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 2 years) were lacking.ConclusionBased on the largest possible evidence base, including previously unpublished data, our systematic review shows substantial evidence gaps for DMTs in highly active RRMS.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

BackgroundTo update previous work assessing the relative efficacy and safety of cladribine tablets compared to currently approved disease-modifying treatments (DMTs) in patients with active relapsing-remitting multiple sclerosis (RRMS), using systematic literature review (SLR) and network meta-analysis (NMA).MethodsSystematic literature searches were conducted in MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases to identify English-language publications of relevant studies of approved DMTs for RRMS. Searches were conducted from database inception to January 2017, and then further updated from January 2017 to September 2022. Conference websites and trial registries were also searched. NMA considered the effects of DMTs on annualized relapse rate (ARR), confirmed disease progression (CDP), proportion relapse-free (RF), and safety.ResultsOf 21,181 unique articles retrieved and screened, 66 studies met the inclusion criteria and had their data extracted, including 17 new studies since the previous review; of these, 57 studies assessing 20 DMTs contributed to the NMA. In patients with active RRMS, cladribine tablets were associated with a significant 58% reduction in ARR versus placebo; cladribine tablets were similar or significantly better than other DMT regimens. For 6-month CDP, improvements with cladribine tablets were significantly greater than those of placebo, with no comparator DMT demonstrating significantly better results. For both efficacy endpoints, cladribine tablets ranked sixth among DMTs, behind ofatumumab, ublituximab, alemtuzumab, natalizumab, and ocrelizumab. The overall adverse event risk for cladribine tablets was statistically comparable to all other oral DMTs and both interferon beta-1a regimens.ConclusionsIn this updated SLR and NMA, cladribine tablets remain a comparatively effective and safe alternative to other currently approved DMTs in populations of patients with active RRMS.

Abstract licence: CC BY-NC-ND