Anti-CD20 Therapies Shown to Be Effective After Switch From Natalizumab

This article was originally published by NeurologyLive.

In a small-scale study presented at MSMilan 2023, the 9th Joint ECTRIMS-ACTRIMS Meeting, held October 11-13, in Milan, Italy, findings showed that the use of anti-CD20 therapies after natalizumab (Tysabri; Biogen) were effective in treating multiple sclerosis (MS), with most disease progression being independent of relapse activity (PIRA).¹

Senior investigator Inês Correia, department of neurology, Coimbra Hospital and University Center, Coimbra, Portugal, and colleagues studied a sample of 59 patients, most of which had relapsing-remitting MS, with a mean age of 39.33 years at natalizumab switch. Natalizumab, which has been approved since 2004, is considered a highly effective agent; however, it carries a significant risk of developing progressive multifocal leukoencephalopathy (PML), a life-threatening disease caused by the reactivation of JC virus.

Multiple sclerosis illustration | Image credit: Juan Gärtner - stock.adobe.com

In the retrospective study, patients with MS switched from natalizumab to an anti-CD20 therapy of either rituximab, ocrelizumab (Ocrevus; Genetech), or ofatumumab (Kesimpta; Novartis). In the subgroup of rituximab (n = 23), 21.7% of patients switched because of inefficacy whereas in the ocrelizumab group (n = 29), most patients switched for safety concerns (96.6%). Most of the total cohort were female (69.5%), with demographic, clinical, and safety data evaluated over time.

For the rituximab group, after a mean treatment duration of 48.57 months, annualized relapses rates were reduced from 0.65 to 0.08 (P = .007); however, most patients (43.5%) continued showed disease activity. At the end of follow-up, nearly three-fourths (73.9%) of patients showed no disability progression despite significant increases in overall Expanded Disability Status Scale (EDSS) scores (3.65 vs 5.15; P = .022). Investigators determined that half of these patients had PIRA-related progression. The therapy was stopped in 39.1% of the patients, most of which was related to inefficacy (66.7%).

In the ocrelizumab subgroup, reports of disease activity were much lower, as 13.8% of treated patients demonstrated this over an 18-month period. Throughout that time, there were no significant changes in ARR (0.03 vs 0.07) or EDSS (2.4 vs 2.52), with disability worsening reported in 10.3% of patients, all of which were PIRA-related.

Among those who switched to ofatumumab (n = 7), investigators observed no relapses reported and no significant chances in mean EDSS (2.0 vs 2.14) over a treatment duration of 6.86 months. The switch to this therapy was soley related to safety concerns, with no relapses in the previous year. PIRA was reported in 1 patient, and all individuals continued on with ofatumumab.

There has been some literature about exit strategies for patients potentially looking to discontinue natalizumab. In early 2021, a retrospective observational study compared the effectiveness, tolerability, and safety of switching disease-modifying therapy (DMT) treatment in patients with relapsing MS with a high JC virus antibody index and at least 24 infusions from natalizumab to ocrelizumab (n = 64), rituximab (n = 36), or cladribine (n = 20). Published in Neurotherapeutics, the study’s primary outcome was ARR with additional outcome MRI activity after 12 months and 12 weeks confirmed disability progression (CDP).²

At the conclusion of that study, the inverse probability treatment weighting (IPTW) propensity-score-adjusted models revealed that patients on ocrelizumab had a lower risk for ARR than those who switched to cladribine (ExpB, 0.485; 95% CI, 0.264-0.893; P = .020). This result was also confirmed for 12-month MRI activity (ExpB, 0.248; 95% CI, 0.065-0.948; P = .042). Regarding CDP, no differences were found, at the end of follow-up, between the 3-switching group. Overall, the DMTs used had a good safety profile with no cases of PML.

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References

1. Cuhna C, Matos S, Carvalho IV, et al. Effectiveness of anti-CD20 therapies after natalizumab. Presented at: MSMilan2023, October 11-13, Milan, Italy. Abstract 723

2. Zanghi A, Gallo A, Avolio C, et al. Exit strategies in natalizumab-treated RRMS at high risk of progressive multifocal leukoencephalopathy: a multicentre comparison study. Neurotherapeutics. 2021;18(2):1166-1174. doi:10.1007/s13311-021-01037-2