Ofatumumab 20mg/0.4ml solution for injection pre-filled disposable devices

BackgroundComparative assessments of all available disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting multiple sclerosis (RRMS) are lacking, even though some of these DMTs are restricted to this MS subpopulation. We therefore aimed to compare DMTs in patients with highly active RRMS using re-analyses of individual patient data (IPD) provided by study sponsors.MethodsWe searched for randomised controlled trials (RCTs) that included adult patients with RRMS and directly compared alemtuzumab, cladribine, dimethyl fumarate, fingolimod, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod and teriflunomide, or compared these DMTs with other drugs or placebo. Re-analyses of IPD for subpopulations of patients with high disease activity despite previous DMT were included in network meta-analyses (NMAs). As there is no widely accepted definition of high disease activity in RRMS, criteria were chosen to cover as wide a range of definitions as possible, while being sufficiently similar across studies.ResultsWe identified 14 relevant RCTs, including only 3 head-to-head comparisons of DMTs, and no relevant studies on natalizumab. All studies were pivotal studies for approval. The available re-analyses of IPD did not allow comprehensive NMAs. The main reasons for this were the overall paucity of RCTs, especially head-to-head comparisons, and a high risk of bias. In addition, data on patient-relevant outcomes and long-term follow-up (> 2 years) were lacking.ConclusionBased on the largest possible evidence base, including previously unpublished data, our systematic review shows substantial evidence gaps for DMTs in highly active RRMS. This indicates a need for further research beyond regulatory requirements.Trial registrationClinical trial number: not applicable.

Abstract licence: CC BY

BackgroundMultiple treatments have demonstrated efficacy in preventing brain volume loss (BVL) in randomized controlled trials (RCTs) for multiple sclerosis (MS). However, assessing their relative effectiveness remains challenging due to limited head-to-head comparisons. Additionally, the relationship between treatment effects on BVL and disability accumulation is not established for newer therapies. This study aimed to compare the efficacy of approved disease-modifying therapies (DMTs) in reducing BVL in MS and to investigate the association between treatment effects on BVL and disability accumulation.MethodsIn this systematic review and network meta-analysis, we included all RCTs enrolling adults with MS that evaluated FDA-approved DMTs and reported BVL outcomes over at least one year. We searched PubMed, Embase, and Cochrane from inception to September 2024. Following PRISMA guidelines, two reviewers independently extracted data on BVL, MRI lesion activity, and disability progression. We conducted a mixed-effects network meta-analysis with placebo as the reference group. Meta-regression analyses examined the association between treatment effects on BVL and disability progression, adjusting for MRI lesion activity.The primary outcome was BVL. Secondary outcomes included MRI lesion accumulation and risk of confirmed disability progression. Effect sizes were reported as the ratio of means (ROM) and hazard ratios (HRs), with 95% confidence intervals (CIs). This study is registered with PROSPERO (CRD420251034936).FindingsWe included 33 RCTs evaluating 16 DMTs and 26,247 patients. Eight DMTs significantly reduced BVL compared to placebo, including ponesimod (ROM = 0.52; 95%-CI: 0.35-0.77), ofatumumab (ROM = 0.58; 95%-CI: 0.40-0.83), alemtuzumab (ROM = 0.63; 95%-CI: 0.49-0.83), teriflunomide (ROM = 0.71; 95%-CI: 0.52-0.97), ozanimod (ROM = 0.74; 95%-CI: 0.56-0.98), natalizumab (ROM = 0.77; 95%-CI: 0.61-0.96), siponimod (ROM = 0.77; 95%-CI: 0.60-0.98), and fingolimod (ROM = 0.83; 95%-CI: 0.71-0.96). The treatment effect on BVL was associated with the treatment effect on disability accumulation (β = 0.466; p = 0.008), and this association remained significant independently of the treatment effect on MRI activity (β = 0.422; p = 0.005).InterpretationSeveral DMTs-including newer therapies-significantly reduce BVL, and this effect correlates with reduced disability accumulation. These findings support BVL as a meaningful treatment target in MS.FundingNone.

Abstract licence: CC BY

BackgroundAnti-metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare autoimmune disease affecting cerebellar Purkinje cells. Only thirty-nine cases have been reported globally, with inconsistent documentation of treatments and outcomes. A systematic review is needed to identify prognostic factors and expand clinical understanding and treatment options.MethodsObservational follow-up data of anti-mGluR1 encephalitis cases were collected. All anti-mGluR1 encephalitis cases published in the PubMed and Google Scholar databases in English before November 1, 2024 were included. Clinical information and possible predictive factors from both current and previously reported cases were statistically analyzed.ResultsWe present a case of anti-mGluR1 encephalitis successfully treated with ofatumumab. During the patient's initial episode, she partially recovered after first-line treatment. She experienced a relapse 6 months later and was treated with ofatumumab, resulting in complete recovery. Forty cases of anti-mGluR1 encephalitis, including our case, were summarized. The prevalence was similar between men and women, with 50% of patients aged 40-59 years. The most common clinical manifestations were ataxia and dysarthria. Cerebrospinal fluid analysis showed normal white blood cell count and IgG index in 37.1% of patients. Almost half of the patients (48.6%) exhibited cerebellar atrophy on cerebral MRI scans at initial presentation or during follow-up. Only 25% of patients recovered completely. According to the modified Rankin Scale (mRS) scores at the last follow-up, patients with poor outcome (n = 13, 32.5%) had a lower proportion of first-line immunotherapy (62%, P = 0.017) and a longer follow-up time (median 36 months, P = 0.038).ConclusionThe peak incidence of anti-mGluR1 encephalitis occurs between ages of 40-59 years. More than one-third of patients have normal cell counts and IgG index in the cerebrospinal fluid. Therefore, patients suspected of having this encephalitis should be tested for the presence of anti-mGluR1 antibodies in serum and cerebrospinal fluid. Notably, the first-line immunotherapy may be a critical factor influencing clinical outcomes.

Abstract licence: CC BY

IntroductionIn relapsing-remitting multiple sclerosis (RRMS), conventional immunomodulatory and immunosuppressive therapies are widely used. However, in many cases, optimal control of inflammatory activity and disease progression is not achieved, which has led to the use of biological drugs such as monoclonal antibodies that act specifically on key components of the immune system. The aim was to evaluate the efficacy and safety of monoclonal antibodies compared to other drugs or placebo in adult patients with RRMS.MethodsA systematic review was performed based on randomized, double-blind, phase III controlled clinical trials published between 2012 and 2025 in the PubMed, Cochrane Library, and Web of Science databases, assessing efficacy and safety in adult patients with RRMS. The review was carried out following the PICO methodology and PRISMA guidelines.ResultsA total of 11 studies were included, evaluating 5 monoclonal antibodies: alemtuzumab, daclizumab, ocrelizumab, ofatumumab, and ublituximab. These therapies showed superior efficacy compared to conventional treatments in reducing the annual relapse rate, MRI inflammatory activity and MRI activity, particularly in patients with highly active disease. However, effects on disability progression were heterogeneous across trials and not consistently significant. In addition, decreases in biomarkers of axonal damage were observed. Nevertheless, relevant adverse effects were identified, including infections, autoimmune reactions, hepatic and cutaneous toxicity, whose incidence varies depending on the drug, requiring close clinical monitoring.ConclusionsMonoclonal antibodies are an effective option in RRMS, with clinical and radiological benefits superior to those of conventional treatments. Their use requires individualized assessment and close follow-up due to the risk of adverse effects, especially in high-risk patients.

Abstract licence: CC BY

BackgroundDisease-modifying therapies (DMTs) have transformed multiple sclerosis (MS) care but are associated with substantial costs. Among high-efficacy DMTs, anti-CD20 antibodies are widely used, yet their economic value, particularly compared with different classes of DMTs, has not been comprehensively synthesized.ObjectiveTo systematically review evidence on the cost-effectiveness of anti-CD20 antibodies compared with other DMTs or best supportive care (BSC) in MS.Data sources and methodsWe searched PubMed, Embase, Web of Science, and International Network of Agencies for Health Technology Assessment (July 2025) for cost-effectiveness analyses comparing rituximab, ocrelizumab, ofatumumab, or ublituximab with other DMTs or BSC. Two reviewers independently screened studies, extracted data, and assessed reporting quality using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. All costs were converted to 2024 US dollars and adjusted for inflation.ResultsOf 92 records screened, 20 studies met inclusion criteria. Analyses were conducted in diverse but mostly high-income regions, most commonly using Markov models with long time horizons. Anti-CD20 antibodies were dominant (more effective, less costly) or cost-effective in the majority of studies, particularly when compared with platform therapies. In contrast, comparisons with other high-efficacy DMTs yielded more heterogeneous results, with immune reconstitution therapies more cost-effective in several studies. Reporting quality was generally high, although patient involvement, assessment of heterogeneity, and a health economic analysis plan were rarely addressed.ConclusionThese findings support the use of anti-CD20 antibodies as an economically reasonable option in many healthcare settings, particularly when compared with platform therapies, while underscoring that cost-effectiveness relative to other high-efficacy treatments is context-dependent. The lack of data from low- and middle-income countries and limited transparency in Health Technology Assessment reports represent major limitations. Future research should prioritize context-specific evaluations and promote full disclosure of economic data to strengthen the evidence base for clinically and economically informed reimbursement decisions in MS.Trial registrationThe study was prospectively registered with PROSPERO (ID: CRD420251109958).

Abstract licence: CC BY-NC

Several clinical trials with anti-CD20 antibodies have successfully treated Acute Lymphoblastic Leukemia. Nevertheless, systematic comparisons between different anti-CD20 antibody trials are rare, and a comprehensive evaluation of their efficacy and safety has yet to be performed. The purpose of this systematic review and meta-analysis was to assess the efficacy and safety of anti-CD20 antibodies in the treatment of acute lymphoblastic leukemia and to guide clinical decision-making regarding the use of anti-CD20 antibody therapy. According to the PRISMA guidelines, Embase, Cochrane Library, PubMed, Web of Science, and ClinicalTrials.gov were searched for clinical trials conducted up to November 1, 2024, for the evaluation of anti-CD20 antibodies (rituximab, obinutuzumab, and ofatumumab) and corresponding controls. After screening the literature and extracting data, study quality was assessed using the Cochrane ROB 2 tool (RCTs) and the Newcastle-Ottawa Scale (cohorts). Heterogeneity was assessed using the I² test. Based on the results of the heterogeneity test, meta-analysis was performed in RevMan 5.4 software with either a random-effects model or a fixed-effects model. We combined data from eight studies (n = 1330 patients, including two RCTs and six cohorts). Meta-analysis showed that anti-CD20 monoclonal antibodies significantly improved overall survival (OR = 1.89, 95% CI: 1.21-2.95, p = 0.005) and event-free survival [OR = 1.68, 95% CI: 1.32-2.14, p 1-year follow-up, and increased complete remission rates (p < 0.05). No significant differences were observed in common adverse events between groups. Subgroup analyses by study type did not alter these conclusions. Overall, anti-CD20 antibody therapy was more efficacious than the corresponding control and did not increase the incidence of grade 3-4 adverse events. Ofatumumab may be a more effective anti-CD20 antibody for the treatment of ALL.

Abstract licence: CC BY-NC

Rituximab is a chimeric anti-CD20 monoclonal antibody that is becoming increasingly used in multiple sclerosis. In rare cases, rituximab may induce a delayed immune-mediated reaction such as rituximab-induced serum sickness. We report the case of a 49-year-old woman with multiple sclerosis who developed rituximab-induced serum sickness characterized by fever, diffuse rash, lymphadenopathy, and arthralgia nine days after her first rituximab infusion. We reviewed the number of cases in a literature review, discussing their characteristics and mechanisms and the implications for using alternative anti-CD20 monoclonal antibodies such as ocrelizumab or ofatumumab for the management of multiple sclerosis.

Abstract licence: CC BY