High efficacy therapies, including anti-CD20 monoclonal antibodies (CD20Mabs), are increasingly used and recommended for people with multiple sclerosis (pwMS) due to an accumulation of data demonstrating superior efficacy in reducing relapses, MRI lesions and disability accrual. ^{Reference Freedman, Clift and Devonshire1} While low attrition rates were seen in pivotal trials, ^{Reference Hauser, Kappos and Arnold2} real-world evidence on discontinuation of CD20Mabs is understudied, particularly in the Canadian landscape.

The current paper by Hunt et al. ^{Reference Hunt, Chu and Kuipers3} is a retrospective exploration on discontinuation of ocrelizumab and rituximab in two British Columbia MS clinics. British Columbia is unique in Canada whereby provincial access for CD20Mabs preferentially covers off-label rituximab as a first-line CD20Mab. Ofatumumab, the other of the two on-label CD20Mabs available in Canada, was not studied as it came to market in 2021, halfway through study enrollment dates.

Effectiveness of a therapy is driven by adherence rate. Reassuringly, overall low rates of discontinuation were found, with only 141 of 881 (16%) participants stopping CD20Mabs after a cumulative 2337 patient-years. Rates of discontinuation were not different at 36 months between ocrelizumab and rituximab (12.5% vs. 22.2%, p = 0.46). However, those on rituximab had a shorter median time to discontinuation than ocrelizumab (11.5 vs 21.0 months, p < 0.0001). Although the study was not designed to assess why pwMS discontinued rituximab earlier, the authors suggested possible factors, including its mouse-chimeric design and potential for more drug antibodies. ^{Reference Dunn, Juto and Ryner4}

Conversely, no difference in the reasons for discontinuation was found, with infusion reactions being the most cited in both groups. Infections were the next most common cause for discontinuation, noting that this study captured the beginning of the COVID pandemic. New disease activity occurred in only 16 of 881 (1.8%). Interestingly, lapse in insurance coverage accounted for more discontinuation than did breakthrough inflammatory disease.

This paper reinforces that CD20Mabs are highly effective in reducing relapse disease biology and overall, are very well tolerated. It also highlights the importance of advocating for reliable access and coverage for CD20Mabs for pwMS, which have been deemed World Health Organisation essential medicines. ^{Reference Laurson-Doube, Helme, Nonino, Piggott, Rijke and Saylor5} The optimal duration and dosing of CD20 monoclonal antibody therapy remain under investigation, ^{Reference Hogenboom, van Kempen, Kalincik, Bar-Or and Killestein6} with adherence and tolerability being key considerations; this study offers real-world insights into both.

Finally, future studies on whether other CD20Mabs (e.g. ofatumumab, a fully human subcutaneous formulation) or other patient populations (ocrelizumab for primary progressive MS) have different rates and reasons for discontinuation would be of interest to clinicians who treat pwMS.