People with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis have a lesser chance of relapse if they continue with maintenance treatment for two years instead of one, according to the results of a clinical trial.
The trial, led by researchers at the Hôpital Européen Georges-Pompidou in France, also showed that patients who stayed on maintenance treatment with azathioprine and prednisolone for longer had a lower risk of end stage kidney disease.
The study, “Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis,” was published in the journal Annals of the Rheumatic Diseases.
This inflammatory disease that commonly affects the kidneys is usually treated in two stages. An induction treatment — most often with cyclophosphamide or Rituxan (rituximab) in combination with high-dose glucocorticoids and sometimes plasma exchanges — aims to induce remission of the disease.
Induction is then followed by maintenance treatment, usually with oral immunosuppressive therapies such as azathioprine, methotrexate, or Rituxan, either with or without low-dose glucocorticoids.
Despite maintenance treatment, 30–50% of patients relapse within five years. There is also no guidance on the optimal duration of maintenance treatment to lower relapse risks.
To understand if longer maintenance treatment better protects against relapse, the European Vasculitis Society sponsored a clinical trial (ISRCTN13739474) comparing the benefits of maintenance treatment with azathioprine and prednisolone, continuing until 24 or 48 months after diagnosis.
The trial enrolled 117 patients already in remission, randomized to receive either longer or shorter maintenance treatment. Among them, 53% had ANCA antibodies.
The difference in the length of maintenance treatment led to significant differences in relapse rates: 62.7% of patients in the group that stopped treatment after 24 months had a relapse, compared with 22% in the group that continued for 48 months. This translated to a 2.84-fold higher risk of relapse with early treatment discontinuation.
Patients who continued with treatment also lived longer before they experienced the first relapse.
While patients who continued treatment for 48 months slightly improved their kidney function during the trial, those who quit early had a poorer kidney function by the end, compared with the start of the trial. Among them, four patients developed end-stage kidney disease, compared with none in the continuation group.
Patients who stopped treatment early also saw the ANCA antibodies reappear to a larger extent. At the beginning of the trial, 56% in the early termination group tested positive for ANCA. By month six, 72% had ANCA antibodies. In the continuation group there was no difference, with 51% and 52% of patients having antibodies on the two occasions, respectively.
Analyses showed that the only factors that could predict a relapse were early withdrawal from treatment and the presence of ANCA at the start of the study.
The better outcomes in the continuation group, however, came at a cost. Those who continued experienced more adverse events than those who didn’t — 43 compared to 28. Also, severe adverse events were more frequent in the long-term treatment group, with nine patients having a severe adverse event compared to only three in the discontinuation group. Particularly, blood abnormalities and cardiovascular events were more common.