ECTRIMS2021 Ocrelizumab and Rituximab in the real world are the the same?


Casanova et al. P871 – Rituximab – Ocrelizumab comparison in real-world practice

Introduction: Several anti-CD20 drugs have demonstrated their efficacy in multiple sclerosis (MS) but there is an ongoing debate about the differences of these medications.
Objective and aims: To compare the effectiveness and safety profile of rituximab (RTX) and ocrelizumab (OCZ) in real-world practice.
Methods: retrospective longitudinal study. 1 year follow-up.
Inclusion criteria: patients diagnosed with MS according to McDonald 2017 attending at the demyelinating unit of Hospital Torrejon or Hospital QuironSalud Madrid treated with RTX or OCZ and who gave their consent to participate in the study. Escalation to 2-line treatment with anti-CD20 and type of anti-CD20 was decided by the treating physicians regarding their regular clinical practice.
Demographic, clinical and MRI data: sex, clinical course of MS, age of MS onset, type of anti-CD20 drug, age at anti-CD20 onset, annualized relapse rate (ARR), prior disease modifying treatments, EDSS, new/enlarging T2 lesions (T2) and contrast-enhancement T1 lesions (CEL) were obtained.
Descriptive data: 40 patients. 11 OCZ, 29 RTX. 29 female (OCZ: 6). 20 relapsing – remitting MS (RRMS) (OCZ: 5), 16 se. No differences in clinical and demographic composition between the 2 groups
Effectiveness. No differences in AAR (p=0.62) and EDSS progression (p=0.61) between the 2 groups. No new T2 or CEL in any group. Safety: No side effects reported with OCZ. 6 adverse reactions with RTX: 1 transient tremor in upper extremities < 24h, 1 urinary tract infection, 1 bacterial respiratory infection and 3 withdrawals: 1 cervical cancer, 2 serum-sickness like reaction (SSLR). 1 of these 2 patients changed to OCZ without further side effects. 
Conclusions: RTX and OCZ appear to be equally effective for the treatment of MS. RTX was associated with more side effects, especially severe infusion reactions (SSLR), which occurred more frequently than previously reported.

Quintanilla-Bordá et al,. P817 – Anti-CD20 monoclonal antibodies in primary progressive multiple sclerosis: a real-life comparative study of rituximab vs. ocrelizumab

Introduction: Ocrelizumab is authorized to treat patients with primary progressive MS (pwPPMS). However, in the European Union it is restricted to pwPPMS with active disease.  Rituximab, another antiCD-20 treatment, has demonstrated efficacy in a selected group of pwPPMS, and has also been widely used, especially before ocrelizumab approval as compassionate use. However, head-to-head studies comparing the efficacy of both drugs are lacking.
Methods: This is a multicentric prospective study of pwPPMS treated with ocrelizumab or rituximab according to local health authorities’ guidelines, with a minimum follow-up of one year. All patients signed an informed consent, and the study was approved by the ethics committee at UPH-La Fe. PPMS was diagnosed according to McDonald criteria. All patients had baseline brain MRI, were visited every three months, and serum light neurofilament (sNFL) were measured by SIMOa technology at the end of the follow-up. Primary end point was time to confirmed disease worsening (CDW), defined as an EDSS increase of 1.0 (or 0.5 if EDSS > 5.5) sustained at 3 months after treatment initiation.
Results: 95 out of 111 pwPPMS accomplished our inclusion criteria. 49 (51.6%) received rituximab and 46 (48.4%) ocrelizumab. 45 (47.4%) were female, mean age at treatment initiation was 49.9 years (SD 9.4), mean time to treatment was 6.8 years (SD 6.0), mean EDSS 5.0 (SD 1.4). No differences in sex or age were present. Rituximab-treated patients had higher basal EDSS (5.8 vs 4.8) and time to treatment initiation (8.4 vs 5,2 years). After a mean follow-up of 29.2 months (SD 20.5), 26 patients experienced CDW (21.4%); 15 (30.6%) in the rituximab group; and 11 (23.9%) in the ocrelizumab group, with no differences between them. sNFL were measured in 46 patients (22 in the rituximab group and 24 in the ocrelizumab group), and no differences between groups were found (18.6 pgr/mL in the rituximab group, and 12.4 pgr/mL in the ocrelizumab group).
Conclusion: Our results show similar findings to trials using antiCD20 therapies in pwPPMS but in real-life conditions. Rituximab has similar effectiveness to ocrelizumab and therefore could be used in settings where ocrelizumab is restricted.

These say that rituximab and ocrelizumab are similar when used in real life. It is not surprising as they both do the same thing and deplete CD20 B cells (see below)…but the studies are just too small to say they are different. You could argue this is because they are so similar.

However we know that ocrelizumab is a much more efficicent B cell depleter and this is probably why there are few infusion reactions, coupled with the fact that there is alot more mouse in rituximab making it more immunogenic and this would be a cause of serum sickness. The infusion reactions come from popping B cells and with ocrelizumab there are fewer their to pop as they dont repopulate as quickly before the next injection cycle. Also there was a hint that the progression was slower in ocrelizumab treated individuals and this may become different if a decent size study was down. Progression is usually not measured at 3 months but confirmed 6 and 12 month progression is used and likewise it is better to rebaseline to 6 months before measuring progression.

Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis.Cellerino M, Boffa G, Lapucci C, Tazza F, Sbragia E, Mancuso E, Bruschi N, Minguzzi S, Ivaldi F, Poirè I, Laroni A, Mancardi G, Capello E, Uccelli A, Novi G, Inglese M.Neurotherapeutics. 2021 Sep 22:1-10. doi: 10.1007/s13311-021-01104-8. Online ahead of print

The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs).

One hundred and fifty-three subjects were included (93 RRMS; 84 females). Median follow-up was 1.9 (1.3-2.7). At 2-year follow-up (FU), disability worsening-free survival were 90.5%, 64.7%, and 68.8% for RRMS, primary-progressive MS (PPMS), and secondary-progressive MS (SPMS) patients, respectively. At 2-year FU, 67.1%, 72.7%, and 81.3% of patients with RRMS, PPMS, and SPMS were free of MRI activity, with NEDA-3 percentages of 62.1%, 54.6%, and 55.1%, respectively. Lower baseline EDSS was independently associated with a reduced risk of disability worsening (HR(95%CI) = 1.45(1.05-2.00), p = 0.024) and previous treatment exposure was independently associated with increased probability of radiological activity (HR = 2.53(1.05-6.10), p = 0.039). At 6-month FU, CD8 + cell decrease was less pronounced in patients with inflammatory activity (p = 0.022). Six patients (3.9%) discontinued ocrelizumab due to severe AEs. Our findings suggest that ocrelizumab is an effective treatment in real-world patients with RRMS and PMS, with a manageable safety profile. Better outcomes were observed in treatment-naïve patients and in patients with a low baseline disability level. Depletion of CD8 + cells could underlie early therapeutic effects of ocrelizumab.

It is often argued that CD20+ T cells mediate the effect of ocrelizumab, ignoring the massive depletion by B cells. However in this study the greater the depletion of total CD8 cells the less inflammatory activity was present. This doesnt seem to fit with the idea of CD20+ T cells, Maybe these are the main culprets…I just doubt it.

COI Multiple

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.

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  • Not surprised. What is surprising to me however, is the slightly worse side effect profile of rituximab (apart from the higher incidence of infusions related reactions, which i guess make sense since ocrelizumab is more humanized).

  • I have only one comment. Drug companies show with rituximab story that they not really cares about their patients only the money. Instead of working for approval of rituximab 10-12 years ago they startet a “lookalike” drug and it took 10-12 years before they had an approved drug CD20. In the meantime MS patients waited for an effective approved drug. Many MS fates could have been different if the drugcompanies had ethics and morals on top of the zillions of dollars they make anyhow, Some doctors started using rituximab and they were threatened by lawsuits and even the Swedish state/government were threatened by lawsuits. In Sweden they have used rituximab for 15-20 years, especialle in the north of Sweden. In norway who started using rituximab for 3 years ago, Biotec used to give som research money every year to Haukeland Hospital, but withdrew the money because they used rituximab on 200 patients. Again- no morals in the drug company “department”.

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