ABSTRACT
Objective
We aimed to systematically assess the pooled prevalence of infective complications in randomized controlled trials (RCTs) and real-world studies (RWSs) investigating alemtuzumab treatment in multiple sclerosis (MS), also looking at selected infections and their severity.
Methods
We included in the analysis RCTs and RWSs investigating the use of alemtuzumab in MS in which infective complications were reported, as well as case reports of rare infections. We conducted a meta-analysis of proportions and a random effect model meta-regression to investigate heterogeneity.
Results
The pooled prevalence of infective complications in alemtuzumab treated MS patients is 24%. The most common reported infections are respiratory tract infections (47%) and the most part of the infections are mild-to-moderate (85%). Severe infections account for 6% of the total estimate. We found first-time-reported cases of invasive aspergillosis, hepatitis E virus infection, EBV hepatitis, and cerebral toxoplasmosis. The prevalence of infections is higher in studies conducted before 2009, and in studies with higher proportion of male participants.
Conclusions
Clinicians should be aware that the prevalence of serious infections during alemtuzumab can be higher than expected from RCTs. Peculiar opportunistic infections should be considered when evaluating a patient treated with alemtuzumab who develops signs of infection.
Notes on contribution
Buonomo A.R., Literature search, study selection
Viceconte G., Literature search, study selection, statistical analysis
Zappulo E., Data extraction
Maraolo A.E., Statistical analysis, quality assessment of the included studies
Russo C.V., Data extraction, revised the manuscript for intellectual content
Carotenuto A., quality assessment of the included studies, revised the manuscript for intellectual content
Moccia M., revised the manuscript for intellectual content and statistical quality
Gentile I., revised the manuscript for intellectual content
Article Highlights
The pooled prevalence of infective complications in patients treated with alemtuzumab for multiple sclerosis is 24%.
Severe infections account for 6% of the total, higher than estimates from clinical trials.
The most common reported infections are respiratory tract infections (47%) and the most part of the infections are mild-to-moderate (85%).
The prevalence of infections is higher in studies conducted before 2009, and in studies with higher proportion of male participants.
We found first-time-reported cases of invasive aspergillosis, hepatitis E virus infection, EBV hepatitis and cerebral toxoplasmosis.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2021.1942454.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.