Efficacy of Ocrelizumab Versus Rituximab in Patients With Relapsing-remitting Multiple Sclerosis

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Hegazy, Nirmeen Kishk, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4752481/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Apr, 2025 Read the published version in Acta Neurologica Belgica → Version 1 posted You are reading this latest preprint version Abstract Background Ocrelizumab (OCR) and rituximab (RTX) are monoclonal antibodies binding to CD20, inducing B-cell depletion. The randomized controlled trials that compare their effectiveness in people with Multiple sclerosis (pwMS) are still ongoing. This study aims at comparing the efficacy of ocrelizumab (OCR) and rituximab (RTX) in treating pwMS. Methods We conducted a retrospective cohort study in patients with relapsing remitting multiple sclerosis (RRMS) treated with either OCR or RTX. Patients were recruited from the Kasr Al-Ainy MS research unit (KAMSU) at Cairo University, Egypt. Data were collected at least one year of the first anti-CD20 infusion. The primary outcome was the time to 3-month confirmed disability worsening (3 month-CDW). Secondary outcomes were time to first relapse (TTFR), 3-month confirmed disability improvement (CDI), annualized relapse rate (ARR), and magnetic resonance imaging (MRI) activity. Results 126 patients were included in the analysis: 64 (50.8%) received OCR, and 62 (49.2%) received RTX. There was no significant difference between patients receiving OCR and RTX in CDW (9.37% vs. 11.29%), CDI (21.87% vs. 30.64%), mean ARR (0.21 vs. 0.29). There was no significant difference in TTFR, cumulative hazard of relapses or time to 3 months-CDW between both groups. Conclusion No difference in efficacy between ocrelizumab and rituximab in treating RRMS Multiple sclerosis Ocrelizumab Rituximab Efficacy Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). It affects about 2.8 million people worldwide, and around 60,000 people in Egypt [ 1 ]. Ocrelizumab (OCR) and rituximab (RTX) are monoclonal antibodies that bind to CD20, a surface marker expressed on B cells, and induce their depletion. OCR was approved by the Food and Drug Administration (FDA) in 2017 for the treatment of RRMS and PPMS based on the results of three phase III trials: Opera I and II for RRMS and ORATORIO for PPMS.[ 2 , 3 ] RTX had been tested in RRMS patients in a phase II placebo-controlled trial, demonstrating its clinical and radiological efficacies [ 4 ]. RTX was also tested in PPMS patients in the OLYMPUS trial, RTX did not significantly slow down the progression of the disease. However, in subgroup analyses, it was shown to slow down the progression of the disease in young (< 51 years) PPMS patients and in patients with contrast enhancing lesions [ 5 ]. Despite the promising results, clinical development of RTX was interrupted, probably due to the emergence of newer B-cell-depleting therapies (ocrelizumab). However, rituximab is still used as an off-label alternative to ocrelizumab with very good safety and efficacy [ 5 – 8 ]. Although both RTX and OCR were tested in similar clinical contexts in pwMS, the randomized controlled trials that compare their effectiveness in MS patients are still ongoing [ 9 ]. Moreover, observational studies comparing these drugs are scarce [ 10 ] [ 11 ]. To address this gap, the aim of this study was to compare the effectiveness of RTX and OCR in RRMS patients. Methods This was a retrospective cohort observational analytic study conducted on 126 patients with relapsing remitting multiple sclerosis (RRMS), diagnosed according to the revised McDonald criteria of 2010 and 2017. Patients were treated with either ocrelizumab (OCR) or rituximab (RTX). Patients attended the Kasr Al-Ainy MS unit (KAMSU) clinic at Cairo University hospital, Egypt, from August 18, 2022, to April 1, 2023. Included patients were 18–60 years old of both sexes and received either ocrelizumab or rituximab for at least 12 months. Baseline characteristics and outcomes at least one year after the first anti-CD20 infusion and until the most recent follow-up visit were recorded. Relapse history for up to 24 months prior to starting RTX or OCR and until the most recent follow-up visit or discontinuing or switching from the anti-CD20 was recorded. Relapses were confirmed by the patient’s treating neurologist and documented in the medical record. The annualized relapse rate (ARR) was defined as the number of confirmed relapses per year. The time to first relapse is defined as the time 3 months after initiating anti-CD20 to the first reported relapse in the follow-up period. (Lublin et al., 2022) Baseline Expanded Disability Status Scale (EDSS) was documented 3 months prior to anti-CD20 treatment. Confirmed Disability Worsening (CDW) was defined as an increase in EDSS; either ≥ 1.5 points for patients with a baseline EDSS of zero, ≥ 1.0 points for patients with a baseline EDSS of 1–5, or 0.5 points for patients with a baseline EDSS of ≥ 5.5, EDSS was confirmed 3 months after the onset of worsening (3-months CDW).Confirmed disability improvement was defined as a decrease in EDSS of either ≥ 1.0 points if baseline EDSS 1–5, or ≥ 0.5 for patients with a baseline EDSS of ≥ 5.5, confirmed at least 3 months after initial improvement [ 12 ]. Patient was considered stable if EDSS score increased or decreased by 0.5 points compared to the baseline if the baseline score was < 5.5, or no change in score if baseline EDSS score was ≥ 5.5 [ 13 ]. Time to 3-month confirmed disability worsening is defined as the time from treatment initiation to the first observed increase in EDSS above the threshold (not the time of confirmation). To confirm a progression or improvement, EDSS scores recorded more than 30 days from the onset of a preceding relapse were used (Lublin et al., 2022). A baseline brain MRI was performed before starting the anti-CD20 and another re-baseline brain MRI 3 months after starting the anti-CD20 treatment. Follow-up brain MRI was performed 12 months after starting the anti-CD20, and then every 12 months unless otherwise indicated. MRI activity was determined by presence of new/enlarging lesions, or contrast enhancing lesions. Safety and tolerability data were collected throughout the duration of the study, including infusion-related reactions (IRRs) and adverse events (AEs). IRRs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 of the National Cancer Institute. Rituximab dosing regimen consisted of two 500 mg infusions two weeks apart, then a single 1000 mg infusion every 6 months. Ocrelizumab regimen consisted of two 300 mg infusions two weeks apart, then a single 600 mg infusion every six months. Pre-medications were given routinely and included 16 mg of dexamethasone (or the equivalent of 100 mg of methylprednisolone) 30 minutes prior to infusion, as well as an antihistamine 30 to 60 minutes prior to infusion, to reduce the incidence and severity of IRRs and acetaminophen 1000 mg was also given. Statistical analysis : The results were analyzed using Statistical Package for the Social Sciences (SPSS) version 26 (IBM Corp., 2019). Numbers and percentages were used to represent qualitative data. The mean and standard deviation (SD) or median (range) of numerical variables were used. The Kolmogorov–Smirnov single-sample test was used to determine the data’s normality. Comparison between two groups for numerical variables was done using either a student t-test or a Mann-Whitney U test (non-parametric t-test) as appropriate. The chi-square or Fisher's exact test was used for qualitative variables. Kaplan–Meier estimator was used for survival analysis, and a comparison between curves was performed with the log-rank test. Independent prognostic factors were estimated by the Cox proportional hazards in regression model. A probability (p-value) equal to or less than 0.05 is considered significant. To calculate the relapse rate for each subject (subject-based), we divided the number of relapses they had by the number of days they were in the study and then multiplied the ratio by 365.25. Based on these individual relapse rates, the mean and median for each treatment group were to be presented. Results Cohort of 234 patients were recruited; however, 109 patients were omitted from both groups due to incomplete data, short treatment duration, SPMS or PPMS patients. Therefore, 126 patients were included in the final analysis: 64 (50.8%) on ocrelizumab and 62 (49.2%) on rituximab. (Fig. 1) Baseline characteristics : There was no significant difference between the OCR and RTX groups as regards age at time of anti-CD20 initiation (mean ± SD 30.56 ± 8.33 years vs. 32.99 ± 8.95 years respectively; p = 0.117), disease duration (mean ± SD 7.2 ± 3.7 years vs.8.3 ± 4.1 years respectively; p = 0.139 ) , baseline EDSS (3.3 ± 1.2 vs.3.6 ± 1.1 respectively, p = 0.201), and annualized relapse rate prior to anti-CD20 initiation (1.4 ± 0.7 vs.1.33 ± 0.8 respectively; p = 0.413), number of relapses within 2 years before starting anti-CD20 (2.3 ± .9, vs.2.2 ± .9 respectively; p = 0.730), and activity in baseline MRI brain (35.9%, vs 40.3%, respectively; p = 0.754). also, most patients in both OCR and RTX group were previously treated with other disease modifying drugs (DMTs) with no significant difference, (70.3% vs, 67.7%). Baseline characteristic is summarized in Table 1 . Clinical outcomes : Most patients in both groups were stable in the EDSS (58.3% vs. 61.2%). At the end of the follow-up period, 6 (9.37%) patients of the ocrelizumab group and 7 (11.29%) patients of the rituximab group had a confirmed 3-month CDW, with no significant difference between the two groups (P. Value 0.449). CDI was confirmed in 14 patients (21.8%) of the ocrelizumab group and in 19 patients (30.64%) of the rituximab group with no significant difference between the two groups (P. Value 0.449). ( Table 2 , Fig. 2 ) Time to 3-months confirmed disability worsening (CDW) : Survival analysis revealed no differences in time to 3 months CDW (primary outcome) and mean time to 3-month CDW in ocrelizumab group was 42.6 months (95% CI 39.2–46.1) and 34.8 months (95% CI 32.1–37.4) for the rituximab group with no significant difference between the two groups (p = 0.970) and the cumulative hazard of disability accumulation (hazard ratio,1.021, 95% CI, 0.339–3.078, p = 0.970) (Fig. 3) Time to first relapse (TTFR) : Ocrelizumab showed a non-significantly longer time to first relapse than rituximab (mean, 36.1 vs. 24.5 months; p = 0.051 ). additionally, no significant difference between the groups on the cumulative hazard of relapses (hazard ratio, 1.9; 95% CI, 0.9–3.5, p = 0.054 ). (Fig. 4) MRI related outcomes :No significant difference was found between ocrelizumab and rituximab groups as regards presence/absence of new/enlarging lesions or enhancing lesions in follow-up MRI brain. Infusion related reaction, infections, and malignancy : Rituximab patients experienced a significant higher incidence of IRRS than ocrelizumab patients (59.7% vs 42.2%, respectively, p = 0.050). In ocrelizumab group, 11 (17%) of the patients developed infections. Respiratory infections were the most common (4), followed by herpes zoster (2). Two serious infections were observed: both were severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) that required hospitalization. In rituximab group, 10 (16%) of patients developed infections. severe SARS-COV-2 (4) and urinary tract infections (3) were the most common. Malignancy was reported in a 30-year-old female who developed thyroid swelling after being on ocrelizumab for 3 years. In the rituximab group, two patients developed atypical lymphadenopathy. Table 1 Baseline characteristic Ocrelizumab (OCR) Rituximab (RTX) P value Gender number (%) Male 20 (31.3%) 11 (17.7%) 0.078 Female 44 (68.8%) 51 (82.3%) DMTs number (%) Previously treated with DMTs 45 (70.3%) 42 (67.7%) 0.755 Naïve 19 (29.7%) 20 (32.3%) Types of prior DMTs number (%) Naïve 19 (29.7%) 20 (32.3%) 0.527 Interferon 10 (15.6%) 15 (24.2%) fingolimod 29 (45.3%) 25 (40.3%) Dimethyl fumarate 3(4.7%) 0 (0.0%) Teriflunomide 1 (1.6%) 1 (1.6%) Natalizumab 1(1.6%) 0 (0.0%) Azathioprine 1(1.6%) 1 (1.6%) Baseline MRI activity MRI activity No 29 (45.3%) 24 (38.7%) 0.754 MRI activity Yes 23 (35.9%) 25 (40.3%) No baseline MRI 12 (18.8%) 13 (21.0%) Age at starting anti-CD20 (years) Mean ± SD 30.55 ± 8.33 32.99 ± 8.95 0.117 Median (range) 30.56 (17.8–51.3) 33 (17.3–50) Number relapse within 2 years before treatment Mean ± SD 2.3 ± .9 2.2 ± .9 0.730 Median (range) 2 (1–5) 2 (1–5) ARR within 2 years before anti-CD20 Mean ± SD 1.4 ± 0.78 1.33 ± 0.88 0.413 Median (range) 1(0.5–4.3) 1(0.5-6) Median (range) 6 (2–15) 7 (2–20) Baseline Expanded Disability Status Scale (EDSS) Mean ± SD 3.3 ± 1.2 3.6 ± 1.1 0.201 Median (range) 3.5 (1-5.5) 3.5 (1–6) Table 2 Clinical Outcome Ocrelizumab Rituximab P value Duration of anti-CD20 treatment Mean ± SD 18 ± 7.37 20.85 ± 8.2 0.048 Median(range) 16 (10–47) 18 (12–43) ARR after treatment Mean ± SD 0.21 ± 0.4 0.29 ± 0.4 0.253 Median(range) 0(0-1.4) 0(0-1.8) Last observed EDSS Mean ± SD 3 ± 1.37 3.28 ± 1.23 0.241 Median(range) 2.5 (1–6) 3.25 (1-5.5) FU MRI brain No MRI activity N (%) 33(51%) 28 (45.2%) 0.213 MRI activity N (%) 5 (7.8%) 7 (11.3%) MRI lesion regression N (%) 1 (1.6%) 6 (9.7%) No follow up brain MRI N (%) 25 (39.1%) 21 (33.9%) N = Number Discussion Ocrelizumab (OCR) and rituximab (RTX) are monoclonal antibodies that bind to CD20 inducing their depletion. This study conducted to compare the effectiveness of these two drugs in treating RRMS in a real-world setting. Both ocrelizumab and rituximab were found to significantly reduce the annualized relapse rate (ARR) when compared to pre-treatment. Furthermore, our study showed no significant difference in the time to 3-month CDW or the percentage of patients who experienced 3-month CDW or 3-month CDI between the two groups. These results are in agreement with Vollmer B. (2023), who compared the efficacy and safety of ocrelizumab and rituximab over 24 months. When comparing both groups, no significant difference was found in the follow-up MRI activity consistent with the results Zanghi et al. in (2021) and Vollmer B. in (2023).[ 14 , 15 ] After ocrelizumab treatment, ARR significantly decreased from 1.4 to 0.21, consistent with findings from Opera 1 and 2 trials and observational studies.[ 16 – 18 ] Rituximab also showed a significant reduction in ARR from 1.33 to 0.29, consistent with the HERMES trial ,Yamout et al. in (2018), and Zecca et al. in (2020)[ 7 , 8 ]. 9.37% of ocrelizumab group experienced CDW, similar to rates reported in OPERA I and II, Pontieri et al. (2022), and Zanghì et al. (2021).[ 15 , 17 ] However, it was higher compared to Fernandez-Diaz et al. (2021)[ 17 ], possibly due to differences in baseline EDSS and follow-up duration. CDI was observed in 21.8% of ocrelizumab-treated patients, aligning with results from the OPERA I and II trials, Fernandez-Diaz et al. (2021), Sempere et al. (2021), and Pontieri et al. (2022). [ 17 – 20 ] Among rituximab-treated patients, 11.29% experienced CDW, similar to Scotti et al. (2018) and Zecca et al. (2020), but lower than Yamout et al. (2018), potentially due to the longer follow-up in the latter study. [ 7 , 8 , 20 ] These findings indicate the effectiveness of both ocrelizumab and rituximab in reducing disability worsening and improving outcomes in patients with active disease. Our study employed survival analysis to estimate the time to first relapse in RRMS, suggesting a trend toward a significant difference between the two drugs. Specifically, the ocrelizumab group had a longer time to first relapse (p = 0.051). The incidence of infusion-related reactions (IRRs) in patients treated with ocrelizumab in our study cohort was 42.2%. These findings were higher than the rates reported in phase 3 trials OPERA I and II (34% and 31%, respectively) [ 20 ] as well as the ORATARIO trial (39.9%)[ 4 ]. This difference may be attributed to the potential underreporting of mild IRRs in other populations. These results are very important for MS practice in developing countries with suffering economies like Egypt in light of the increasing costs of MS treatments, especially monoclonal Abs like Ocrelizumab. However, the study was limited by sample size, the lack of radiological correlations due to incomplete MRI data, number of drop out in follow up MRI studies was large which affected the reliability of MRI results and the fact that most of patients had their MRI scans done at different centers on different machines with variable quality, which renders objective comparisons and objective results impossible. For future research, we would recommend a bigger cohort with longer follow-up periods, better follow up MRI data, inclusion of progressive MS patients and inclusion of radiological correlation through complete and uniform MRI data.This study demonstrates that there is no significant difference in the effectiveness of ocrelizumab and rituximab in controlling disability accumulation, relapse activity, and MRI activity among patients with relapsing remitting multiple sclerosis. Abbreviations ARR: Annualized relapsing rate AEs: Adverse events CDI: Confirmed disability improvement. CDW: Confirmed disability worsening. CNS: Central nervous system CTCAE: Common Terminology Criteria for Adverse Events EDSS: Expanded disability status scale. FDA: Food and Drug Administration IRR: Infusion related reaction KAMSU: Kasr Al-Ainy MS research unit PMS: progressive multiple sclerosis PPMS: Primary progressive multiple sclerosis PwMS: People with multiple sclerosis MRI: Magnetic resonance imaging MS: Multiple Sclerosis OCR: Ocrelizumab P.Value: Probability value RMS: Relapsing multiple sclerosis. RRMS: Relapsing remitting multiple sclerosis RTX: Rituximab SARS-COV2: severe acute respiratory syndrome coronavirus 2 SD: Standard deviations SPMS: Secondary progressive multiple sclerosis SPSS: Statistical Program for Social Science TTFR: Time to first relapse Declarations Ethics approval and consent to participate. Ethical approval was obtained from the “Research ethical committee (REC) Cairo university Faculty of medicine, Code (MS-165-2022). Consent for publication : Not applicable. Availability of data and materials : The datasets generated and/or analyzed during the current study are not publicly available due to the current Cairo University regulations and Egyptian legislation, but they are available by a reasonable request from the corresponding author. Competing interests: None of the authors has any conflict of interest. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author s' contributions: N.M.: data analysis , manuscript writing and reviewing workup N.S.: analyzed research idea, data acquisition, data analysis and interpretation M.I.H: analyzed research idea, data interpretation. N.K. data analysis and interpretation H.S.: data acquisition and interpretation and manuscript reviewing. S.A.A. performed statistical analysis A.M.A. performed data acquisition, data analysis N.M. data analysis and interpretation. Acknowledgement: The authors acknowledge subjects for their participation and cooperation in this study. Authors' information : a Faculty of Medicine, Cairo University b Applied Medical Sciences, Albaha University. c Faculty of Medicine, Aden University References Walton, C., et al., Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler, 2020. 26 (14): p. 1816-1821. Hauser, S.L., et al., Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. New England Journal of Medicine, 2017. 376 (3): p. 221-234. Montalban, X., et al., Ocrelizumab versus placebo in primary progressive multiple sclerosis. New England Journal of Medicine, 2017. 376 (3): p. 209-220. Hauser, S.L., et al., B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. New England Journal of Medicine, 2008. 358 (7): p. 676-688. 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SAGE PUBLICATIONS LTD 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND. Roos, I., et al., Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. JAMA Neurol, 2023. 80 (8): p. 789-797. Lublin, F.D., et al., How patients with multiple sclerosis acquire disability. Brain, 2022. 145 (9): p. 3147-3161. Cree, B.A., J.R. Oksenberg, and S.L. Hauser, Multiple sclerosis: two decades of progress. The Lancet Neurology, 2022. 21 (3): p. 211-214. Vollmer B, N.K., Sillau S, Corboy JR, Alvarez E. Comparison of ocrelizumab and rituximab over 2 years of treatment for multiple sclerosis. Presented at: 2023 ACTRIMS Forum; February 23-25; San Diego, California. Abstract P159. Zanghì, A., et al., Exit strategies in natalizumab-treated RRMS at high risk of progressive multifocal leukoencephalopathy: a multicentre comparison study. Neurotherapeutics, 2021. 18 : p. 1166-1174. Fernandez‐Diaz, E., et al., Real‐world experience of ocrelizumab in multiple sclerosis in a Spanish population. Annals of Clinical and Translational Neurology, 2021. 8 (2): p. 385-394. Pontieri, L., et al., Ocrelizumab treatment in multiple sclerosis: a Danish population‐based cohort study. European Journal of Neurology, 2022. 29 (2): p. 496-504. Sempere, A.P., et al., Ocrelizumab in multiple sclerosis: a real-world study from Spain. Frontiers in Neurology, 2021. 11 : p. 592304. Hauser, S.L., et al., Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med, 2017. 376 (3): p. 221-234. Scotti, B., et al., Effectiveness and safety of Rituximab in multiple sclerosis: an observational study from Southern Switzerland. PLoS One, 2018. 13 (5): p. e0197415. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4752481","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":335550128,"identity":"17988577-9c02-4993-a2a3-ac4d0193535f","order_by":0,"name":"Nesma Mounir","email":"data:image/png;base64,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","orcid":"","institution":"Cairo university","correspondingAuthor":true,"prefix":"","firstName":"Nesma","middleName":"","lastName":"Mounir","suffix":""},{"id":335550129,"identity":"69cd50ba-b1db-414f-a472-e842dc34f104","order_by":1,"name":"Nevin Shalaby","email":"","orcid":"","institution":"Cairo university","correspondingAuthor":false,"prefix":"","firstName":"Nevin","middleName":"","lastName":"Shalaby","suffix":""},{"id":335550130,"identity":"715c4a2c-c51a-4011-8285-0c7116b180ef","order_by":2,"name":"Mohamed I. Hegazy","email":"","orcid":"","institution":"Cairo university","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"I.","lastName":"Hegazy","suffix":""},{"id":335550131,"identity":"de7683ac-2b4c-4626-bc72-989fbabc3259","order_by":3,"name":"Nirmeen Kishk","email":"","orcid":"","institution":"Cairo university","correspondingAuthor":false,"prefix":"","firstName":"Nirmeen","middleName":"","lastName":"Kishk","suffix":""},{"id":335550132,"identity":"1f30640e-c291-4994-8a15-b03859dccc42","order_by":4,"name":"Hatem Shehata","email":"","orcid":"","institution":"Cairo university","correspondingAuthor":false,"prefix":"","firstName":"Hatem","middleName":"","lastName":"Shehata","suffix":""},{"id":335550133,"identity":"82e0ec19-3b3f-4959-8eec-50e232a8fbbc","order_by":5,"name":"Shaimaa abdalaleem Abdalgeleel","email":"","orcid":"","institution":"Albaha University","correspondingAuthor":false,"prefix":"","firstName":"Shaimaa","middleName":"abdalaleem","lastName":"Abdalgeleel","suffix":""},{"id":335550134,"identity":"5418ef4c-7cd2-4e61-87d4-f3e5888eab16","order_by":6,"name":"Ahmed Mohammed Abdulrahman","email":"","orcid":"","institution":"Faculty of Medicine, Aden University","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Mohammed","lastName":"Abdulrahman","suffix":""},{"id":335550136,"identity":"5f62d435-e687-4311-8192-a9eb187ad120","order_by":7,"name":"Nahla Merghany","email":"","orcid":"","institution":"Cairo university","correspondingAuthor":false,"prefix":"","firstName":"Nahla","middleName":"","lastName":"Merghany","suffix":""}],"badges":[],"createdAt":"2024-07-16 22:26:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4752481/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4752481/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s13760-025-02766-3","type":"published","date":"2025-04-12T16:05:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62659583,"identity":"d6e7d0ad-42dd-4612-ad0a-c868735bf532","added_by":"auto","created_at":"2024-08-17 02:27:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":490198,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInitial study cohort\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(\u003cstrong\u003eN\u003c/strong\u003e: Number, \u003cstrong\u003eOCR\u003c/strong\u003e: Ocrelizumab, \u003cstrong\u003eRTX\u003c/strong\u003e: Rituximab)\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4752481/v1/5e04b7a9397b7a623562f4c4.png"},{"id":62659584,"identity":"493d8c9d-ee50-43ab-b6b0-dce528f03741","added_by":"auto","created_at":"2024-08-17 02:27:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50649,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConfirmed disability at the end of follow-up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4752481/v1/ef446989bf7f36219020ee1c.png"},{"id":62659585,"identity":"db679443-fc9e-4aa0-840d-30a69a46bc84","added_by":"auto","created_at":"2024-08-17 02:27:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":221934,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival analysis curve of time to 3-month CDW. \u003c/strong\u003eThe ocrelizumab group and the rituximab group are shown with a blue and green continuous line, respectively. No difference in time to 3-months CDW (p= 0.970 log rank test).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4752481/v1/45980e1509613f79b83d7e0d.png"},{"id":62659582,"identity":"f0c50f18-4a88-4258-8b8f-a22f920f37d9","added_by":"auto","created_at":"2024-08-17 02:27:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":40392,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival analysis curve of time to first relapse. \u003c/strong\u003eThe ocrelizumab group and the rituximab group are shown with a blue and green line, respectively. No significant differences in time to first relapse were encountered (p = 0.051, log rank test)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4752481/v1/1942e11bc113b81c4b73660f.png"},{"id":80558256,"identity":"3cf26c77-2fe6-461c-8857-d8fc708ee841","added_by":"auto","created_at":"2025-04-14 16:13:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2042630,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4752481/v1/d7016c2a-f02b-4ad4-a371-01fea8fed11f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEfficacy of Ocrelizumab Versus Rituximab in Patients With Relapsing-remitting Multiple Sclerosis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). It affects about 2.8\u0026nbsp;million people worldwide, and around 60,000 people in Egypt [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Ocrelizumab (OCR) and rituximab (RTX) are monoclonal antibodies that bind to CD20, a surface marker expressed on B cells, and induce their depletion. OCR was approved by the Food and Drug Administration (FDA) in 2017 for the treatment of RRMS and PPMS based on the results of three phase III trials: Opera I and II for RRMS and ORATORIO for PPMS.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] RTX had been tested in RRMS patients in a phase II placebo-controlled trial, demonstrating its clinical and radiological efficacies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. RTX was also tested in PPMS patients in the OLYMPUS trial, RTX did not significantly slow down the progression of the disease. However, in subgroup analyses, it was shown to slow down the progression of the disease in young (\u0026lt;\u0026thinsp;51 years) PPMS patients and in patients with contrast enhancing lesions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite the promising results, clinical development of RTX was interrupted, probably due to the emergence of newer B-cell-depleting therapies (ocrelizumab). However, rituximab is still used as an off-label alternative to ocrelizumab with very good safety and efficacy [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Although both RTX and OCR were tested in similar clinical contexts in pwMS, the randomized controlled trials that compare their effectiveness in MS patients are still ongoing [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Moreover, observational studies comparing these drugs are scarce [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. To address this gap, the aim of this study was to compare the effectiveness of RTX and OCR in RRMS patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a retrospective cohort observational analytic study conducted on 126 patients with relapsing remitting multiple sclerosis (RRMS), diagnosed according to the revised McDonald criteria of 2010 and 2017. Patients were treated with either ocrelizumab (OCR) or rituximab (RTX). Patients attended the Kasr Al-Ainy MS unit (KAMSU) clinic at Cairo University hospital, Egypt, from August 18, 2022, to April 1, 2023. Included patients were 18\u0026ndash;60 years old of both sexes and received either ocrelizumab or rituximab for at least 12 months. Baseline characteristics and outcomes at least one year after the first anti-CD20 infusion and until the most recent follow-up visit were recorded. Relapse history for up to 24 months prior to starting RTX or OCR and until the most recent follow-up visit or discontinuing or switching from the anti-CD20 was recorded. Relapses were confirmed by the patient\u0026rsquo;s treating neurologist and documented in the medical record. The annualized relapse rate (ARR) was defined as the number of confirmed relapses per year. The time to first relapse is defined as the time 3 months after initiating anti-CD20 to the first reported relapse in the follow-up period. (Lublin et al., 2022) Baseline Expanded Disability Status Scale (EDSS) was documented 3 months prior to anti-CD20 treatment. Confirmed Disability Worsening (CDW) was defined as an increase in EDSS; either \u0026ge;\u0026thinsp;1.5 points for patients with a baseline EDSS of zero, \u0026ge;\u0026thinsp;1.0 points for patients with a baseline EDSS of 1\u0026ndash;5, or 0.5 points for patients with a baseline EDSS of \u0026ge;\u0026thinsp;5.5, EDSS was confirmed 3 months after the onset of worsening (3-months CDW).Confirmed disability improvement was defined as a decrease in EDSS of either \u0026ge;\u0026thinsp;1.0 points if baseline EDSS 1\u0026ndash;5, or \u0026ge;\u0026thinsp;0.5 for patients with a baseline EDSS of \u0026ge;\u0026thinsp;5.5, confirmed at least 3 months after initial improvement [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Patient was considered stable if EDSS score increased or decreased by 0.5 points compared to the baseline if the baseline score was \u0026lt;\u0026thinsp;5.5, or no change in score if baseline EDSS score was \u0026ge;\u0026thinsp;5.5 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Time to 3-month confirmed disability worsening is defined as the time from treatment initiation to the first observed increase in EDSS above the threshold (not the time of confirmation). To confirm a progression or improvement, EDSS scores recorded more than 30 days from the onset of a preceding relapse were used (Lublin et al., 2022).\u003c/p\u003e \u003cp\u003eA baseline brain MRI was performed before starting the anti-CD20 and another re-baseline brain MRI 3 months after starting the anti-CD20 treatment. Follow-up brain MRI was performed 12 months after starting the anti-CD20, and then every 12 months unless otherwise indicated. MRI activity was determined by presence of new/enlarging lesions, or contrast enhancing lesions.\u003c/p\u003e \u003cp\u003eSafety and tolerability data were collected throughout the duration of the study, including infusion-related reactions (IRRs) and adverse events (AEs). IRRs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 of the National Cancer Institute. Rituximab dosing regimen consisted of two 500 mg infusions two weeks apart, then a single 1000 mg infusion every 6 months. Ocrelizumab regimen consisted of two 300 mg infusions two weeks apart, then a single 600 mg infusion every six months. Pre-medications were given routinely and included 16 mg of dexamethasone (or the equivalent of 100 mg of methylprednisolone) 30 minutes prior to infusion, as well as an antihistamine 30 to 60 minutes prior to infusion, to reduce the incidence and severity of IRRs and acetaminophen 1000 mg was also given. \u003cb\u003eStatistical analysis\u003c/b\u003e: The results were analyzed using Statistical Package for the Social Sciences (SPSS) version 26 (IBM Corp., 2019). Numbers and percentages were used to represent qualitative data. The mean and standard deviation (SD) or median (range) of numerical variables were used. The Kolmogorov\u0026ndash;Smirnov single-sample test was used to determine the data\u0026rsquo;s normality. Comparison between two groups for numerical variables was done using either a student t-test or a Mann-Whitney U test (non-parametric t-test) as appropriate. The chi-square or Fisher's exact test was used for qualitative variables. Kaplan\u0026ndash;Meier estimator was used for survival analysis, and a comparison between curves was performed with the log-rank test. Independent prognostic factors were estimated by the Cox proportional hazards in regression model. A probability (p-value) equal to or less than 0.05 is considered significant. To calculate the relapse rate for each subject (subject-based), we divided the number of relapses they had by the number of days they were in the study and then multiplied the ratio by 365.25. Based on these individual relapse rates, the mean and median for each treatment group were to be presented.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCohort of 234 patients were recruited; however, 109 patients were omitted from both groups due to incomplete data, short treatment duration, SPMS or PPMS patients. Therefore, 126 patients were included in the final analysis: 64 (50.8%) on ocrelizumab and 62 (49.2%) on rituximab. \u003cb\u003e(Fig.\u0026nbsp;1) Baseline characteristics\u003c/b\u003e: There was no significant difference between the OCR and RTX groups as regards age at time of anti-CD20 initiation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD 30.56\u0026thinsp;\u0026plusmn;\u0026thinsp;8.33 years vs. 32.99\u0026thinsp;\u0026plusmn;\u0026thinsp;8.95 years respectively; p\u0026thinsp;=\u0026thinsp;0.117), disease duration (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD 7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 years vs.8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 years respectively; p\u0026thinsp;=\u0026thinsp;0.139\u003cb\u003e)\u003c/b\u003e, baseline EDSS (3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 vs.3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 respectively, p\u0026thinsp;=\u0026thinsp;0.201), and annualized relapse rate prior to anti-CD20 initiation (1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 vs.1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 respectively; p\u0026thinsp;=\u0026thinsp;0.413), number of relapses within 2 years before starting anti-CD20 (2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;.9, vs.2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;.9 respectively; p\u0026thinsp;=\u0026thinsp;0.730), and activity in baseline MRI brain (35.9%, vs 40.3%, respectively; p\u0026thinsp;=\u0026thinsp;0.754). also, most patients in both OCR and RTX group were previously treated with other disease modifying drugs (DMTs) with no significant difference, (70.3% vs, 67.7%). Baseline characteristic is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cb\u003eClinical outcomes\u003c/b\u003e: Most patients in both groups were stable in the EDSS (58.3% vs. 61.2%). At the end of the follow-up period, 6 (9.37%) patients of the ocrelizumab group and 7 (11.29%) patients of the rituximab group had a confirmed 3-month CDW, with no significant difference between the two groups (P. Value 0.449). CDI was confirmed in 14 patients (21.8%) of the ocrelizumab group and in 19 patients (30.64%) of the rituximab group with no significant difference between the two groups (P. Value 0.449). \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e) Time to 3-months confirmed disability worsening (CDW)\u003c/b\u003e : Survival analysis revealed no differences in time to 3 months CDW (primary outcome) and mean time to 3-month CDW in ocrelizumab group was 42.6 months (95% CI 39.2\u0026ndash;46.1) and 34.8 months (95% CI 32.1\u0026ndash;37.4) for the rituximab group with no significant difference between the two groups (p\u0026thinsp;=\u0026thinsp;0.970) and the cumulative hazard of disability accumulation (hazard ratio,1.021, 95% CI, 0.339\u0026ndash;3.078, p\u0026thinsp;=\u0026thinsp;0.970) (Fig.\u0026nbsp;3) \u003cb\u003eTime to first relapse (TTFR)\u003c/b\u003e: Ocrelizumab showed a non-significantly longer time to first relapse than rituximab (mean, 36.1 vs. 24.5 months; \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.051\u003c/b\u003e). additionally, no significant difference between the groups on the cumulative hazard of relapses (hazard ratio, 1.9; 95% CI, 0.9\u0026ndash;3.5, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.054\u003c/b\u003e). (Fig.\u0026nbsp;4) \u003cb\u003eMRI related outcomes\u003c/b\u003e :No significant difference was found between ocrelizumab and rituximab groups as regards presence/absence of new/enlarging lesions or enhancing lesions in follow-up MRI brain. \u003cb\u003eInfusion related reaction, infections, and malignancy\u003c/b\u003e: Rituximab patients experienced a significant higher incidence of IRRS than ocrelizumab patients (59.7% vs 42.2%, respectively, p\u0026thinsp;=\u0026thinsp;0.050). In ocrelizumab group, 11 (17%) of the patients developed infections. Respiratory infections were the most common (4), followed by herpes zoster (2). Two serious infections were observed: both were severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) that required hospitalization. In rituximab group, 10 (16%) of patients developed infections. severe SARS-COV-2 (4) and urinary tract infections (3) were the most common. Malignancy was reported in a 30-year-old female who developed thyroid swelling after being on ocrelizumab for 3 years. In the rituximab group, two patients developed atypical lymphadenopathy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristic\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOcrelizumab (OCR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRituximab\u003c/p\u003e \u003cp\u003e(RTX)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGender number (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (31.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (17.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (68.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51 (82.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eDMTs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003enumber (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePreviously treated with DMTs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (70.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42 (67.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNa\u0026iuml;ve\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (29.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e\u003cb\u003eTypes of prior DMTs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003enumber (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNa\u0026iuml;ve\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (29.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterferon\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (24.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003efingolimod\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eDimethyl fumarate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTeriflunomide\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNatalizumab\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAzathioprine\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eBaseline MRI activity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMRI activity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.754\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMRI activity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (35.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo baseline MRI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (21.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eAge at starting anti-CD20 (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.55\u0026thinsp;\u0026plusmn;\u0026thinsp;8.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.99\u0026thinsp;\u0026plusmn;\u0026thinsp;8.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMedian (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.56 (17.8\u0026ndash;51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (17.3\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eNumber relapse within 2 years before treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.730\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMedian (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eARR within 2 years before anti-CD20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMedian (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(0.5\u0026ndash;4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1(0.5-6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMedian (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (2\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eBaseline Expanded Disability Status Scale (EDSS)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5 (1-5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.5 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical Outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOcrelizumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRituximab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eDuration of anti-CD20 treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;7.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.85\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (10\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (12\u0026ndash;43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eARR after treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0-1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0-1.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLast observed EDSS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.25 (1-5.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFU MRI brain\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo MRI activity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRI activity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (11.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRI lesion regression\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo follow up brain MRI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (39.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (33.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eN\u0026thinsp;=\u0026thinsp;Number\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOcrelizumab (OCR) and rituximab (RTX) are monoclonal antibodies that bind to CD20 inducing their depletion. This study conducted to compare the effectiveness of these two drugs in treating RRMS in a real-world setting. Both ocrelizumab and rituximab were found to significantly reduce the annualized relapse rate (ARR) when compared to pre-treatment. Furthermore, our study showed no significant difference in the time to 3-month CDW or the percentage of patients who experienced 3-month CDW or 3-month CDI between the two groups. These results are in agreement with Vollmer B. (2023), who compared the efficacy and safety of ocrelizumab and rituximab over 24 months. When comparing both groups, no significant difference was found in the follow-up MRI activity consistent with the results Zanghi et al. in (2021) and Vollmer B. in (2023).[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] After ocrelizumab treatment, ARR significantly decreased from 1.4 to 0.21, consistent with findings from Opera 1 and 2 trials and observational studies.[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Rituximab also showed a significant reduction in ARR from 1.33 to 0.29, consistent with the HERMES trial ,Yamout et al. in (2018), and Zecca et al. in (2020)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. 9.37% of ocrelizumab group experienced CDW, similar to rates reported in OPERA I and II, Pontieri et al. (2022), and Zangh\u0026igrave; et al. (2021).[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] However, it was higher compared to Fernandez-Diaz et al. (2021)[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], possibly due to differences in baseline EDSS and follow-up duration. CDI was observed in 21.8% of ocrelizumab-treated patients, aligning with results from the OPERA I and II trials, Fernandez-Diaz et al. (2021), Sempere et al. (2021), and Pontieri et al. (2022). [\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Among rituximab-treated patients, 11.29% experienced CDW, similar to Scotti et al. (2018) and Zecca et al. (2020), but lower than Yamout et al. (2018), potentially due to the longer follow-up in the latter study. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] These findings indicate the effectiveness of both ocrelizumab and rituximab in reducing disability worsening and improving outcomes in patients with active disease. Our study employed survival analysis to estimate the time to first relapse in RRMS, suggesting a trend toward a significant difference between the two drugs. Specifically, the ocrelizumab group had a longer time to first relapse (p\u0026thinsp;=\u0026thinsp;0.051). The incidence of infusion-related reactions (IRRs) in patients treated with ocrelizumab in our study cohort was 42.2%. These findings were higher than the rates reported in phase 3 trials OPERA I and II (34% and 31%, respectively) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] as well as the ORATARIO trial (39.9%)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This difference may be attributed to the potential underreporting of mild IRRs in other populations. These results are very important for MS practice in developing countries with suffering economies like Egypt in light of the increasing costs of MS treatments, especially monoclonal Abs like Ocrelizumab. However, the study was limited by sample size, the lack of radiological correlations due to incomplete MRI data, number of drop out in follow up MRI studies was large which affected the reliability of MRI results and the fact that most of patients had their MRI scans done at different centers on different machines with variable quality, which renders objective comparisons and objective results impossible. For future research, we would recommend a bigger cohort with longer follow-up periods, better follow up MRI data, inclusion of progressive MS patients and inclusion of radiological correlation through complete and uniform MRI data.This study demonstrates that there is no significant difference in the effectiveness of ocrelizumab and rituximab in controlling disability accumulation, relapse activity, and MRI activity among patients with relapsing remitting multiple sclerosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eARR:\u0026nbsp;Annualized relapsing rate\u003c/p\u003e\n\u003cp\u003eAEs:\u0026nbsp;Adverse events\u003c/p\u003e\n\u003cp\u003eCDI:\u0026nbsp;Confirmed disability improvement.\u003c/p\u003e\n\u003cp\u003eCDW:\u0026nbsp;Confirmed disability worsening.\u003c/p\u003e\n\u003cp\u003eCNS:\u0026nbsp;Central nervous system\u003c/p\u003e\n\u003cp\u003eCTCAE:\u0026nbsp;Common Terminology Criteria for Adverse Events\u003c/p\u003e\n\u003cp\u003eEDSS: Expanded disability status scale.\u003c/p\u003e\n\u003cp\u003eFDA:\u0026nbsp;Food and Drug Administration\u003c/p\u003e\n\u003cp\u003eIRR:\u0026nbsp;Infusion related reaction\u003c/p\u003e\n\u003cp\u003eKAMSU: Kasr Al-Ainy MS research unit\u003c/p\u003e\n\u003cp\u003ePMS: progressive multiple sclerosis\u003c/p\u003e\n\u003cp\u003ePPMS: Primary progressive multiple sclerosis\u003c/p\u003e\n\u003cp\u003ePwMS: People with multiple sclerosis\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eMS: Multiple Sclerosis\u003c/p\u003e\n\u003cp\u003eOCR: Ocrelizumab\u003c/p\u003e\n\u003cp\u003eP.Value: Probability value\u003c/p\u003e\n\u003cp\u003eRMS: Relapsing multiple sclerosis.\u003c/p\u003e\n\u003cp\u003eRRMS: Relapsing remitting multiple sclerosis\u003c/p\u003e\n\u003cp\u003eRTX: Rituximab\u003c/p\u003e\n\u003cp\u003eSARS-COV2:\u0026nbsp;severe acute respiratory syndrome coronavirus 2\u003c/p\u003e\n\u003cp\u003eSD: Standard deviations\u003c/p\u003e\n\u003cp\u003eSPMS: Secondary progressive multiple sclerosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSPSS: Statistical Program for Social Science\u003c/p\u003e\n\u003cp\u003eTTFR: Time to first relapse\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Ethical approval was obtained from the \u0026ldquo;Research ethical committee (REC) Cairo university Faculty of medicine, Code (MS-165-2022).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e: The datasets generated and/or analyzed during the current study are not publicly available due to the current Cairo University regulations and Egyptian legislation, but they are available by a reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e None of the authors has any conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026nbsp;s\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN.M.:\u003c/strong\u003e data analysis , manuscript writing and reviewing workup \u003cstrong\u003eN.S.:\u0026nbsp;\u003c/strong\u003eanalyzed\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eresearch idea, data acquisition, data analysis and interpretation \u003cstrong\u003eM.I.H:\u003c/strong\u003e analyzed\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eresearch idea, data interpretation. \u003cstrong\u003eN.K.\u003c/strong\u003e data analysis and interpretation \u003cstrong\u003eH.S.:\u003c/strong\u003e data acquisition and interpretation and manuscript reviewing. \u003cstrong\u003eS.A.A.\u0026nbsp;\u003c/strong\u003eperformed statistical analysis \u003cstrong\u003eA.M.A.\u003c/strong\u003e performed data acquisition, data analysis \u003cstrong\u003eN.M.\u003c/strong\u003e data analysis and interpretation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003eThe\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eauthors acknowledge subjects for their participation and cooperation in this study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ea\u0026nbsp;Faculty of Medicine, Cairo University\u003c/p\u003e\n\u003cp\u003eb Applied Medical Sciences, Albaha University.\u003c/p\u003e\n\u003cp\u003ec Faculty of Medicine, Aden University\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWalton, C., et al., \u003cem\u003eRising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition.\u003c/em\u003e Mult Scler, 2020. \u003cstrong\u003e26\u003c/strong\u003e(14): p. 1816-1821.\u003c/li\u003e\n\u003cli\u003eHauser, S.L., et al., \u003cem\u003eOcrelizumab versus interferon beta-1a in relapsing multiple sclerosis.\u003c/em\u003e New England Journal of Medicine, 2017. \u003cstrong\u003e376\u003c/strong\u003e(3): p. 221-234.\u003c/li\u003e\n\u003cli\u003eMontalban, X., et al., \u003cem\u003eOcrelizumab versus placebo in primary progressive multiple sclerosis.\u003c/em\u003e New England Journal of Medicine, 2017. \u003cstrong\u003e376\u003c/strong\u003e(3): p. 209-220.\u003c/li\u003e\n\u003cli\u003eHauser, S.L., et al., \u003cem\u003eB-cell depletion with rituximab in relapsing\u0026ndash;remitting multiple sclerosis.\u003c/em\u003e New England Journal of Medicine, 2008. \u003cstrong\u003e358\u003c/strong\u003e(7): p. 676-688.\u003c/li\u003e\n\u003cli\u003eHawker, K., et al., \u003cem\u003eRituximab in patients with primary progressive multiple sclerosis: results of a randomized double‐blind placebo‐controlled multicenter trial.\u003c/em\u003e Annals of neurology, 2009. \u003cstrong\u003e66\u003c/strong\u003e(4): p. 460-471.\u003c/li\u003e\n\u003cli\u003eSalzer, J., et al., \u003cem\u003eRituximab in multiple sclerosis: a retrospective observational study on safety and efficacy.\u003c/em\u003e Neurology, 2016. \u003cstrong\u003e87\u003c/strong\u003e(20): p. 2074-2081.\u003c/li\u003e\n\u003cli\u003eYamout, B.I., et al., \u003cem\u003eSafety and efficacy of rituximab in multiple sclerosis: a retrospective observational study.\u003c/em\u003e Journal of immunology research, 2018. \u003cstrong\u003e2018\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eZecca, C., et al., \u003cem\u003eTreatment of multiple sclerosis with rituximab: a multicentric Italian\u0026ndash;Swiss experience.\u003c/em\u003e Multiple Sclerosis Journal, 2020. \u003cstrong\u003e26\u003c/strong\u003e(12): p. 1519-1531.\u003c/li\u003e\n\u003cli\u003eTecha-Angkoon, P., et al., \u003cem\u003eCurrent evidence of rituximab in the treatment of multiple sclerosis.\u003c/em\u003e Multiple Sclerosis and Related Disorders, 2023: p. 104729.\u003c/li\u003e\n\u003cli\u003eRoos, I., et al. \u003cem\u003eA non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis\u003c/em\u003e. in \u003cem\u003eMULTIPLE SCLEROSIS JOURNAL\u003c/em\u003e. 2022. SAGE PUBLICATIONS LTD 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND.\u003c/li\u003e\n\u003cli\u003eRoos, I., et al., \u003cem\u003eRituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis.\u003c/em\u003e JAMA Neurol, 2023. \u003cstrong\u003e80\u003c/strong\u003e(8): p. 789-797.\u003c/li\u003e\n\u003cli\u003eLublin, F.D., et al., \u003cem\u003eHow patients with multiple sclerosis acquire disability.\u003c/em\u003e Brain, 2022. \u003cstrong\u003e145\u003c/strong\u003e(9): p. 3147-3161.\u003c/li\u003e\n\u003cli\u003eCree, B.A., J.R. Oksenberg, and S.L. Hauser, \u003cem\u003eMultiple sclerosis: two decades of progress.\u003c/em\u003e The Lancet Neurology, 2022. \u003cstrong\u003e21\u003c/strong\u003e(3): p. 211-214.\u003c/li\u003e\n\u003cli\u003eVollmer B, N.K., Sillau S, Corboy JR, Alvarez E. Comparison of ocrelizumab and rituximab over 2 years of treatment for multiple sclerosis. Presented at: 2023 ACTRIMS Forum; February 23-25; San Diego, California. Abstract P159.\u003c/li\u003e\n\u003cli\u003eZangh\u0026igrave;, A., et al., \u003cem\u003eExit strategies in natalizumab-treated RRMS at high risk of progressive multifocal leukoencephalopathy: a multicentre comparison study.\u003c/em\u003e Neurotherapeutics, 2021. \u003cstrong\u003e18\u003c/strong\u003e: p. 1166-1174.\u003c/li\u003e\n\u003cli\u003eFernandez‐Diaz, E., et al., \u003cem\u003eReal‐world experience of ocrelizumab in multiple sclerosis in a Spanish population.\u003c/em\u003e Annals of Clinical and Translational Neurology, 2021. \u003cstrong\u003e8\u003c/strong\u003e(2): p. 385-394.\u003c/li\u003e\n\u003cli\u003ePontieri, L., et al., \u003cem\u003eOcrelizumab treatment in multiple sclerosis: a Danish population‐based cohort study.\u003c/em\u003e European Journal of Neurology, 2022. \u003cstrong\u003e29\u003c/strong\u003e(2): p. 496-504.\u003c/li\u003e\n\u003cli\u003eSempere, A.P., et al., \u003cem\u003eOcrelizumab in multiple sclerosis: a real-world study from Spain.\u003c/em\u003e Frontiers in Neurology, 2021. \u003cstrong\u003e11\u003c/strong\u003e: p. 592304.\u003c/li\u003e\n\u003cli\u003eHauser, S.L., et al., \u003cem\u003eOcrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.\u003c/em\u003e N Engl J Med, 2017. \u003cstrong\u003e376\u003c/strong\u003e(3): p. 221-234.\u003c/li\u003e\n\u003cli\u003eScotti, B., et al., \u003cem\u003eEffectiveness and safety of Rituximab in multiple sclerosis: an observational study from Southern Switzerland.\u003c/em\u003e PLoS One, 2018. \u003cstrong\u003e13\u003c/strong\u003e(5): p. e0197415.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple sclerosis, Ocrelizumab, Rituximab, Efficacy","lastPublishedDoi":"10.21203/rs.3.rs-4752481/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4752481/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOcrelizumab (OCR) and rituximab (RTX) are monoclonal antibodies binding to CD20, inducing B-cell depletion. The randomized controlled trials that compare their effectiveness in people with Multiple sclerosis (pwMS) are still ongoing. This study aims at comparing the efficacy of ocrelizumab (OCR) and rituximab (RTX) in treating pwMS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study in patients with relapsing remitting multiple sclerosis (RRMS) treated with either OCR or RTX. Patients were recruited from the Kasr Al-Ainy MS research unit (KAMSU) at Cairo University, Egypt. Data were collected at least one year of the first anti-CD20 infusion. The primary outcome was the time to 3-month confirmed disability worsening (3 month-CDW). Secondary outcomes were time to first relapse (TTFR), 3-month confirmed disability improvement (CDI), annualized relapse rate (ARR), and magnetic resonance imaging (MRI) activity.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e126 patients were included in the analysis: 64 (50.8%) received OCR, and 62 (49.2%) received RTX. There was no significant difference between patients receiving OCR and RTX in CDW (9.37% vs. 11.29%), CDI (21.87% vs. 30.64%), mean ARR (0.21 vs. 0.29). There was no significant difference in TTFR, cumulative hazard of relapses or time to 3 months-CDW between both groups.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eNo difference in efficacy between ocrelizumab and rituximab in treating RRMS\u003c/p\u003e","manuscriptTitle":"Efficacy of Ocrelizumab Versus Rituximab in Patients With Relapsing-remitting Multiple Sclerosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-17 02:27:46","doi":"10.21203/rs.3.rs-4752481/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4d74f461-2752-4b05-9a64-08ba4a22b7ef","owner":[],"postedDate":"August 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-14T16:07:56+00:00","versionOfRecord":{"articleIdentity":"rs-4752481","link":"https://doi.org/10.1007/s13760-025-02766-3","journal":{"identity":"acta-neurologica-belgica","isVorOnly":false,"title":"Acta Neurologica Belgica"},"publishedOn":"2025-04-12 16:05:06","publishedOnDateReadable":"April 12th, 2025"},"versionCreatedAt":"2024-08-17 02:27:46","video":"","vorDoi":"10.1007/s13760-025-02766-3","vorDoiUrl":"https://doi.org/10.1007/s13760-025-02766-3","workflowStages":[]},"version":"v1","identity":"rs-4752481","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4752481","identity":"rs-4752481","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}