Data provide an update to the post-approval safety profile of cladribine tablets in patients with relapsing MS in reference to COVID-19 infections.
Patients with relapsing multiple sclerosis (MS) treated with 10-mg cladribine (Mavenclad; EMD Serono) tablets were not found to be at greater risk of serious disease and/or severe outcomes when compared with the general population and the MS population. According to findings presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, February 24-26, in West Palm Beach, Florida, the postapproval safety profile of cladribine tablets is consistent with previously published findings from the clinical development program.1
Investigators, led by Gavin Giovannoni, MBBCh, PhD, FCP, FRCP, FRCPath, chair of neurology, Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, University of London, analyzed 503 cases of COVID-19 in patients treated with 10-mg cladribine tablets (3.5-mg/kg cumulative dose over 2 years), updating previously reported findings based on cases reported to the healthcare business of Merck KGaA Global Patient Safety Database. Data were collected as of July 15, 2021, with 316 COVID-19 cases confirmed by tests and 51 cases designated as serious. An additional 6 patients had symptoms consistent with COVID-19 but were not further evaluated following reports of negative PCR tests.
Of the 503 patients that were eligible to be evaluated, a total of 259 (51.5%) had recovered or were recovering at the time of reporting, and 3 patients with suspected COVID-19 had died. Median time to onset of COVID-19 infection from most recent cladribine tablet treatment course was 169 days (range, 0-684) for 314 evaluable patients.
A total of 49,783.5 patient-years of exposure have accrued from 35,688 patients who received cladribine tablets postapproval. For adverse events (AEs) of special interest, adjusted incidences per 100 patient-years were: 0.14 for severe lymphopenia (95% CI, 0.11-0.18); 0.73 for herpes zoster (95% CI, 0.66-0.81), 0.03 for tuberculosis (95% CI, 0.02-0.05), 0.96 for severe infections (95% CI, 0.88-1.05), 0 for progressive multifocal leukoencephalopathy, 0.02 for opportunistic infections (95% CI, 0.01-0.03), 0.22 for malignancies (95% CI, 0.18-0.26), and 0.004 for congenital anomalies (95% CI, 0.001-0.016).
Cases that required hospitalization, were medically significant, or fatal were classified as “serious,” and investigators classified outcomes per usual pharmacovigilance practice. AEs were reported as of July 7, 2021, collected from postapproval sources such as spontaneous individual case safety reports, noninterventional postmarketing studies, and reports from other solicited sources. Included patients had a median age of 41 years and 67.4% were women.
“The safety profile of cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) from the clinical development program for relapsing MS is well characterized,” Giovannoni et al wrote.“Additional real-life safety data have accrued since the approval of cladribine tablets 10 mg in [more than] 80 countries worldwide.”
Giovannoni gave a separate presentation at ACTRIMS Forum 2022, from thephase 4 CLASSIC-MS study (NCT03961204). Reported data suggest that patients who experienced a first clinical demyelinating event and were treated with cladribine over a median 9.5 years of follow-up since last dose experienced long-term sustained efficacy, delayed conversion to clinically definite MS, and fewer second relapses, when compared with nontreated patients.
Since first dose in the respective parent study, 50% (n = 78) of patients exposed to cladribine experienced conversion to clinically definite MS compared with 77.5% (n = 55) of the unexposed group, with median time to conversion for the groups of 3.36 years (range, 0.0-11.1) and 1.21 years (range, 0.0-10.7), respectively. In the cladribine-exposed group, 53.2% of patients remained relapse-free since their last parent study dose compared with 28.2% of the unexposed cohort.
For more coverage of ACTRIMS Forum 2022, click here.