Impaired Kidney Function Associated with Increased Risk of Side Effects in Patients with Small Vessel Vasculitis Treated with Rituximab as an Induction Therapy

Abstract

Rituximab (RTX), a monoclonal antibody against the CD20 molecule, is used as an induction therapy in the treatment of small vessel vasculitis (SVV). The aim of the study was to evaluate the efficacy and safety of RTX induction therapy for refractory SVV. A retrospective analysis of 20 patients treated with RTX for active SVV (BVAS/WG ≥ 3) was performed to assess the remission rate and the drug-related severe adverse events 6 months after therapy. The mean age of the studied population was 49 ± 13 years (50% female), 90% of which were PR3-ANCA positive. Complete remission was achieved in 85% of patients, and partial remission was achieved in a further 10% within 6 months after RTX infusions. The remission rate was not influenced by kidney function. Adverse events such as infections (25%), a late onset of neutropenia (10%) and severe hypogammaglobulinemia (5%) were noted. The patients who developed adverse events were older (42 ± 11 vs. 57 ± 12 years; p = 0.014) and had a higher serum creatinine level (1.3 mg/dL vs. 3.35 mg/dL; p = 0.044). Patients with a glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2 had a nine-fold higher risk of side effects (OR 9.0, 95%CI: 1.14–71.0). In conclusion, RTX was highly effective as an induction therapy in patients with SVV. Advanced kidney failure with an eGFR lower than 30 mL/min/1.73 m2 was one of the risk factors for the occurrence of side effects.

The Efficacy and Safety of Rituximab in ANCA-Associated Vasculitis: A Systematic Review

“…RTX was thought to be an effective induction treatment in small vessel vasculitis, mainly in GPA patients [ 115 ]. Complete remission was reached more frequently in GPA patients than in MPO [ 116 ].…”

“…It was reported that hypogammaglobulinemia was more frequent within the first six months of RTX therapy [ 213 ]. The incidence of hypogammaglobulinemia and its severe form was reported to be about 50% [ 214 ] and 5% of patients, respectively [ 115 , 213 , 215 ]. However, the incidence of hypogammaglobulinemia varied according to the indication for RTX, whereas it was observed in 46% of pediatric lupus, 71% of autoimmune CNS disease, 60% of ANCA-associate vasculitis patients, and 12% in miscellaneous groups [ 213 ].…”

“…The infection rate of AAV patients following RTX therapy was higher than RA, which is related to the systemic nature of AAV, damage to the airways that predisposed the airway to infection, and long-term specific IS drugs used for AAV [ 226 ]. It seems that some risk factors exist that increase the risk of infection, including old age [ 115 , 224 ], low body mass index [ 214 ], bronchiectasis, endobronchial involvement [ 227 ], kidney dysfunction [ 214 , 225 ], and nephritic disease treated with GC-RTX [ 214 ], which is a risks factor for other side effects as well as infection [ 115 ]. It was shown that using trimethoprim-sulfamethoxazole prophylaxis reduced the risk of infection [ 227 ].…”

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series

“…The mechanism of RTX in AAV is is not entirely known, but it likely depletes B cells and plasmablasts producing ANCA. However, severe infections were not rare in patients on recommended doses such as four weekly pulses of 375 mg/m 2 or 1 g twice monthly [14], especially in Chinese patients [2,16]. Among 27 Chinese AAV patients receiving a mean RTX dose of only 1270 mg, the severe infection rate during the follow-up period of 23.6 ± 14.0 months was 37%, corresponding to an event rate of 20.9 per 100 personyears [2].…”

“…RTX is a chimeric monoclonal antibody that targets the antigen CD20 on the surface of B cells and clears B cells from the circulation. Compared with traditional immunosuppressive agents, RTX has fewer side effects, including infusion reactions, late-onset neutropenia, and infection [14]. The frequency of infections is related to the cumulative dose of immunosuppressants, concomitant diabetes, and impaired kidney function [15].…”