Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database

Mult Scler. 2021 Jun;27(7):1066-1076. doi: 10.1177/1352458520949986. Epub 2020 Aug 21.


Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.

Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug-AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1.

Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug-AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively).

Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.

Keywords: CD20; FAERS; Rituximab; adverse event profile; multiple sclerosis; ocrelizumab.

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Antibodies, Monoclonal, Humanized
  • Drug-Related Side Effects and Adverse Reactions* / epidemiology
  • Humans
  • Pharmacovigilance*
  • Rituximab / adverse effects
  • United States / epidemiology
  • United States Food and Drug Administration


  • Antibodies, Monoclonal, Humanized
  • Rituximab
  • ocrelizumab