Guidelines for using rituximab as a maintenance therapy in adults with ANCA-associated vasculitis (AAV) were recently published that, in addition to helping physicians with treatment approaches, highlight areas where more research is needed.
Rituximab works by depleting B-cells, the immune cells that produce antibodies. The therapy is approved for use as both an induction therapy and a maintenance therapy in two AAV subtypes, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
However, clinical guidance for rituximab’s use as a maintenance therapy is limited.
“These guidelines can be used to assist specialty physicians making treatment decisions in patients with AAV when RTX [rituximab] has been chosen for remission maintenance,” the researchers wrote.
These researchers — a group of 20 experts in kidney disease and/or autoimmune disease — performed an extensive review of the existing scientific literature to establish the guidelines. Guidelines were also reviewed by clinicians who weren’t directly involved in their creation, to ensure that they were practical in clinical contexts.
The team recommends rituximab maintenance therapy after induction therapy (with either rituximab or cyclophosphamide) for all three subtypes of AAV. For individuals with GPA or MPA, the recommendation was strong, based on robust evidence.
For the third type of AAV, eosinophilic granulomatosis with polyangiitis (EGPA), the guidelines make the same recommendation, but note that there is much less research supporting rituximab’s effectiveness in this “relatively understudied subgroup of AAV.”
Prompted by the need for more studies of rituximab in EGPA, a Phase 3 clinical trial, MAINRITSEG (NCT02807103), is underway and may still be recruiting up to 108 eligible adults at its single site in Paris, France, to test rituximab induction and maintenance therapy in EGPA against conventional therapy.
Two general strategies for rituximab dosing have been proposed: providing treatment at regular doses at pre-defined time intervals, or tailoring dosages based on biomarkers. The guidelines recommend the former because, at present, not enough data showed that biomarker-guided dosing is effective.
“The role of biomarker guided RTX dosing has not been proven and requires further study, including the evaluation of long-term outcomes,” the investigators wrote. “Fixed interval dosing has therefore been recommended.”
These guidelines specifically recommend rituximab at 500 or 1,000 mg, given by intravenous infusion every six months for two years. No study has directly compared these two dosages in terms of efficacy or safety, highlighting another avenue for further research.
Additionally, there is a paucity of data on rituximab maintenance therapy for over two years. The guidelines suggest that therapy could be extended to five years in people with high relapse risk, but more research is needed to understand the effects of extended rituximab maintenance therapy.
Broadly, these guidelines stress that treatment needs to be individualized, particularly for people who might be more sensitive to its side effects, such as those with other disorders (comorbidities) and the elderly. Individualized treatment is similarly stressed for people who experience a relapse while on rituximab therapy; the guidelines recommend referral to a specialized care center that takes into account the patient’s specific situation.
Treatment with other disease modifying anti-rheumatic drugs — including azathioprine, methotrexate, and mycophenolate — should be stopped when starting rituximab maintenance therapy in order to minimize side effects, the guidelines recommend. Glucocorticoids should be weaned off over the course of six to 12 months when starting rituximab maintenance therapy, though this withdrawal may be more challenging in people with EGPA than the other two disease subtypes.
The guidelines suggest preventive treatment against Pneumocystis jirovecii, a pneumonia-causing fungus, in individuals on rituximab. They also stress the importance of appropriate vaccinations (e.g., flu shots). Ideally, vaccines should be given at least a month before starting rituximab, though “timing should not preclude vaccination,” the team wrote.
In people on rituximab maintenance therapy, the guidelines highlight the importance of routine monitoring for side effects, particularly hypogammaglobulinaemia (low antibody levels) and neutropenia (low levels of neutrophils, a type of immune cell), both of which can increase the risk of infection. Further research is needed to identify the optimal way to manage these side effects when they do develop in people with AAV on rituximab.
Additional areas where further research is needed include how maintenance therapy affects quality of life, the economic impact of this therapy, and the use of rituximab maintenance therapy in special populations, such as children and pregnant people.
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