, MD, PhD: EGPA is a systemic disease belonging to the family of anca associated vasculitis. So, it's inflammation of the vessel walls that are associated with antibodies against the neutrophils type of white blood cells that we named anca. And so far, there was almost no studies evaluating the treatments in EGPA, because it's a rare disease. The management was based on all the studies that evaluated the efficacy of the conventional immunosuppressive agents, mainly glucocorticoids and immunosuppressive agents like cyclophosphamide and azathioprine. In the recent French and US recommendation to manage this disease, the question of rituximab efficacy was raised mainly because in the 2 other diseases belonging to the same family, rituximab was demonstrated to be a major treatment. But the pathophysiology of EGPA is a little bit different. That's why we had to evaluate in a prospective, randomized, double-blind study the efficacy of rituximab. Some really small retrospective studies suggested that it could be an effective therapy.

RN: What was the study design that your team developed?

BT: We did a parallel group phase 3 study, which was the comparison of a rituximab-based regimen. So, a combination of glucocorticoids plus rituximab, compared to the conventional strategy, which is based on the severity of the disease. We have a tool, a 5 factor score, which is an a list of 5 items and if there if there isn't at least 1 of these items, the disease is considered to be severe. If there are no items, it's a non-severe disease. The conventional strategy is, in case of non-severe disease, you treat with glucocorticoids alone, and in case of severe disease, you treat with a combination of glucocorticoids plus cyclophosphamide.

RN: And what were the results of your study?

BT: The main results is, first, it was a superiority research. So we made the hypothesis that rituximab could be more effective than the conventional strategy. The first result is that it's a negative study showing that rituximab is not superior to the conventional strategy. The rate of complete remission, which was evaluated at 6 months, day 180, showed very similar results. So, it means that for the primary outcome, and for all the secondary outcome, the results were extremely similar between the 2 groups. We can consider that It's negative study. But we could also consider that maybe in some conditions, rituximab could be an alternative to cyclophosphamide, which you probably know could be really detrimental in young female, for instance, because of the toxicity on fertility. But as an epidemiological point of view, we can say that it's a similar result because it was not a non-inferiority study. We also made some subgroup analyses to identify if these results were different according to the subgroups of patients, such as the patients with anca, the patients with severe disease, and the patients with non-severe disease. The results were the same in all of the subgroups.

RN: Were you surprised by the results?

BT: Not really, because the hypothesis to get a superiority of rituximab compared to the conventional strategy was a very difficult goal to achieve. And we know that the results with the conventional strategy are quite good. So, getting superiority for rituximab was possible, but not the most probabl. But I think it was very important to make the study because so far, for instance, the very recent recommendations were recommending both cyclophosphamide or rituximab, but without getting any data. And I think now, we are able to make some recommendation based on quality data, which is always important to try to find a better management for these patients.

RN: Is there anything else that you would like our audience to know?

BT: No, I think it's important now to evaluate new strategies, especially therapy treatments targeting the interleukin 5. And I think that this study showed that we can make some academic studies in EGPA. It was the first double-blind academic study conducted so far in the world. And I think it showed that we can make some studies in this rare disease, and I hope that we and colleagues will also conduct other studies on these diseases.