Relative Benefits, Risks of AAV Induction and Maintenance Therapies Reviewed

The antibody rituximab is a good alternative to cyclophosphamide for inducing remission in people with ANCA-associated vasculitis (AAV), and is better than azathioprine as a maintenance therapy, researchers reported.

These were among the findings from a recent review study that investigated the relative benefits and risks associated with different treatment regimes for AAV patients.

The study, “Granulomatosis With Polyangiitis and Microscopic Polyangiitis: A Systematic Review and Meta‐Analysis of Benefits and Harms of Common Treatments,” was published in ACR Open Rheumatology.

There are several approved treatments for AAV, which generally aim to reduce the activity of the immune system. Typically, patients start with an induction treatment (higher doses of medication to initiate disease remission) followed by maintenance therapy (lower doses over time to maintain remission).

Understanding the relative benefits and risks of different treatment regimens is an ongoing area of study.

A team of researchers in the U.S. conducted a review of the existing scientific literature on treatments for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two most common forms of AAV. In total, the researchers reviewed 729 previously published studies.

Common strategies for induction treatment include immune-suppressing steroids (glucocorticoids) given in combination with another immunosuppressive agent, such as cyclophosphamide or rituximab. Data from various studies did not indicate any significant difference between cyclophosphamide and rituximab in terms of inducing remission.

Of note, differences were found for cyclophosphamide based on its route of administration: compared to oral cyclophosphamide, intravenous (into-the-bloodstream) cyclophosphamide is associated with a greater frequency of relapses, but a lower likelihood of severe leukopenia (abnormally low white blood cell levels).

“The decision about the route of CYC [cyclophosphamide] administration should be made on an individual basis,” the researchers wrote.

Some data indicated that plasma exchange as part of induction therapy could lessen the extent of kidney disease, particularly in individuals at high risk of severe kidney disease. However, plasma exchange didn’t have a clear effect on mortality or remission rates, and some studies reported conflicting results.

The researchers speculated that this could be due to the advent of new therapies that diminish the potential benefit of plasma exchange, leading to benefits in some studies but not others, depending on treatment combination used.

Maintenance therapies for AAV include methotrexate, azathioprine, and mycophenolate mofetil (MMF), as well as cyclophosphamide and rituximab (given at lower doses than for induction therapy).

Data indicated no substantial differences, in terms of relapses or toxicities, between methotrexate and azathioprine.

One study comparing azathioprine to MMF found MMF to be associated with a higher rate of relapses, without notable differences in toxicities.

Another maintenance regime, called trimethoprim/sulfamethoxazole (T/S), was more effective than a placebo at inducing remission in multiple studies. One that compared T/S to methotrexate found linked methotrexate with a lower rate of relapses, but also with a higher incidence of adverse events.

Comparisons between rituximab and azathioprine generally favored rituximab in terms of preventing relapses and extending survival. However, data were not clear on the optimal regime for rituximab as a maintenance therapy.

“Currently, there is not enough evidence to evaluate the most effective maintenance regimen after RTX [rituximab] induction,” the researchers wrote.

Some trials that investigated azathioprine as a maintenance treatment showed that a longer treatment duration — four years, as compared to two or less — was associated with a lower risk of relapses, without any notable differences in toxicities. The researchers noted a need for further studies on the optimal length of maintenance therapies.

Of note, most of the included studies were relatively weak in a statistical sense — mathematically, studies with more participants are better able to identify statistically meaningful differences. The researchers suggested that this weakness reflected the difficulty of conducting studies in a rare disease like AAV.