Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic

Abstract

In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203–24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients.

Repeated iv anti‐CD20 treatment in multiple sclerosis: Long‐term effects on peripheral immune cell subsets

“…47 In another study, however, an OCR infusion delay of at least 4 weeks was associated with an increased risk of MRI activity. 48 Nonetheless, although B-cell repletion kinetics varied widely, memory B cells seemed to repopulate slower than total B-cell counts, reaching the lower level of normal (LLN) only after 16 months, while the number of total B cells reached the LLN already after 12 months. 47 The optimal overall treatment duration of B cell-depleting therapies has not been established.…”

“…However, it is advisable to exercise caution as there might be radiological activity during extended dosing intervals, especially in patients with a shorter time on OCR or a shorter disease duration in general. 48 Recently, it was suggested that anti-CD20 therapies could also act as immune reconstitution therapies in the fashion of alemtuzumab or cladribine. 50 A strong correlation was present between OCR treatment, disease activity reduction, and decreased serum neurofilament light chain levels (sNfL).…”

Ocrelizumab extended‐interval dosing in multiple sclerosis during SARS‐CoV‐2 pandemic: a real‐world experience

“…Finally, retrospective data derived from a German multicentre cohort (318 RRMS patients, 116 undergoing ocrelizumab delay) also suggest dose extension as a possible risk mitigation strategy [6]. Only one recent multicentre Italian study (278 RRMS patients, 104 experiencing dose delay) reported an increased risk of neuroradiological reactivation; overall MRI activity rates, however, were very low [7].…”

“…As for these previous reports [3‐7], the main limitations of our study consist in its retrospective nature, sample size (a quite large single‐centre cohort was enrolled, but our observations are obviously underpowered compared to the average numerosity of randomized trials), absence of standardized MRI and laboratory protocols, and the relatively short follow‐up with ocrelizumab delay being sporadic and not systematic.…”

“…RRMS and PRMS patients were merged into a relapsing MS (RMS) cohort. According to available literature [5][6][7], enrolled subjects were classified upon the occurrence (extended-interval dose, EID) or not (standard interval dose, SID) of a delay of at least 4 weeks (dosing interval ≥7 months) in at least one ocrelizumab administration. MS history, B-cell counts and MRI examinations performed per clinical practice have been reviewed.…”