Real-world use of MabThera (rituximab) as an induction treatment for patients with ANCA-associated vasculitis (AAV) on low-dose prednisone led to successful complete remission rates that matched those seen in a key clinical trial, according to a study.
However, the investigators believe that the increasing number of relapses after treatment with Mabthera (marketed as Rituxan in the U.S.) warrants the need to enhance maintenance treatment for patients.
The study, “Rituximab prescription patterns and efficacy in the induction treatment of ANCA-Associated Vasculitis in a Belgian multicenter cohort,” appeared in the journal Acta Clinica Belgica.
Cyclophosphamide and glucocorticoids have long been the standard option for remission induction in patients with AAV. However, frequent relapses and severe disease flares required extended treatments associated with severe side effects, prompting the development of new therapies.
The Phase 2/3 RAVE trial (NCT00104299) compared Rituxan to cyclophosphamide for the induction of complete remission in 197 patients with severe AAV. It showed that a similar proportion of patients receiving 375 mg/m² Rituxan once weekly for four weeks had complete remission compared with a group on cyclophosphamide (2 mg/kg per day).
Although no differences between groups were found in the overall population, with or without prednisone, Rituxan (marketed by Genentech and Biogen) significantly outperformed cyclophosphamide in patients with relapsing disease. These benefits led to the approval of Rituxan in the U.S. and Europe for the induction of remission in AAV.
In Belgium, treatment with MabThera (developed by Roche, which owns Genentech) has been reimbursed since 2014. A research team at four Belgian university-affiliated hospitals conducted a retrospective analysis to assess the modalities of reimbursement, prescription, and efficacy of MabThera in AAV induction treatment.
The study included 57 patients, with a mean age of 57 years, who received MabThera between May 2014 and June 2017. Most (84%) had granulomatosis with polyangiitis (GPA), and the remaining 16% had microscopic polyangiitis (MPA).
MabThera was reimbursed for induction treatment after relapse on cyclophosphamide (54.4%); in situations where cyclophosphamide was not recommended (38.6%), most commonly in women of childbearing age (28.6%) and those with bladder inflammation or carcinoma (23.8%); and for patients not responding to cyclophosphamide (26.3%).
MabThera was prescribed mostly by internists (73.7%), followed by rheumatologists (17.5%), and nephrologists (8.8%). The dosing regimen used in RAVE — 375 mg/m² once weekly for four weeks — was prescribed most often (88%).
Organ involvement was most frequent in the lungs (68.4%). Severe disease, typically acute kidney injury, was observed in 30% of patients, as assessed with the Birmingham Vasculitis Activity Score-WG.
In patients who relapsed after successful induction treatment with MabThera, 66.7% received a new dose of the therapy, 16.7% received higher doses of corticoids, 8.3% were given methotrexate, and 8.3% did not receive any additional treatment.
Three patients experienced serious adverse events upon treatment with MabThera — a skin allergy after the first infusion, a coronary vasospasm (sudden blood vessel tightening), and a severe acute infectious pneumonia one week after infusion.
Use of low-dose prednisone (less than 10 mg) enabled higher complete remission rates throughout 24 months than no use of this corticosteroid — 66.7% vs. 0% at six months, 57.4% vs. 4.2% at 12 months, 40% vs. 2.5% at 18 months, and 25% vs. 2.8% at 24 months.
The complete remission relapse rate in people not taking steroids was inferior to that from RAVE, which the investigators attributed to the earlier withdrawal (at six months) of prednisone in patients achieving remission in the trial.
Antibody levels decreased significantly at six months, but started to increase again at 12 months. A similar trend was found with the levels of CD19, biomarker of immune B-cells.
The relapse rate was 13.6% after six months, 22.7% between six and 12 months, 27.3% between 12 and 18 months and 31.8 % between 18 and 24 months 18. In patients with severe disease, the relapse rate was 14% at six months, 21% between six and 12 months, 25% between 12 and 18 months, and 35.7 % between 18 and 24 months.
In the total group, the cumulative relapse rate at 24 months was 59.4%, and the mean relapse time was 16 months. Relapse rate increased slowly and reached a maximum between 18 and 24 months in both total and severe disease groups.
Type of organ involvement, disease or antibody type, and reimbursement criteria did not affect remission or relapse rates. However, including more patients followed by nephrologists and presenting severe renal involvement may have influenced the results.
“Our results confirm those of RAVE regarding complete remission rates with (low-dose) prednisone,” the scientists wrote. “The high prevalence of relapses — especially after 18 months — underlines the need to optimize maintenance treatment after an induction treatment with [MabThera/Rituxan],” the researchers said.