Ocrelizumab dosing, is it overkill?

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This paper is part of the reason why ocrelizumab is a commonly used treatment

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population.Fernandez-Diaz E, Perez-Vicente JA, Villaverde-Gonzalez R, Berenguer-Ruiz L, Candeliere Merlicco A, Martinez-Navarro ML, Gracia Gil J, Romero-Sanchez CM, Alfaro-Saez A, Diaz I, Gimenez-Martinez J, Mendez-Miralles MA, Millan-Pascual J, Jimenez-Pancho J, Mola S, Sempere AP.Ann Clin Transl Neurol. 2020 Dec 25. doi: 10.1002/acn3.51282. 

Objective: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited (yarn). The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting.

Methods: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved.

Results: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19.

Interpretation: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.

However, being commonly used means that there is most data relating he influence of COVID-19 and CD20 depleting antibodies. They are the mosted influenced by (incresed risk of CoviD-19/hospitalisaton) and influenced on (blunted or absent antibody reponse with natural infection) agents. Whilst the manufacturer is doing alot to put this in perspective and may argue that there is limited effect of ocrelizumab with regards to cOVID-19 infection. There are a number of papers that suggest otherwise and we know that SH1 sticks.

With the fear factor at play. as COVID-!9 arrived..the call was “Schtop” which meant doses of ocrelizumab were being delayed from the six monthly dosing schedule. Four years ago, I went out on a limb to suggest that ocrelizumab was being over dosed and that an extended dose interval could be relatively safe based on a plausible biology and less dosing should investigated. Little did I know that COVID-19 was going to cause this experiment to be done. I think we have done an audit but there are few novel ideas and if you “snooze you Loose” so others data.

Influence of delaying ocrelizumab dosing in multiple sclerosis due to COVID-19 pandemics on clinical and laboratory effectiveness.Barun B, Gabelić T, Adamec I, Babić A, Lalić H, Batinić D, Krbot Skorić M, Habek M.Mult Scler Relat Disord. 2020;48:102704

Objective: To evaluate clinical and laboratory effects of delaying ocrelizumab infusions during the COVID-19 pandemics in people with multiple sclerosis (pwMS).

Methods: We have retrospectively searched our electronic database and identified 33 pwMS who had a delay in treatment due to COVID-19 pandemics. The following data were extracted: age, sex, multiple sclerosis (MS) phenotype: relapsing-remitting (RRMS) or primary progressive multiple sclerosis (PPMS), disease duration, Expanded Disability Status scale (EDSS), previous disease modifying therapy (DMT), number of ocrelizumab cycles prior to the lockdown, dates of first ocrelizumab infusion, last ocrelizumab infusion prior to the lockdown and delayed ocrelizumab infusion after the lockdown. Flow cytometry results, relapses and EDSS progression prior to the delayed ocrelizumab infusion after the lockdown were extracted.

Results: The mean time between two ocrelizumab infusion during the lockdown was 7.72±0.64 (range 6.07 to 8.92) months. The mean time between last ocrelizumab infusion and the lymphocyte sampling prior to post COVID infusion was 6.59±0.95 (range 5.18 to 8.49) months. In this period, none of the studied patients had a relapse. In a multivariable linear regression analysis, time from last ocrelizumab infusion to lymphocyte sampling prior to the next infusion was the only significant predictor for CD19+ B cells count, when corrected for the number of previous ocrelizumab cycles and MS phenotype (RRMS or PPMS) (B=7.981, 95% C.I. 3.277-12.686, p=0.002).

Conclusions: We have not shown clinical consequences of delaying ocrelizumab due to COVID-19 pandemics. However, the delay in dosing of ocrelizumab was an independent predictor of repopulation of B cells.

By 6 monthly treating there are no B cell recovered but a small amount of CD19 repopulation occurs ther after. I have argued that most of these cells will e irrelevant to MS as they are not the disease related cells. To answer the first question> i Think the answer is yes…overkill, but we need studies to show that it is safe. We need the ADIOS trial

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