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BMC Research Notes Aug 2019Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized...
OBJECTIVE
Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency database of suspected adverse reactions related to medicinal products (EudraVigilance) for fatal adverse events associated with treatment with alemtuzumab (Lemtrada®) for multiple sclerosis. Four independent reviewers with expertise on MS, clinical immunology, infectious diseases and clinical pharmacology reviewed the reports, and scored the likelihood for causality.
RESULTS
We identified nine cases with a probable and one case with a possible causal relationship between alemtuzumab treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of alemtuzumab from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with alemtuzumab occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.
Topics: Adult; Agranulocytosis; Alemtuzumab; Cerebral Hemorrhage; Fatal Outcome; Female; Humans; Immunologic Factors; Listeriosis; Male; Middle Aged; Multiple Organ Failure; Multiple Sclerosis, Relapsing-Remitting; Pneumonia
PubMed: 31405369
DOI: 10.1186/s13104-019-4507-6 -
Current Medical Research and Opinion Aug 2019To estimate the comparative efficacy of cladribine tablets versus alternative disease modifying therapies (DMTs) - fingolimod, natalizumab, alemtuzumab and ocrelizumab... (Meta-Analysis)
Meta-Analysis
Estimating the comparative efficacy of cladribine tablets versus alternative disease modifying treatments in active relapsing-remitting multiple sclerosis: adjusting for patient characteristics using meta-regression and matching-adjusted indirect treatment comparison approaches.
To estimate the comparative efficacy of cladribine tablets versus alternative disease modifying therapies (DMTs) - fingolimod, natalizumab, alemtuzumab and ocrelizumab - in adults with active relapsing-remitting multiple sclerosis (RRMS), using meta-regression to provide subpopulation-specific estimates of drug effect. Additionally, to determine the feasibility of conducting a matching-adjusted indirect comparison (MAIC) to validate the meta-regression results. A published systematic literature review (SLR) identified studies evaluating the efficacy of cladribine tablets and alternative DMTs in the management of active RRMS. A series of meta-regression models were run with adjustment for baseline risk, fitted to data from the intention-to-treat cohorts of trials identified in the SLR. A non-parametric MAIC analysis adjusted for differences between studies by reweighting patient-level data from the index trial to match the mean baseline characteristics reported for trials with only aggregate data. The meta-regression analysis showed significant overlap in credible intervals for the hazard ratios of 6 month confirmed disability progression (CDP-6M) and annualized relapse rate (ARR), with no therapy statistically dominating in terms of efficacy and all therapies estimated to reduce the ARR compared to placebo in all subpopulations. In the MAIC analysis, cladribine tablets showed a reduction in CDP-6M and ARR comparable to alemtuzumab before and after matching. This analysis has demonstrated that cladribine tablets have comparable relative efficacy to other highly efficacious DMTs in active RRMS across all subpopulations, thus validating the comparative effectiveness results from previous network meta-analysis. The MAIC analysis showed that cladribine tablets are comparable in efficacy to alemtuzumab in the treatment of patients with RRMS.
Topics: Cladribine; Disease Progression; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Tablets; Treatment Outcome
PubMed: 30786783
DOI: 10.1080/03007995.2019.1585779