Ocrelizumab is more active than rituximab..Infectionwise

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Caldito NG, Shirani A, Salter A, Stuve O. Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database. Mult Scler. 2020;1352458520949986. doi:10.1177/1352458520949986

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.

Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug-AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1.

Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug-AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively).

Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.

Why is it speculative? The have not read our paper.,,,, We know that rituximab does not deplete B cells anywhere near as effectively as ocrelezumab. The B cells are probably depleted for about 6 months more, it has a higher a better killing potentual due to enhanced effector activity


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The AEs included in the immune system category included hypersensitivity and anaphylactic shock which could indicate a more severe allergic reaction to the rituximab infusion. This is because there is more mouse bits in rituximab than ocrelizumab.

There were more infections reported with ocrelizumab, but we have to remember this a registry for adverse events and the question is what is the demoninator because there clearly a lot more people with MS using ocrelizumab than ritximab and as only ocrelizumab is FDA approved and the records came from the states

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  • Ear pruritus? Was it really reported?! I will let you know if I will start scratching my ear…

    Those data look a bit strange to me, it is true that ocrelizumab has higher effector activity and so on but we see higher number of infections but also nearly one third of neoplasms for ocrelizumab. It is true that the number and the percentage is small and maybe rituximab is used in older patients (age is risk factor for cancer).
    Another thing, I think that most of the data for ocrelizumab come from clinical trials while rituximab data come only from FDA registry and maybe many events linked to rtx are not reported.
    It is hard to think that every patient or physician reports every cold or flu in real life setting while I expect them to be accurately reported in clinical studies. Shortly I think there is probably under reporting of RTX AEs and data may also not be age matched, so I would not take the conclusions for final.

    Can you link your paper, please? Maybe I have missed it and I am curious to see depletion data. Thank you.

    • Too much has been invested in the T cell-centric model of autoimmunity for it to be ditched now,. Your not going to get those who built their careers on the back of it to admit it was all a huge waste of time. For things to change you have to wait till they die off.

  • Have to pop this question in somewhere before I get distracted by a squirrel and it falls out of my head. What if rituxan benefit isn’t a B or T cell thing, but a complement thing. There’s some noise that complement system dysfunction may be cause of neurodegenerative diseases and reports of rituxan depleting CNS complement in CNS lymphomas and claims that i.t. rituxan doesn’t adequately clean out B cells in PPMS even though PPMS has high levels of complement activation in CNS. What if knocking out complement for a time stops the “real ms/crazy complement cascade,” allowing brain tissues to heal until complement dysfunction gets out of hand again and resumes the breaking down of tissues w inflammation? Perhaps this is why the benefit of my four weekly it and iv rituxan doses lasts so long? One dose depletes complement for up to 4 days (from what I’ve quickly dug up). But w weekly doses, complement is depleted until doses stop. PPMS study i.t. doses were 6 weeks apart and only two doses were administered. NFL levels remained high because complement not depleted long enough to stop self-feeding complement cascade? I know this is oversimplified but I still have to ask. Thoughts?

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