Comparative Safety and Effectiveness of Biosimilar and Originator Rituximab for Induction or Maintenance in ANCA-Associated Vasculitis: 6-Month Results of a Longitudinal Cohort Study

Objectives To evaluate the effectiveness and safety of rituximab biosimilars compared to the originator in Canadians with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and outcomes following originator to biosimilar switching. Methods We recruited adults with GPA or MPA who started rituximab originator or biosimilar for induction or maintenance or switched from originator to biosimilar maintenance between 01/2018-09/2023. Eligible participants either started the index treatment in the prior 6 months or were followed within an existing vasculitis cohort. Six-month outcomes include remission (Birmingham Vasculitis Activity Score [BVAS] v3 of 0), relapse (rise in BVAS after achieving remission, requiring treatment), change in Vasculitis Damage Index (VDI), and serious adverse events (SAEs). Results We enrolled 200 participants from 9 centers: 126 who started induction (52 originator, 74 biosimilar), 58 who started maintenance (22 originator, 36 biosimilar), and 16 who switched from originator to biosimilar maintenance (median 2 years [IQR 1.4-2.2] of originator maintenance prior to switching). Mean age was 57.1 (SD 17.4), 53% were female, 79% White, and 69% had GPA. Baseline characteristics across subgroups are reported in Table 1. 190 (95%) participants had follow-up visits at Month 6 or died prior to this visit. Over a mean follow-up 189 days [SD 56], 2 minor relapses occurred in PR3-ANCA+ individuals, one in the biosimilar induction subgroup (10 weeks), and one in the originator maintenance group (at 4 months). Among induction recipients, 48/49 (98%) in the originator group and 66/71 (93%) in the biosimilar group were in remission at Month 6. All in the originator and biosimilar maintenance subgroups were in remission at Month 6, and all 16 who switched from originator to biosimilar maintenance remained in remission during follow-up. Mean change in VDI was similar between biosimilar and originator subgroups. One or more SAEs occurred in 4/49 (8%) of the originator induction subgroup, 11/71 (15%) of the biosimilar induction subgroup, 2/21 (10%) originator maintenance subgroup, 2/33 (6%) of the biosimilar maintenance group, and 3 (19%) of the ‘switch’ group. Two deaths occurred in the biosimilar induction subgroup (1 alveolar hemorrhage, 1 COVID-19) and 1 death occurred in the switch group (infection, 5.5 months after switching). Table 1. Baseline cohort characteristics at time of starting rituximab originator, biosimilar, or switching from originator to biosimilar (N=200) 1 Conclusion In this cohort, we did not observe differences in remission or relapses at 6 months between RTX originator or biosimilar induction or maintenance. Disease remained stable in those who switched from originator to biosimilar maintenance. Supported by a CIORA grant