Update on infective complications in patients treated with alemtuzumab for multiple sclerosis: review and meta-analysis of real-world and randomized studies

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.

KEYWORDS:

• Alemtuzumab
• multiple sclerosis
• opportunistic infections
• monoclonal antibodies

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.

Additional information

Funding

This paper was not funded.