French Investigators Report Rituximab Immunogenicity Findings

Tony Hagen

Tony Hagen is senior managing editor for The Center for Biosimilars®.

Immunogenicity was rare but concerning for patients who switched from originator rituximab to the biosimilar Riximyo, investigators reported.

Investigators have reported a rare incidence of immunogenicity “with possible clinical and biological consequences” for patients treated with biosimilar rituximab (Riximyo, GP2013).

Investigators at the Rheumatology Department of Cochin Hospital, Paris, France, enrolled 159 patients who were treated with GP2013 (Riximyo; Sandoz) since March 2018 and included those who were previously treated with originator rituximab (RTX). The biosimilar is marketed in Canada and the European Union, but not in the United States.

Patients had rheumatoid arthritis (RA; n = 108), systemic sclerosis (SSc; n = 16), mixed connective tissue disease (MCTD; n = 15), and various other conditions in smaller proportions. The investigators said 25% of patients overall were RTX naive, and 75% were in maintenance therapy with RTX prior to switching to the biosimilar in March 2018.

Patients were tested for antidrug antibodies (ADAs) and residual rituximab concentrations. In the initial analysis, prior to the second GP2013 infusion, findings showed 8 patients (5%) positive for antidrug antibodies (RA, 5; MCTD, 1; SSc, 1; systemic lupus erythematosus [SLE], 1).

ADA rates were from 6 to greater than 100 ng/mL and “were associated with undetectable residual rituximab concentrations.” Among the 8 patients positive for ADAs, 6 had previously received RTX and 2 were RTX naive.

Investigators reported a trend toward higher mean (SD) body mass index for patients testing positive for ADAs (28 [7] vs 25 [6] kg/m2; P = .12). They reported no associations between RTX immunization and age, disease duration, combination with conventional disease-modifying antirheumatic drugs, mean interval between infusions, or cumulative originator rituximab dose.

In stratification, the investigators reported 3 patients with high ADA levels (≥100 ng/mL), including 2 with RA and 1 with MCTD; decreased efficacy for 2 patients; incomplete B-cell depletion; RTX dose escalation from 500 mg to 1 g; and 1 severe allergic reaction.

Among 5 patients with mild ADA levels (6-22 ng/mL), the investigators reported 3 with RA, 1 with SLE, and 1 with SSc. Treatment was continued in all 5 cases with no loss of efficacy within an average of 13 months of follow-up. One minor allergic reaction was reported.

“The immunogenicity of patients treated with rituximab is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels,” the investigators concluded.

Reference

Avouac J, Cougnaud Murail R, Goulvestre C, et al. Immunogenicity of rituximab biosimilar GP2013: a rare event, but not without consequences… Presented at: EULAR 2021; June 2-5, 2021. Poster 0600.