Tolerability and Safety of Switching from Rituximab to Ocrelizumab: Evaluating Factors Associated with Infusion Related Reactions

Abstract

Background Ocrelizumab and rituximab are frequently used treatments for multiple sclerosis (MS). Data on switching from rituximab to ocrelizumab is limited. Objectives To assess the frequency, severity, and factors of infusion related reactions (IRRs) in patients with MS who switch from rituximab to ocrelizumab, compared to those who stay on rituximab. Methods Prospective study on MS patients aged 18–65, on rituximab for at least 2 cycles, who either switched to ocrelizumab (switch group) or stayed on rituximab (comparator group) (n = 100 each). Participants were followed for IRRs, safety, and tolerability over 12 months. Results The proportion of IRRs in patients who continue on rituximab (14%) were similar to those who switched to ocrelizumab on Day 1 (14%; p = 1.000) and Week 24 (12%; p = 0.647) but higher than at Day 15 (4%; 0.005). The risk of IRRs for the switch group was associated with the presence of B cells (CD19 and/or CD20 counts ≥1%) increasing by 5.01 (1.49, 16.82) times on Day 1 (p = 0.007). Antidrug antibodies to ocrelizumab were not associated with IRRs. No other safety concerns were identified in switching to ocrelizumab. Conclusion IRRs are similar between both groups, which suggests that it is safe to switch from rituximab to ocrelizumab.

Relevance of Pathogenetic Mechanisms to Clinical Effectiveness of B-Cell-Depleting Monoclonal Antibodies in Multiple Sclerosis

“…The production of anti-rituximab antibodies is observed in 36% of treated patients affected by RR-MS and 26% of those affected by progressive MS [ 99 ]. On the other hand, the proportion of those developing anti-mAb antibodies is low in ocrelizumab-treated patients: 0.4 and 1.9%, respectively [ 100 ]. Anti-Ab antibody production is negligible in patients treated with ofatumumab, which is constituted by human sequences only.…”

Ublituximab: A Novel Anti-CD20 Therapy for Multiple Sclerosis

“…Mechanistically, reactions occur due to rapid lysis of B-cells with resultant cytokine release, as suggested by more frequent infusion reactions when B-cells are present at the time of infusion, and from pre-medications themselves, such as sedation from antihistamines. 24 In the ULTIMATE studies, 47.7% of ublituximab-treated patients reported an infusion reaction, with 43.3% of these occurring in the first infusion; most had no further infusion reactions compared with 12.2% of placebo infusions. 6 Most reactions were mild, with 2.8% being grade 3 or higher and with two grade 4 reactions, one of which was anaphylaxis on the second dose.…”

Infusion-Related Reactions with Anti-CD20 Monoclonal Antibody Treatments in Multiple Sclerosis: Traditional Review

“…Generally, grade 1 or 2 reactions are observed, but in rare cases, reactions can lead to life-threatening situations. [8][9][10] Therefore, it is important to monitor patients during the infusion. In studies evaluated rapid infusion, which aimed to reduce the use of hospital resources, it was observed that rapid infusion regimen did not change the safety profile of drugs in patients who could tolerate the first dose without infusion-related reactions.…”