Long-term remission is higher with an 18-month fixed rituximab regimen compared with azathioprine or 18-month tailored rituximab.
Introduction
ANCA-associated vasculitis (shortened to AAV), is a rare group of diseases of the immune system. These diseases are linked to a type of autoantibody called ANCA. An antibody is a protein that the normal healthy immune system makes to attack foreign substances in the body, such as viruses or bacteria. In people with AAV the body makes antibodies that attack its own tissues – these are called autoantibodies. In AAV, the ANCA autoantibodies cause damage to small blood vessels. Any part of the body can be affected, but AAV most often affects a person’s kidneys, lungs, joints, nerves, and may cause bleeding in their nose and ears. AAV is very severe, and can be life-threatening if left untreated.
Azathioprine has been used for many years to keep AAV in remission. Remission means that the disease is under control, and there are no signs of symptoms of active disease. Rituximab is another type of drug that is used in several autoimmune diseases, and which could also be useful in people with AAV. Rituximab is one of a group of medicines called biologics (sometimes also called bDMARDs). It works by targeting B cells, a type of white blood cell, which produce ANCA antibodies.
What did the authors hope to find?
The authors wanted to work out the optimal schedule and duration of rituximab to be used as maintenance therapy in people with AAV.
Who was studied?
The study included 277 people over the age of 18 years with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Everybody taking part was in complete remission after having a course of induction therapy.
How was the study conducted?
This was a pooled, long-term analysis of three clinical trials. The first compared an 18-month fixed-schedule rituximab versus azathioprine (the MAINRITSAN study). The second looked at an 18-month fixed-schedule of rituximab versus 18-month tailored rituximab (MAINRITSAN2). In this second trial, tailored meant that rather than using rituximab at fixed intervals it was given on demand, or as needed in relation to each person’s disease activity. In the third trial, therapy was extended to 36 months, with people from MAINRITSAN2 getting four additional rituximab infusions or placebo (MAINRITSAN3). Everyone was then followed until 84 months, and the data pooled to look at whether people had experienced AAV relapses, or had any side effects.
What were the main findings of the study?
The main finding was that 18-month fixed-schedule rituximab was superior to azathioprine in preventing major relapses at Month 84.
Additionally, the 18-month tailored rituximab regimen was associated with an increased risk of major relapse compared to fixed-schedule regimen. But the risk of major relapse was similar between people who had fixed schedule rituximab for 18 or 36 months. Because of this, the authors think that extending rituximab from 18 to 36 months should be considered only in patients at high risk of relapse.
In light of these long-term findings, 18-month tailored rituximab regimens should no longer be recommended as they are associated with an increased risk of major relapse. Instead, a fixed-schedule regimen of at least 18 months should be considered the gold standard.
Are these findings new?
Yes and no. These findings are based on pooled data from previous trials. But this study is the largest cohort of patients evaluating different rituximab maintenance regimens in GPA and MPA. The MAINRITSAN2 trial concluded that there was no significant difference in relapse rates after 28 months between the 18-month tailored RTX regimen and the 18-month fixed-schedule RTX regimen; however, now the results are different and therefore new.
What are the limitations of this study?
A key limitation is that the original studies were not designed for these comparisons, and some of them may be underpowered. In addition, the comparison of different study populations may have biased the analysis, but the authors say they controlled for this by adjusting for identified prognostic factors. Finally, there was a bias introduced by including only non-relapse patients from MAINRITSAN2, but the authors controlled for this in the data.
What do the authors plan on doing with this information?
In light of these results, azathioprine and 18-month tailored rituximab regimens should no longer be recommended for the majority of patients, and a fixed-schedule rituximab regimen of at least 18 months should be the gold standard. Further studies will be considered to look into whether there is a need for personalised extension therapy based on factors that predict an individual’s risk of relapse.
What does this mean for me?
If you have GPA or MPA and are in complete remission after induction therapy, you should benefit from 18 months of fixed-schedule rituximab maintenance therapy. This is preferable to 18 months of tailored rituximab, since the fixed schedule results in a lower risk of relapse. This change could also make your treatment regimen easier, which might improve your quality of life.
If you have any concerns about your disease or its treatment, you should talk to your doctor or a healthcare professional involved in your care.
Date prepared: July 2024
Summary based on research article published on: January 2024
From: Summary from Delestre F, et al. Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials. Ann Rheum Dis 2024;83:233–41. doi:10.1136/ard-2023-224623
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