MS Treatment With Tolebrutinib Uninterrupted in Patients With COVID-19 Infection

The study found that all COVID-19 cases were mild to moderate in severity, and all enrolled patients recovered and remained in the study.

A recent long-term extension study of tolebrutinib in those with relapsing multiple sclerosis (RMS) found that cases of COVID-19 infection were mild to moderate, with all patients recovering and remaining in the study. The majority of patients also continued receiving uninterrupted treatment with tolebrutinib while infected with COVID-19.

The data were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, February 24-26, in West Palm Beach, Florida, from the phase 2b trial (NCT03889639), which randomized 130 participants. A total of 129 patients completed the core study and 125 were then enrolled in the long-term extension study (NCT03996291).

Investigators, led by Robert Fox, MD, neurologist, Mellen Center for Multiple Sclerosis, and Vice-Chair for Research, Neurological Institute, Cleveland Clinic, found that 20 (16%) of 125 participants reported a COVID-19 infection as of Sept 6, 2021. This subset of patients had a mean age of 41 years (SD, 9; range, 25-57 years), and cases were logged as mild (n = 11) or moderate (n = 9). Of the moderate cases, 3 were considered serious and 2 patientswere hospitalized, 1 woman (age 55 years) and 1 man (age 57 years). At the cutoff, 1 patient was still recovering, but all the other patients had recovered from their respective COVID-19 infections.

Temporary interruption of tolebrutinib treatment was reported for 4 patients, and the remaining 16 continued use of the therapy throughout their infection. There was 1 woman (56 years old) who had been vaccinated with BNT162b2 (Pfizer/BioNTech) that contracted COVID-19.

“Tolebrutinib is a brain-penetrant Bruton’s tyrosine kinase inhibitor (BTKi) targeting B lymphocytes and myeloid cells (macrophages and microglia), thereby modulating innate and adaptive immunity in the periphery and CNS,” Fox et al wrote. “In the phase 2b trial, tolebrutinib was safe and well tolerated over 12 weeks with dose-dependent reduction in new gadolinium-enhancing T1 and new/enlarging T2 lesions in patients with relapsing multiple sclerosis. Upon completing the study, patients could enter an ongoing long-term extension study to further evaluate the safety and efficacy of tolebrutinib. Given that BTKi is a new class of treatment for MS with immune modulatory characteristics, research is needed to understand the potential impact of BTKi therapy on outcomes of infections such as COVID-19 in patients with RMS.”

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The long-term extension study had 2 parts. During Part A, patients continued double-blind treatment with the same tolebrutinib dose as administered in the core study: 5, 15, 60, or 60 mg per day. During Part B, study participants received open-label tolebrutinib treatment in doses of 60 mg once a day. This dosing regimen is also being tested in the phase 3 trials, Fox et al noted. Demographics, severity, duration and outcomes, and vaccination status were all analyzed for reported COVID-19 cases.

Additional data were presented at ACTRIMS Forum 2022 that suggest health care providers should take risks of severe COVID-19 infection into consideration before starting immunosuppressive disease-modifying therapy (IS-DMT) in patients with multiple sclerosis. Investigators, led by Zhila Maghbooli, PhD, MSc, Neuroscience Institute, Multiple Sclerosis Research Center, Tehran University of Medical Sciences, Iran, evaluated the main risk factors related to adverse clinical outcomes in patients with MS who developed COVID-19 and found that those on IS-DMT were found to have longer hospitalized when compared with those on immunomodulatory-DMT.

For more coverage of ACTRIMS Forum 2022, click here.

REFERENCES
1. Fox R, Li J, Accomando B, Geertsen S, Syen S, Oh J. Characteristics and outcomes of COVID-19 cases from the long-term extension study of tolebrutinib in patients with relapsing MS. Presented at 2022 ACTRIMS Forum; February 24-26; West Palm Beach, FL and Virtual. Poster P126.
2.Maghbooli Z, Aghababaei Y, Hosseinpour H, et al. Association between disease-modifying therapies and adverse clinical outcomes in multiple sclerosis patients with COVID-19 infection. Presented at 2022 ACTRIMS Forum; February 24-26; West Palm Beach, FL and Virtual. Poster P124.