Alemtuzumab 30mg/1ml solution for infusion vials

BACKGROUND: Alemtuzumab (ALEM), an immune reconstitution therapy for multiple sclerosis (MS), has been associated with an increased risk of secondary autoimmune diseases, including Graves’ disease (GD). Graves’ orbitopathy following ALEM (GO-f-ALEM) is a rare, but relevant manifestation. GO-f-ALEM epidemiology and clinical course are still poorly characterized. MAIN BODY: The first aim of this paper was to perform a systematic review of published evidence of GO-f-ALEM in patients with MS, focusing on clinical features and management. Second aim was to integrate and compare literature data with real-world pharmacovigilance reports and institutional cases. A systematic review of published literature databases (PubMed, Embase, Scopus) from inception to December 2024 was performed according to PRISMA guidelines. A total of 42 published GO-f-ALEM cases in MS patients were identified. In parallel, as additional sources of data, which were not included in the systematic review analysis, 272 cases were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, and three institutional cases were described and analysed. GO-f-ALEM occurred more frequently in middle-aged adults (mean age 41 years old), with female predominance (60%) and a high rate of smoking (60%). GO generally occurred after 2–5 years from ALEM initiation. Fluctuating thyroid function and thyrotropin receptor antibody (TRAb) levels were commonly observed, with frequent need for definitive thyroid treatment (surgery or radioactive iodine - RAI). GO presentation was heterogeneous - from mild to sight-threatening forms - and mainly manifesting with lid retraction, proptosis, and diplopia. Concurrently, pharmacovigilance data from FAERS identified almost 300 reports of eye disorders potentially consistent with GO, thus suggesting under-diagnosis or under-reporting prevalence in literature. Institutional cases confirmed the potential for sight-threatening GO with dysthyroid optic neuropathy. CONCLUSIONS: Our data suggest that GO-f-ALEM is an underrecognized disorder within the spectrum of ALEM-induced autoimmunity, with peculiar features, as suggested by clinical and immunological observations and simultaneously by pharmacovigilance reports. Routine ophthalmic monitoring and standardized GO classification are essential for diagnosis and follow-up. Prospective studies are warranted to better define its epidemiology and guide optimised management strategies.

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ObjectiveTo comparatively evaluate the efficacy and safety of induction therapies in solid organ transplantation (SOT) using a Bayesian network meta-analysis (NMA).MethodsRandomized controlled trials (RCTs) assessing induction therapies were systematically identified across major databases (up to November 20, 2024). The screening, data extraction, and risk of bias (ROB) assessment were independently conducted by two reviewers through standardized tools. Bayesian NMA synthesized outcomes, including rejection, graft/overall survival, and infection rates.ResultsSixty-eight RCTs (9,626 patients) evaluating 12 therapies were included. Surface Under the Cumulative Ranking Area (SUCRA) probabilities identified alemtuzumab as the most effective agent for reducing rejection rates (93.9%), followed by antilymphocyte globulin (ALG, 87.0%) and belimumab (77.0%). For graft survival, OKT3 ranked highest (87.9%), with subsequent superiority for ALG (83.5%) and alemtuzumab (75.6%). Basiliximab demonstrated the highest overall survival benefit (88.0%), outperforming rabbit antithymocyte globulin (rATG, 82.1%) and inolimomab (70.3%). Belimumab showed the greatest infection risk reduction (94.4%), surpassing alemtuzumab (80.0%) and basiliximab (74.5%).ConclusionAlemtuzumab emerged as the optimal therapy for minimizing rejection, while OKT3 and basiliximab were superior for graft and overall survival, respectively. Belimumab exhibited the strongest potential for reducing incidence of infection. These findings highlight therapy-specific advantages for optimizing SOT outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD42025634120.

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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.

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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.

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