From the Journals

Rare, serious alemtuzumab adverse events emerge

 

Key clinical point: Rare events associated with alemtuzumab are emerging that were not uncovered during clinical trials.

Major finding: Eight cases of acute acalculous cholecystitis formed the basis for its addition to the Warnings and Precautions section of the alemtuzumab label in October 2017.

Study details: Case reports of acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis in two patients, and acute acalculous cholecystitis in eight patients.

Disclosures: None of the reports received funding. Some of the authors had financial ties to the pharmaceutical industry.

Sources: Croteau D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422; Saarela M et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005420; Ferraro D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005417.

View on the News

New findings should encourage vigilance

Clinical trials find most adverse events for a new drug, but postmarketing surveillance is essential to find rare events, even though they may underestimate the frequency of these events because of underreporting.

Other reports suggest the emergence of uncommon infectious complications associated with alemtuzumab, especially Listeria meningitis. Listeria infection can occur within days of alemtuzumab treatment, and the use of preventive sulfamethoxazole-trimethoprim treatment is now advocated in the United Kingdom.

Overall, these adverse events remind clinicians that they must balance the benefits of alemtuzumab, which is highly effective, against its potential risks.

Paolo A. Muraro, MD, PhD is a professor of neurology, neuroimmunology, and immunotherapy at Imperial College London. Neil J. Scolding MD, PhD, is director of the Bristol Institute of Clinical Neurosciences at the University of Bristol (England). Robert J. Fox, MD, is a neurologist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio. All of the authors reported financial relationships with companies marketing MS drugs. Their comments are derived from an editorial accompanying the adverse event reports (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005409).


 

FROM NEUROLOGY

Rare but serious adverse events associated with alemtuzumab treatment of multiple sclerosis (MS) have recently been revealed by postmarketing surveillance, according to three new case reports and series in Neurology.

The complications include acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients.

Photo of a clipboard with the words multiple sclerosis lying next to pills, an injection needle, and stethoscope copyright Zerbor/Thinkstock
Like other MS drugs, alemtuzumab (Lemtrada) mediates inflammation by depleting peripheral blood lymphocytes. It is licensed for the treatment of relapsing MS. In clinical trials, it demonstrated greater efficacy than interferon beta-1a (Lancet. 2012;380[9856]:1819-28) and had an acceptable safety profile, although the trials noted secondary autoimmunity in 30%-35% of patients.

Postmarketing surveillance aims to identify rare and late adverse events that may not be discovered during clinical trials.

The cardiac arrest incident occurred in a 24-year old woman with spinal-onset relapsing-remitting multiple sclerosis (RRMS) during alemtuzumab infusion. She had experienced two clinical relapses and a significant increase in cerebral and spinal MRI lesion load, despite previous treatment with natalizumab (Tysabri). The only striking thing about her medical history was allergic asthma.

On the third day of treatment, she developed severe asymptomatic sinus bradycardia (HR, 38 beats per minute), which resolved with treatment, and clinicians continued the regimen. The following morning, she experienced acute coronary syndrome, which later resolved.

The authors recommend that clinicians treating RRMS patients with alemtuzumab consider a baseline preinfusion ECG and monitoring heart rate at least hourly while infusion is being carried out.

Next Article: