Background/Purpose:  Development of biosimilar monoclonal antibodies should not be limited by evaluation of quality, efficacy and safety in comparison with innovator biological product. Interchangeability assessment may have a major impact on biosimilar use in routine practice.

Methods:  160 adults (18-80 y. o.) with active seropositive rheumatoid arthritis (RA) diagnosed by ACR 1987 criteria who did not respond to 1 or more TNF-inhibitors were included in Russia, Ukraine, Belarus and India. After the screening, patients were randomized (1:1) into 2 arms: in the main arm BCD-020 (rituximab biosimilar, JSC BIOCAD, Russia) was dosed at 1000 mg IV on day 1 and 15; in the reference arm innovator rituximab (F.Hoffmann-La Roche, Ltd., Switzerland) was administered using the same regimen. After 6 months patients with active RA were treated repeatedly with partial crossover: half of patients from the main arm received BCD-020, whereas the second half was treated with innovator rituximab (arms BB and BR, respectively). The same was done in patients with active RA from the reference arm (arms RR and RB, respectively). Both periods of treatment (0-24 weeks, 24-48 weeks) were conducted in double-blind manner.

Results:  efficacy after the first course of treatment in both arms was equal: at 24 weeks of the treatment ACR20 was reached in 84.14% of patients from the main arm and in 87.01% of patients in the reference arm (95% CI [-13.95%; 8.74%], p=0.773). There were no significant differences after partial crossover at 48 weeks: ACR20 was obtained in 77.78% and 92.31% of patients in RB and RR arms (p=0.250), and in 96.00% and 89.29% in BB and BR arms (p=0.613). Similar data were observed when other efficacy endpoints were compared (remission by DAS28, low activity by DAS28, ACR/EULAR2011 remission etc.). In all arms high rate of ACR70 at week 48 was reached: 40.0% of patients in BB arm, 34,62% in RR arm, 40.74% in RB arm and 39.29% in BR arm. In total, during the first 6 months of treatment AEs were registered in 59.34% and 54.12% of patients in the main and reference arms, respectively, with 2 SAEs in reference arm (myocardial infarction and lung thromboembolism, possibly related). There were no differences in rates of AEs in the switched arms: 44.44% in BB arm, 38.46% in RR arm, 57,14% in RB arm and 62.50% in BR arm, with 1 SAE in BB arm (death due to car accident, unrelated). Incidence of binding antibodies to rituximab was 3.57% and 8.75% in the main and reference arms, respectively (0-24 weeks), and 3.85% in BB arm (24-48 weeks; no binding antibodies in other groups).

Conclusion:  BCD-020 is highly similar to innovator rituximab in terms of efficacy, safety and immunogenicity. 1-year data show that switching between products does not affect treatment outcomes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interchangeability-of-innovator-rituximab-and-its-biosimilar-results-from-international-controlled-comparative-1-year-study-in-patients-with-active-rheumatoid-arthritis/