Rituximab In Multiple Sclerosis Research Articles

Efficacy and safety of rituximab in multiple sclerosis and neuromyelitis optica spectrum disorder

In Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20–46) and 31 months (IQR 23–41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42–1.83] to 0 [IQR 0–0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68–1.78] to 0 [IQR 0–0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions.

Ocrelizumab and ofatumumab, but not rituximab, trigger complement induction in vitro

The clinical and adverse effects of the therapeutic monoclonal antibodies (mAb) ocrelizumab, ofatumumab and rituximab in multiple sclerosis (MS) are presently subject to extensive study. While the two former are approved for MS, the older and less costly rituximab is used off label, and adverse effect profiles are important in their evaluation. The three mAbs all induce B cell depletion, with complement-dependent cytotoxicity (CDC) as one of several mechanisms of action. Complement activation is also postulated to underlie adverse reactions related to infusion/injection. Such administration-related reactions are associated with all three mAbs, but comparisons have so far been indirect, resting on incidence reports from separate clinical trials. The objective of this study was to perform head-to-head comparison of complement activation by ofatumumab, ocrelizumab and rituximab. In vitro experiments were performed in whole blood from healthy donors. The complement-activating potential of the three mAbs was analyzed after 30 min of exposure to 0.3 mg/mL or 0.9 mg/mL of each drug, and compared with those of the well-known TNF inhibitory mAbs adalimumab and infliximab, the latter with recognized potential for infusion reactions. Ofatumumab, ocrelizumab, and infliximab, but not rituximab and adalimumab, triggered statistically significant complement activation measured as increased levels of terminal C5b-9 complement complex (TCC), a sensitive marker of such activation. While results demand careful interpretation, they provide an indication of distinct complement-inducing potential among anti-CD20 mAbs currently used to treat MS.

Disease-modifying therapies in multiple sclerosis: A focused review of rituximab.

Treatment for multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, has changed drastically in the last 30 years. Several different disease-modifying therapies are now available, with off-label use of the B-cell-depleting antibody rituximab becoming an increasingly popular choice, as more and more studies report on its effectiveness. The objective of this study was to summarize the current state of evidence for rituximab as a treatment for relapsing-remitting MS (RRMS). A structured literature search was conducted in PubMed, focusing on peer-reviewed studies of adult populations with RRMS. Ongoing trials with rituximab in MS were identified through Clinicaltrials.gov and additional references were identified through review articles. Despite promising results for rituximab as a treatment of MS, the market-authorization holder switched focus from rituximab and discontinued the industry-sponsored trials programme. However, several observational studies, smaller clinical trials and one large investigator-initiated randomized-controlled trial have continued to report fewer clinical relapses, fewer contrast-enhancing lesions on magnetic resonance imaging and better drug survival with rituximab, compared with MS-approved alternatives. Rituximab should be considered as both a first- and second-line therapy option for most MS patients with active, non-progressive disease. However, as an off-label therapy for MS, regulatory approval remains a barrier for wider adoption in many countries.

Efficacy and safety of rituximab in multiple sclerosis: a systematic review and meta-analysis.

We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people with multiple sclerosis (MS). The four databases including PubMed, Scopus, Embase, and Web of Science were comprehensively searched in April 2022. We defined PICO as follows. Problem or study population (P): patients with MS; intervention (I): Rituximab; comparison (C): none; outcome (O): efficacy and safety. After two-step screening, a total of 27 studies entered into our qualitative and quantitative synthesis. Our analysis showed a significant decrease in EDSS score in all patients with MS after treatment (SMD: -0.44, 95% CI -0.85, -0.03). In addition, the ARR was reduced after using rituximab compared to the pre-treatment period (SMD: -0.65, 95% CI -1.55, 0.24) but it was not significant. The most common side effect after rituximab with a pooled prevalence of 28.63% (95% CI 16.61%, 42.33%). Furthermore, the pooled prevalence of infection was 24% in patients with MS (95% CI 13%, 36%). In the end, the pooled prevalence of malignancies after rituximab treatment was 0.39% (95% CI 0.02%, 1.03%). Our findings illustrated an acceptable safety for this treatment. However, further studies with randomized design, long follow-up, and large sample sizes are needed to confirm the safety and efficacy of rituximab in patients with MS.

Current evidence of rituximab in the treatment of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. The immunopathology of MS involves both T and B lymphocytes. Rituximab is one of the anti-CD20 monoclonal antibody therapies which deplete B-cells. Although some anti-CD20 therapies have been approved by the Food and Drug Administration for treatment of MS, rituximab is used off-label. Several studies have shown that rituximab has a good efficacy and safety in MS, including certain specific patient conditions such as treatment-naïve patients, treatment-switching patients, and the Asian population. However, there are still questions about the optimal dose and duration of rituximab in MS due to the different dosing regimens used in each study. Moreover, many biosimilars have become available at a lower cost with comparable physicochemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Thus, rituximab may be considered as a potential therapeutic option for patients without access to standard treatment. This narrative review summarized the evidence of both original and biosimilars of rituximab in MS treatment including pharmacokinetics, pharmacodynamics, clinical efficacy, safety, and dosing regimen.

B-lymphocyte-guided retreatment contributes to establish good effectiveness and safety profile in MS patients treated with rituximab

BackgroundRituximab is extensively used for multiple sclerosis (MS) treatment. However, the best dosage remains to be established. It has been proposed that retreatment could be guided by B lymphocyte (BL) percentages. ObjectiveTo establish the best BL value for retreatment with rituximab in MS and to confirm the safety and efficacy of this approach. MethodsA prospective study was done with an exploratory cohort and a confirmatory cohort of MS patients treated with rituximab between 2017 and 2021. The first one comprised 10 MS patients with BL assessed every 3 months after rituximab infusion and retreatment done when BL values were ≥0.5%. The confirmatory cohort included 41 MS patients (41.5% women, 87.8% with secondary progressive MS, median age = 46.3 (interquartile range: 41.3–52.1) years, disease duration = 14.1 (9–19.6) years, EDSS score = 5.5 (4.0–6.5)). The confirmatory cohort was treated with rituximab following the pattern established in the exploratory cohort. ResultsIn the exploratory cohort, ≥0.2% BL was established as the best value for retreatment because in most cases, a substantial increase of BL counts was preceded by initial values of 0.2–0.3%. In the confirmatory cohort, rituximab reduced the annualized relapse rate (ARR 0.56 vs. 0.125, p < 0.001), proportion of patients with appearance of new/enlarged T2 lesions (63.4% vs. 12.2%, p < 0.001), gadolinium-enhancing lesions (39% vs. 0%, p < 0.001), and confirmed disability progression (55% vs. 27.5%, p = 0.037). There were 22 patients (53.7%) who achieved NEDA-3. No patients had severe infections, and 10.7% cases had reduced IgG levels. ConclusionRituximab treatment guided by BL showed high effectiveness and a good safety profile for MS patients after one year of treatment.

Duration of B-cell depletion in patients receiving ocrelizumab or rituximab for Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorders (P7-4.006)

Duration of B-cell depletion in patients receiving ocrelizumab or rituximab for Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorders (P7-4.006)

How important are COVID-19 vaccine responses in patients with MS on disease-modifying therapies?

How important are COVID-19 vaccine responses in patients with MS on disease-modifying therapies?

Extended B-cell depletion beyond 6-months in patients receiving ocrelizumab or rituximab for CNS demyelinating disease

ObjectivesTo investigate the duration of B-cell depletion in a cohort of patients receiving ocrelizumab or rituximab for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD). MethodsWe retrospectively searched our database for patients diagnosed with MS or NMOSD, who were receiving ocrelizumab or rituximab and had available CD19 measurements. We collected demographic data, infusion doses, infusion dates, CD19 absolute counts and percentages, and their collection dates. We paired each infusion with the subsequent CD19 measurements recorded before the next infusion, discarding measurements done during a washout period of 30 days after each infusion. We applied three definitions for B-cell depletion, the most stringent of which was an absolute B-cell count ≤20 cells/uL. ResultsFrom 695 patients with demyelinating diseases in our database, over the period of January 1st 2010 to March 1st 2020, we identified 188 patients (178 with MS and 10 with NMOSD), who had received ocrelizumab or rituximab and had available CD19 measurements. 1054 CD19 measurements were captured. B-cell depletion, as defined above, was recorded as far out as 22.8 months after an ocrelizumab infusion, and 22.3 months after a rituximab infusion. Out of 90 B-cell measurements done ≥8 months (>210 days) after ocrelizumab infusion, 45(50%) measurements showed B-cell depletion. Similarly for rituximab, out of 113 measurements, 49(43%) showed B-cell depletion. ConclusionsThis study demonstrates that B-cell depletion after ocrelizumab and rituximab continues beyond the traditional 6-month re-infusion interval in many patients. Our report provides data that can support clinical trials testing increasing the interval of re-infusion with ocrelizumab and rituximab beyond 6-months guided by B-cell measurements.

Rituximab for the Treatment of Multiple Sclerosis: A Retrospective Observational Cohort in Morocco

Background: RITUXIMAB (RTX) is a chimeric anti-CD20 monoclonal antibody that has initially demonstrated efficacy in patients with B-cell lymphoma. Then, over time, it has demonstrated its efficacy in systemic inflammatory diseases and recently in neurological diseases such as multiple sclerosis (MS). Here we describe our experience with rituximab from one MS center from MOROCCO. Objectives: To investigate the safety and efficacy of Rituximab in MS in a Moroccan population. Methods: A retrospective uncontrolled observational single-center study from January 2017 to July 2020, was including all off-label Rituximab-treated patients with MS with at least 6 months of follow-up. Outcome data were collected and evaluated relapse rate, EDSS score, and adverse events (AEs) from the medical charts. Adverse events grade according to the Common Terminology Criteria for Adverse Events. Results: A total of 63 MS patients were treated with RTX, 47 patients were included, while 12 cases had just initiated treatment and 4 cases were lost to follow-up. The mean age of the patients was 39 ± 12 years with a female predominance (F/M: 1.6). All forms of MS were included, 83% of whom had relapsing-remitting MS. The duration of disease progression was 8 ± 5 years. Median EDSS before RTX initiation was 5.5 (0 - 7). 51% of patients were treated with RTX as second-line therapy after failure of other disease-modifying therapies, whereas 34% received it as first-line therapy. The annualized relapse rates decreased from 0.8 to 0.2 after RTX treatment. The Median EDSS remained unchanged at 71%. Radiological stability was noted in 83.7%, while 13.5% had a single new T2 lesion. Infusion-related AEs occurred during 27.6% of infusions and most were mild. Simple infection grades ≤ 2 were noted in 19%. Abortion occurred in only one patient. Conclusion: Our study confirms the usability of rituximab treatment for MS in the MOROCCO healthcare environment.

К ПРОБЛЕМЕ СВЯЗИ ИММУНОТЕРАПИИ У ПАЦИЕНТОВ, СТРАДАЮЩИХ РЕЦИДИВИРУЮЩИМ РАССЕЯННЫМ СКЛЕРОЗОМ, С РИСКОМ ТЯЖЕЛОГО ТЕЧЕНИЯ COVID-19

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS). Anti-CD 20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS has been documented; it is presently prescribed for more than half of all treated MS patients. The rationale for the increasing prescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in addi- tion to the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of se- vere COVID-19 in association with RTX exposure within this group. The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n=approximately 18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demo- graphic parameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg. A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19 (as re- ported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89; p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring 2020, resulting in a ma- jority of patients receiving RTX infusions with extended intervals in order to reduce the risk of severe COVID-19 infection. Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infec- tion. These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients.

THE RISK OF COVID-19 SEVERITY IN PATIENTS WITH MS APPEARS TO BE ASSOCIATED WITH IMMUNOTHERAPY

Immunomodulatory drugs are important to control disease activity in relapsing-remitting multiple sclerosis (MS). Anti-CD 20-therapy is one of such medications. In Sweden, extensive off label prescription of rituximab (RTX) in MS has been documented; it is presently prescribed for more than half of all treated MS patients. The rationale for the increasing prescription of RTX was previous data from phase II and observational studies supporting high efficacy and safety, in addi- tion to the financial aspect. We report national data on usage of disease modifying therapies in MS patients and risk of se- vere COVID-19 in association with RTX exposure within this group. The Swedish National MS Registry (SMSreg) aims to cover all patients with MS in the country, (n=approximately 18,000). After COVID-19 pandemic started in Sweden, a new section was established in it to register clinical and demo- graphic parameters in COVID-19-infected patients. Data presented in the current report were obtained from the SMSreg. A total of 85 out of approximately 6,000 RTX-treated Swedish MS patients had been hospitalized with COVID-19 (as re- ported from the SMSreg, June 16, 2021) and adjusted analyses showed a 2–3 fold increase in a risk (OR = 2.89; p = 0.001) of hospitalization for anti-CD20 treated patients. A change of praxis was introduced in Sweden in spring 2020, resulting in a ma- jority of patients receiving RTX infusions with extended intervals in order to reduce the risk of severe COVID-19 infection. Current Swedish registry data suggest that exposure to RTX in MS may affect the clinical outcome of COVID-19 infec- tion. These observations have rapidly impacted use of immunomodulatory drugs in Swedish MS patients.

Rituximab in Multiple Sclerosis: Are We Ready for Regulatory Approval?

Despite the availability of a lot of effective disease-modifying drugs, multiple sclerosis (MS) (in particular the progressive forms) still represents an important unmet medical need, because of issues in terms of effectiveness, duration of response, safety, and patient compliance. An increasing body of evidence from randomized clinical trials and real-world data suggest that rituximab is a highly effective alternative in both relapsing and progressive MS, with a low discontinuation rate, related to a good benefit/risk profile, and a good compliance. To date, the use of rituximab in patients with multiple sclerosis is not in accordance with the authorized product information (off-label use). However, the use of this medicine is widespread in several countries, and in some cases, it is the most commonly used disease-modifying drug for MS subtypes. This use could be officially recognized by national regulatory authorities, according to specific procedures, to ensure equal access for patients to a safe and effective option.

Modulation of Retinal Atrophy With Rituximab in Multiple Sclerosis.

To investigate the effects of rituximab on retinal atrophy in patients with relapsing-remitting multiple sclerosis (RRMS), we performed serial optical coherence tomography (OCT) scans among a cohort of patients with RRMS on rituximab and compared rates of ganglion cell + inner plexiform layer (GCIPL) atrophy to those observed among age- and sex-matched glatiramer acetate (GA)-and natalizumab-treated patients with RRMS and healthy controls (HCs). In this observational study, patients with RRMS treated with a single disease-modifying therapy and HCs were followed with serial OCT for a median duration of 2.8 years. Participants with uncontrolled hypertension, diabetes mellitus, or glaucoma, and eyes with optic neuritis ≤6 months prior to baseline OCT, or during follow-up, were excluded. Statistical analyses were performed using linear mixed-effects regression. During the overall follow-up period, rates of GCIPL atrophy were -0.28 ± 0.11 µm/y among rituximab-treated patients with RRMS (n = 35). This was similar to GA-treated (n = 49; -0.33 ± 0.05 µm/y; p = 0.69) and natalizumab-treated patients (n = 88; -0.17 ± 0.10 µm/y; p = 0.13) and faster than HCs (n = 78; -0.15 ± 0.03 µm/y; p = 0.006). Rituximab-treated patients exhibited 0.55 ± 0.23 µm/y faster rates of GCIPL atrophy during the first 12 months of treatment, relative to afterwards (n = 25; p = 0.02), during which period GCIPL atrophy rates were -0.14 ± 0.13 µm/y. Retinal atrophy in RRMS is modulated by rituximab. Greater attenuation of retinal atrophy may occur after 12 months of rituximab treatment, following which time GCIPL atrophy rates are similar to those observed among natalizumab-treated patients with RRMS and HCs. Our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, which should be confirmed by larger studies. This study provides Class IV evidence on the difference in rate of change of the GCIPL thickness in patients with RRMS comparing rituximab to other disease-modifying therapies.

Ocrelizumab depletes T-lymphocytes more than rituximab in multiple sclerosis

We aim to directly compare changes in lymphocyte subpopulations between chimeric (rituximab) and humanised (ocrelizumab) anti-CD20 antibodies in multiple sclerosis (MS). In this retrospective analysis of prospectively collected data, we included 88 patients with MS, treated with rituximab (n=50) or ocrelizumab (n=38). We used flow cytometry in the peripheral blood to count total lymphocytes and lymphocytes expressing different phenotypic markers (CD4, CD8, CD19, CD20, CD4/CD8 ratio), before treatment and after 1, 3 and 6 months. On linear mixed effect regression models, after 1, 3 and 6 months, patients treated with rituximab and with ocrelizumab were similar in total lymphocyte count, CD19 lymphocytes, CD20 lymphocytes and CD4/CD8 ratio. However, patients treated with ocrelizumab presented with lower CD4 T lymphocytes and CD8 T lymphocytes after 1, 3 and 6 months (all p<0.05). No between-treatment difference in EDSS progression was found. B-cell levels in the peripheral blood were equally decreased by rituximab and ocrelizumab. On the contrary, CD4 and CD8 T lymphocyte reduction was more pronounced in ocrelizumab, when compared with rituximab, suggesting a broader immunomodulatory effect for the humanised antibody to be confirmed and correlated with clinical efficacy in the long term.

Infusion-Related, Short-term, and Delayed Side Effects of Rituximab in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Background: Rituximab is a monoclonal antibody against CD20 antigen present on mature B lymphocytes. It is commonly used in some hematologic, rheumatologic as well as neurologic disorders, including multiple sclerosis (MS) and neuromyelitis optica (NMO). Although there are some data about the safety of rituximab in patients with MS and NMO, there are few experiences regarding its safety in the Iranian population with MS, and known complications are often related to the studies conducted on the patients in other countries or with other autoimmune diseases and malignancies that are different from the population of patients with MS in terms of the underlying disease status and the concomitant medications or previous medications used. Objectives: The aim of this study was to investigate the infusion related, short-term and delayed side effects of rituximab on patients with MS and NMO in the population of the south of Iran. Methods: This was a longitudinal study on patients with MS and neuromyelitis optica who were referred to the health centers affiliated to Shiraz University of Medical Sciences from September 2018 to February 2019 and received Rituximab. They were observed for side effects from the first infusion of the drug to at least 6 months later. A checklist prepared by the researcher was used to collect the data. Independent t-test and chi-square test were used for data analysis. The significance level was considered 0.05 in this study. Results: In this study, 37% of the patients had at least one side effect during the first infusion. The most common side effect was chills (shivering). Short-term side effects occurred in 15.5% of the patients. The most common type was skin manifestations. These side effects led to hospitalization in two patients. Delayed side effect was developed in 20.7% of the patients. The most common delayed side effect was skin manifestations. Conclusions: Overall, there was no unexpected side effect in patients under the study and the side effects developed were comparable to previous studies as well as those conducted on patients other than patients with MS and neuromyelitis optica. Side effects were often mild, with only two cases leading to hospitalization, both of which were self-limiting as well, and there were no serious life-threatening side effects, except for one case with bradycardia.

Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab

Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS.

A comparative study of tolerability and effects on immunoglobulin levels and CD19 cell counts with ocrelizumab vs low dose of rituximab in multiple sclerosis.

BackgroundRituximab (RTX) and ocrelizumab (OCR) are two anti-CD20 biologics used in MS; however, comparisons on safety and efficacy are rare.ObjectiveTo compare treatment outcomes over the first year with RTX and OCR.MethodsRetrospective cohort study comprising MS patients initiating RTX at the Karolinska University Hospital (Sweden; n = 311) and OCR at Rocky Mountain MS Clinic (Utah, USA; n = 161), respectively.ResultsLevels of immunoglobulin G measured in blood dropped 0.16 g/L (95% confidence interval 0.01 to 0.31) with each OCR infusion, but remained stable with RTX. In contrast, levels of immunoglobulin M decreased to a similar extent with both drugs. Ten and 15% of patients discontinued treatment with RTX and OCR, respectively (n.s), however, adverse events leading to treatment discontinuation were more common with OCR (6.8% vs 2.6%; p = 0.026). Only 3.1 and 1.6% discontinued OCR and RTX, respectively, due to lack of effect (n.s). The degree of B cell depletion was superior with OCR.ConclusionOverall, differences between the two treatments were small. Although the study design precludes robust conclusions regarding the risk-benefit with the studied therapies, our findings indicate that the tolerability and safety with RTX is not inferior to OCR.

Comparative effectiveness of rituximab in multiple sclerosis.

B cell-depleting agents are emerging as important disease-modifying drugs for multiple sclerosis, but their effectiveness in relation to established treatments remains uncertain. To cast light on this issue, several studies have provided head-to-head comparisons of the anti-CD20 antibody rituximab with natalizumab, fingolimod and dimethyl fumarate in patients with multiple sclerosis.

De-escalating rituximab dose results in stability of clinical, radiological, and serum neurofilament levels in multiple sclerosis

Background: Phase II and observational studies support the use of rituximab in multiple sclerosis. Standard protocols are lacking, but studies suggest comparable efficacy between low- and high-dose regimens. Objective: To evaluate effectiveness and safety of de-escalating rituximab dose from 1000 to 500 mg/6 months in multiple sclerosis. Methods: Patients were switched from rituximab 1000 to 500 mg/6 months and prospectively followed for 12 months. Relapses, disability, occurrence of brain/spinal magnetic resonance imaging (MRI) lesions, serum neurofilament light chain (NfL), CD19+ B cell, and IgG concentrations were analyzed. Results: Fifty-nine patients were included (37 relapsing-remitting, 22 secondary progressive). No relapses occurred, with no difference in expanded disability status scale (EDSS) between baseline (4 (2.5–4.5) and 12 months (3.5 (2.5–5.5) p = 0.284). Overall, three new T2 lesions appeared during follow-up. NfL concentration was stable between baseline (7.9 (5.9–45.2) pg/mL) and 12 months (9.1 (5.9–21.3) pg/mL, p = 0.120). IgG concentrations decreased with greater rituximab load (coefficient = −0.439, p = 0.041). IgG deficient patients had greater risk of infections (OR = 6.27, 95% CI = 1.71–22.9, p = 0.005). Conclusion: De-escalating rituximab dose from 1000 to 500 mg/6 months is safe, results in clinical and radiological stability, and does not affect serum NfL over 12 months. Rituximab load negatively influences IgG concentrations, and IgG deficient patients are at higher risk of infections.