The maintenance of remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, who have kept their autoantibodies under control after at least two years of rituximab therapy, has proven to be a challenge. However, a team of nephrologists in Boston has reported that a longer-term strategy is being implemented. A rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies for reducing the risk of relapse.
„The bottom line is, using the B-cell strategy, which involved re-dosing rituximab when B-cells recovered or began to recover, we have a relapse rate of only 6% after 3 years,“ said lead study author John L. Niles. MD, Assistant Professor of Medicine at Harvard Medical School and Director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape.
„While we waited for serologic relapse and hoped we could prevent clinical relapses with the other strategy, we still had a relapse rate of about 30% after three years,“ he said.
Niles and his team reported their findings from the MAINTANCVAS study (MAINTenance of ANCA VASculitis) on December 11, 2023 in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after at least two years of rituximab therapy with a fixed schedule: an approach where rituximab was re-infused after B-cell repopulation, called the B-cell arm, and a strategy where rituximab was re-infused when serological ANCA levels significantly increased, termed the ANCA arm. A total of 115 patients were randomized to one of the two arms.
The mean follow-up time was 4.1 years from the start of the study. During the entire study, there were relapses in 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm. According to Kaplan-Meier analysis, 3 years after the start of the study, 4.1% of patients in the B-cell arm experienced a relapse compared to 20.5% of patients in the ANCA arm. After 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, there were four severe relapses in the B-cell arm and seven in the ANCA arm.
The COVID-19 pandemic led the researchers to terminate the study before it was fully recruited, Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in this study population. The total number of SAEs was identical in both arms: 22 (P = .95). However, there were six cases of COVID-19 in the B-cell arm, compared to one in the ANCA arm, including two deaths due to COVID-19.
The study provided insights into how the treatment can be best individualized for patients with ANCA-associated vasculitis, Niles said. „We typically start with the B-cell strategy after two years, but as people have infections or hypogammaglobulinemia, we start taking the B-cells for longer, and if the value with respect to infection is high, we will stop and switch to the ANCA strategy,“ he said.
He added, „Relapsed patients get a stricter B-cell strategy, and people with infections get much longer intervals or even switch to the ANCA strategy.“
Since the study ended before full recruitment was completed, it was inadequate for subgroup analyses, Niles noted. One such potential subgroup was recurrent patients with interstitial lung disease as the primary clinical finding. „Interstitial lung disease does not seem to respond as well to therapy as the other classic features of ANCA disease,“ Niles said. „It’s the one part that is perhaps the most problematic in the long run. It behaves differently and will need more research into ILD. Fortunately, it’s a relatively small percentage of the overall group, but it is the most difficult part.“
Insights in Context
„This study brings clarity to how patients with ANCA-associated vasculitis can be best treated,“ said Dr. Robert Hylland, Clinical Assistant Professor of Rheumatology at Michigan State University College of Osteopathic Medicine.
„Most of us have been trying to figure out from the existing literature how to deal with [ANCA-associated vasculitis]. There have been a number of different approaches that have changed over time,“ said Hylland. „But this article now helps us understand how to manage this disease after we have achieved remission. The ability to determine the validity of serology compared to B-cell depletion was very nicely highlighted in this article.“
The size of the study population is a strength of the study, according to Hylland.
He praised the study authors for providing insights into the use of positive myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA values as a guide for treating relapses. The study defined a serological ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold increase in PR3.
„Many of us would not have recognized that, for example, an increase in MPO less than fivefold could be observed for a while, while most of us would have treated that serologic flare,“ Hylland said.
The study also highlighted the difficulty of assessing a patient who has neither positive ANCA nor a significant increase in their B-cell numbers and yet presents with clinical signs and symptoms of relapse, for example, in granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.
„Many physicians tend to be somewhat more relaxed when they see that their patient is doing well serologically, and yet some of the subtle symptoms of Wegener’s syndrome could be overlooked when treating it, if you don’t recognize that there are a considerable number of people who come to you with treatment and still have a negative serology,“ Hylland said.
The study did not have a specific external funding source. Niles and Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.
Richard Mark Kirkner is a medical journalist based in the Philadelphia area.