Rituximab Treatment Effective in Disease Remission in AAV: Study
Therapy for 6 months leads to remission in 2/3 of GPA, MPA patients
Up to six months of treatment with rituximab led to disease remission in about two-thirds of Japanese patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), a study found.
Further, people in Japan with these two types of ANCA-associated vasculitis (AAV) who were given rituximab as a maintenance therapy also maintained their remission status for at least half a year.
“This study investigated effectiveness and safety of [rituximab] in clinical practice in Japan to enhance AAV treatment,” the researchers wrote, noting a “lack of evidence and clinical experience” with rituximab treatment in the Asian nation despite the therapy’s long-time approval.
Titled “Nation-wide Cohort Study of Remission Induction Therapy using Rituximab in Japanese patients with ANCA-Associated Vasculitis: effectiveness and safety in the first six months,” the study was published in the journal Modern Rheumatology.
Cyclophosphamide treatment favored over rituximab
AAV is a group of inflammatory diseases characterized by damage to small blood vessels in multiple organs and tissues. This occurs due to the production of self-reactive antibodies, called antineutrophil cytoplasmic antibodies, or ANCAs, that abnormally activate certain immune cells against the cells lining blood vessels.
Rituximab, sold as Rituxan among others, is an antibody-based therapy designed to reduce the number of B-cells, the immune cells involved in producing antibodies, including the self-reactive ANCA antibodies.
Given directly into the bloodstream (intravenously), the therapy is approved in the U.S., Europe, and Japan for GPA and MPA. It’s indicated both for inducing remission in patients with active disease and as a maintenance therapy when remission has been achieved.
However, approvals were based on clinical trials conducted in the U.S. and Europe, and the lack of trial data involving Japanese patients has led health authorities in the country to favor cyclophosphamide over rituximab as a remission induction therapy for AAV patients. Indeed, guidelines dating to 2017 recommend cyclophosphamide treatment over rituximab.
To investigate the safety and efficacy of rituximab among patients in Japan, the Ministry of Health, Labour and Welfare for Intractable Vasculitis (JPVAS) implemented an observational study to follow GPA and MPA patients receiving the therapy at several Japanese centers.
Called RemIRIT (UMIN000020329), the study included 79 patients, ages 20 and older, who received rituximab treatment between 2015 and 2017. Among them, 75 were given the medication to induce remission and four received rituximab as a remission maintenance therapy.
The trial’s main goal was to determine the proportion of patients in the remission-induction group who achieved remission within six months. Secondary measures included survival and relapse rates.
Of those receiving the therapy for remission induction, 53 (70.7%) achieved remission in the first six months of treatment. Remission determination was based on a score of 0 on the Birmingham vasculitis activity score (BVAS), a measure of disease activity, obtained in two successive evaluations at least one month apart.
However, only 50 of those patients maintained their remission status at six months of follow-up.
Notably, while researchers set out to identify factors that could predict patients not likely to achieve remission while on rituximab, none of the factors included in the analysis was significantly associated with that clinical outcome.
“As achieving and maintaining remission is a primary goal in the treatment of MPA and GPA, it is critical to identify factors that prevent achieving remission,” the researchers wrote.
In terms of safety, 24 patients experienced serious side effects and 16 patients had serious infections. A total of nine patients died, primarily due to infections of disease exacerbations.
The incidence of serious side effects, serious infections, and deaths all were significantly more common among patients who failed to achieve remission compared with those who did.
According to the researchers, “it is possible that the occurrence of [serious infections] affected the treatment content, resulting in failure to achieve remission, or that treatment resistance affected the intensity of treatment, resulting in the occurrence of [serious infections] and non-achievement of remission,” they wrote.
The results also showed that older age (75 and older) and the presence of lung complications were risk factors for the development of serious infections — both increased the risk of this side effect by 3.5 times.
The team noted that “safety should be prioritised” in people with multiple risk factors. To that end, they proposed some “definite countermeasures” to reduce the frequency of serious infections during rituximab treatment. Among them were the “reduction of [glucocorticoid] dose and prophylaxis [preventive treatment] against some infectious diseases.”
Overall, the researchers concluded, “the proportion of remission by 6th month was high in patients with MPA and GPA starting [rituximab].”
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