1 in 4 patients may relapse on rituximab maintenance, study finds
Kidney involvement among factors tied to lower relapse risk
About a quarter of people with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) under maintenance treatment with rituximab experience relapses, mainly during the first two years.
That’s according to a real-world study in Greece that looked at data from 101 people with GPA or MPA, the two most common types of ANCA-associated vasculitis (AAV).
Data also showed that kidney involvement, induction treatment with rituximab plus cyclophosphamide versus rituximab alone, and earlier complete remission after induction treatment were significantly associated with a lower risk of relapse.
“Our findings support the efficacy and safety of [rituximab] as a long-term maintenance agent for GPA/MPA patients after complete-remission,” the researchers wrote.
The study, “Relapses and serious adverse events during rituximab maintenance therapy in ANCA-associated vasculitis: a multicentre retrospective study,” was published in Rheumatology.
Relapsing during maintenance therapy
AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels in several organs, leading to the disease’s symptoms. Most cases are triggered by self-reactive antibodies called ANCAs.
Current available treatments aim to induce and maintain disease remission. Still, “up to 50% of AAV patients will relapse even during maintenance therapy,” the researchers wrote.
Rituximab (sold as Rituxan, among others, with biosimilars available) is an approved induction and maintenance treatment for AAV. The therapy works to reduce the levels of B-cells, the immune cells that produce antibodies, including ANCAs.
However, “real-life data assessing the efficacy and safety of RTX [rituximab] maintenance therapy are limited,” the researchers wrote.
The team set out to assess the relapse rate and risk factors of relapses in 101 GPA and MPA patients treated with rituximab maintenance regimen at four clinics. All had achieved complete remission with induction regimens and were followed for at least six months after starting rituximab maintenance treatment.
Remission was defined as a Birmingham vasculitis activity score (BVAS) of zero, meaning no disease activity, plus a dose of the glucocorticoid prednisolone or equivalent of up to 7.5 mg/day. Higher BVAS values indicate more severe disease.
Fifty-two percent of the patients were male, 69% had GPA, and 93% were positive for ANCAs. The most commonly affected organs were the lungs, for 61% of patients, and the kidneys, for 55%.
Disease remission has been induced with glucocorticoids, together with rituximab (64%), cyclophosphamide (10%), or a combination of rituximab and cyclophosphamide (21%).
Rituximab maintenance therapy, given once every six months, was initiated at a median age of 63, and a median of seven months after induction treatment. Patients received a median of three rituximab cycles, at doses ranging from 500 mg to 2,000 mg per cycle, over a median follow-up period of nearly 1.5 years. Follow-up time ranged from about six months to three years.
Overall, 24% of patients experienced a total of 30 relapses during follow-up, with 73% of relapses occurring during the first two years after initiating maintenance treatment.
The relapse rate was 41.8 per 100 patient years within the first year. One hundred patient years refers to data gathered from 100 patients who were followed for one year. In the second year, the rate was 15.6 per 100 patient years, and in the third year it was 3.7 per 100 patient years.
Fifty-seven percent of the relapses were considered major, and 53% involved the lungs. These cases were mostly managed with a rituximab re-induction regimen, with a complete remission rate of 73%.
Minor relapses were reported in 11 patients, with 77% involving joint pain and inflammation. These were more frequently managed by adding either glucocorticoids or methotrexate to rituximab maintenance regimen, but four patients remained on rituximab alone without subsequent relapses.
Statistical analyses showed that several factors at treatment start were significantly associated with a lower risk of relapse during rituximab maintenance treatment.
Kidney involvement tied to lower relapse risk
Kidney involvement was linked to an 80% lower relapse risk, which is consistent with previous findings, the team noted. While the link could be due to this type of patients receiving more aggressive treatment, in the current study, the association was observed “independently of the induction treatment received,” the researchers wrote.
Induction treatment with rituximab plus cyclophosphamide was found to significantly reduce relapse risk — by 98% — compared with rituximab alone.
And the risk of relapse increased by 7% for each month passed between induction treatment start and the moment of complete remission, meaning that a faster remission was associated with a lower relapse risk.
When looking at major relapses alone, the team found that only kidney involvement was significantly associated with a reduced risk, by 90%.
Also, 14 patients (41%) experienced a total of 17 serious infections, corresponding to 5.8 infections per 100 patient years. These more commonly affected the respiratory tract (41%), and mainly occurred within the first year of maintenance treatment.
Among other reported serious adverse events, the most common were hospitalizations due to COVID-19, occurring in 11 patients (10.9%).
A total of 10 patients died (10%), mainly due to infections.
“Our study showed that in real-life RTX-maintenance therapy was efficacious with relapses occurring in approximately one quarter of patients,” the researchers wrote. However, they added, serious infections “remain a concern,” being “the leading cause of death.”
There is a “need for close monitoring and strategies to prevent infectious complications,” they concluded.
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