Ublituximab 150mg/6ml solution for infusion vials

Background: Relapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA). Methods: The SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA). Results: We included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64-1.62)), natalizumab (RR 0.99 (0.59-1.65)), alemtuzumab (RR 0.86 (0.51-1.46)), and ocrelizumab (RR 0.75 (0.44-1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49-1.92)), natalizumab (HR 1.13 (0.53-2.40)), alemtuzumab (HR 1.25 (0.56-2.81)), and ocrelizumab (HR 1.29 (0.57-2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab. Conclusions: Results of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.

Abstract licence: CC BY 4.0

Context Multiple sclerosis (MS) is a devastating autoimmune neurodegenerative disease, for which disease-modifying drugs (DMDs) have been associated with secondary autoimmune dermatological disorders. Objectives This systematic review of case reports seeks to examine documented case reports involving biological medications utilized in managing MS attacks and disease progression that correlate with such dermatological complications. Evidence Acquisition A systematic search was conducted in the Google Scholar, Scopus, and PubMed databases for studies published until January 2024. The search strategy employed combinations of keywords such as “multiple sclerosis” with specific biological agents (“Natalizumab” OR “Ocrelizumab” OR “Rituximab” OR “Alemtuzumab” OR “Ofatumumab” OR “Ublituximab”) and “case report”, incorporating relevant Medical Subject Headings (MeSH) terms. All articles, if full texts were available, on case reports and case series of autoimmune dermatological complications of biological medication of MS were analyzed. The quality of the case reports was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist. Results A total of 19 articles fulfilled the inclusion criteria and were included in this review. The highest frequency of secondary autoimmune complications was documented with alemtuzumab administration, whereas rituximab demonstrated the lowest incidence of dermal autoimmune manifestations in MS patients. Conclusions The employed injectable MS immunotherapies demonstrate various autoimmune adverse reactions that have been documented across numerous case reports. This review examines different categories of secondary autoimmune complications and explores the theoretical mechanisms underlying their development.

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.

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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

BackgroundMultiple Sclerosis treatment with B-cell targeted therapies may be associated with an increased incidence of headache. We aimed to find and compare the association of B-cell targeted therapies with the incidence of headache in patients with Multiple Sclerosis.MethodsIn a systematic based approach, the following databases were searched from inception until the 6th of June 2020: Pubmed/MEDLINE, ClinicalTrials.gov, EU Clinical Trials Register. Only randomized clinical trials (RCTs) enrolling patients with Multiple Sclerosis comparing B-cell targeted therapies (Rituximab, Ocrelizumab, Ofatumumab, Ublituximab or Cladribine) with placebo were selected for the systematic review and further meta-analysis. PRISMA guidelines were followed at all stages of the systematic review. The primary outcome was an all-cause headache of B-cell targeting therapy in patients with Multiple Sclerosis.ResultsNine RCTs were included. Compared with placebo, treatment with B-cell targeting therapies revealed a trend in headache risk, but it was not statistically significant (Relative Risk 1.12 [95% Confidence Interval 0.96-1.30]; p = 0.15; I2 = 9.32%). Surprisingly, in a sub-group analysis, Cladribine was statistically significant for an increase in headache risk (RR 1.20 [95% CI 1.006-1.42]; p = 0.042; I2 = 0%; 3 studies with 2107 participants).ConclusionsEven though a trend is shown, B-cell targeted therapies do not correlate with an increased incidence of headache as an adverse effect. Sub-analyses revealed a significant association between Cladribine alone and an increased incidence of headache. Whereas a purinergic signaling cascade is proposed as a mechanism of action, further research is needed to unravel the underlying pathogenetic mechanism of headache induction and establish headache prevention strategies.

Abstract licence: CC BY