New MS Drug Does Not Appear to Increase COVID Severity

Multiple sclerosis (MS) patients treated with ofatumumab (Kesimpta) in an open-label extension study had non-serious cases of COVID-19 and recovered relatively quickly, researchers reported.

Of 139 relapsing-remitting MS patients with COVID-19 in the ALITHIOS study, 94% had mild or moderate cases and 96% recovered within 20 days, reported Anne Cross, MD, of Washington University in St. Louis, at the 2021 Consortium of Multiple Sclerosis Centers meeting.

Ten people were hospitalized and one person died. There was no evidence that COVID-19 incidence or severe outcomes were higher in ofatumumab-treated people compared with the general population or with other MS patients, Cross said.

Ofatumumab, an anti-CD20 drug, was approved in August 2020 for adult MS patients with clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Like ocrelizumab (Ocrevus), which was approved in 2017 for relapsing and primary progressive MS, and rituximab (Rituxan), which is used off-label in MS, ofatumumab results in B cell depletion. Ocrelizumab and rituximab are infused treatments, while ofatumumab is given by monthly subcutaneous injection.

Large studies have linked ocrelizumab and rituximab with worse COVID-19 outcomes for people with MS. “It’s important to highlight the differences between those real-world studies and the current ofatumumab study,” noted Riley Bove, MD, of the University of California, San Francisco, who wasn’t involved with the study.

“The current study followed mainly patients in ALITHIOS, an open-label extension study following patients enrolled in the pivotal trials for ofatumumab. The average time on drug was 2.2 years at the time of the infection, and the mean age of the patients was 37.7 years,” Bove told MedPage Today.

“In the real world, many patients on B cell depleting therapies are older, may have more comorbidities than patients who are enrolled in clinical trials, and are on treatment for longer,” she pointed out. “Given the timeline of approval of ofatumumab, the real-world studies mainly examined patients whose B cells were depleted by rituximab or ocrelizumab.”

“Therefore, we should be careful about interpreting risk of severity of infection in the general population of B cell depleted patients, of even just ofatumumab-treated patients, based on the current findings,” Bove said. “In fact, IgG [immunoglobulin G] levels tend to decline over time in patients who are B cell depleted, and in the current study all patients still had normal IgG levels.”

In their study, Cross and co-authors reviewed COVID-19 cases that occurred in the ALITHIOS open-label extension trial with a data cutoff of January 29, 2021. They also looked at post-marketing reports of COVID-19 cases in patients on ofatumumab until January 31. “Cases were defined as confirmed by laboratory confirmation, or suspected COVID-19 with signs and symptoms but no laboratory confirmation,” Cross said in her presentation.

As of data cutoff, 139 of 1,703 patients (8.2%) in ALITHIOS reported COVID: 115 were confirmed cases and 24 were suspected. Mean baseline age for these patients was about 38 and most (64%) were female.

Of the 115 patients with confirmed COVID-19, the time between the first dose of ofatumumab and COVID onset was 2.3 years. Twelve people had pneumonia, eight were hospitalized, and one patient, a 48-year-old woman, died.

Twenty-two patients in ALITHIOS interrupted their ofatumumab treatment but no one discontinued the drug. All 139 COVID-19 cases had IgG levels above the lower limit of normal before or during the period they had COVID.

Similar findings were seen in post-marketing reports of 26 confirmed and two suspected COVID cases. Most cases were mild or moderate and no one died.

“Immune response to SARS-CoV-2 was assessed independently of this study in three cases with mild confirmed COVID-19,” Cross noted. “No antibody responses were observed in any of the three. However, T cell immune responses against SARS-CoV-2 were observed in all three patients.”

It’s important to note the cutoff for data in this study was in January 2021, Bove observed.

“At that time, it’s likely most patients were unvaccinated,” she said. “Given recent data suggesting that patients who are B cell depleted can still mount a robust T cell response to COVID-19 vaccines, we hope the outcomes in vaccine-breakthrough COVID might be even better than the outcomes reported here.”