— Registry data looks at risks of hospitalization, ICU admission, ventilation
by Judy George, Senior Staff Writer, MedPage Today September 28, 2020
Two reports presented at MS Virtual 2020, a joint meeting of ACTRIMS-ECTRIMS, provided an early look at relationships between anti-CD20 drugs used to treat multiple sclerosis (MS) and COVID-19: registry data from an international consortium and drug company post-marketing data about ocrelizumab (Ocrevus).
Global Registry Data
Registry data from clinicians in 21 countries participating in the Global COVID-19 and MS Data Sharing Initiative suggested MS patients had a higher risk of more severe COVID-19 if they were treated with an anti-CD20 monoclonal antibody than another disease-modifying therapy (DMT) with different mechanisms.
MS patients using anti-CD20 drugs — rituximab (Rituxan), used off-label to treat MS in the U.S., and ocrelizumab, approved for MS in 2017 — were more likely to be hospitalized, admitted to the ICU, or require artificial ventilation than patients treated with other DMTs, reported Steve Simpson-Yap, PhD, MPH, of the University of Melbourne in Australia.
The report also examined whether risk for more severe COVID-19 was higher in MS patients treated with anti-CD20 drugs compared with other DMTs like dimethyl fumarate (Tecfidera) and natalizumab (Tysabri).
Compared with dimethyl fumarate, rituximab was associated with significantly higher risk of hospitalization, ICU admission, and ventilation. Weaker but similar associations were seen for ocrelizumab, and these did not always reach statistical significance.
Compared with natalizumab, pooled data showed the anti-CD20 drugs were associated with higher risks of hospitalization, ICU admission, and ventilation. “This comparison is particularly important because it shows that the associations found with anti-CD20 DMTs were not merely ascertainment bias due to patients having to come to the hospital for infusions” where they may have a greater chance of COVID-19 symptoms being diagnosed, Simpson-Yap told MedPage Today.
“There has been a great deal of discussion in the MS field whether disease-modifying therapies used to treat MS affect the susceptibility to COVID-19 or risk of severe outcomes, and if so, whether there are differences among the DMTs,” noted Jeffrey Cohen, MD, of the Cleveland Clinic of Ohio, who wasn’t involved with the study.
“This large registry study reported that among MS patients with more severe COVID-19 there was increased likelihood of being treated with an anti-CD20 monoclonal antibody relative to other DMTs. Some other studies have reported similar results. Given the mechanism of action and potency of the anti-CD20 monoclonal antibodies, this observation would not be unexpected,” Cohen told MedPage Today.
But he pointed to several limitations. “Other studies have not found this association and have reported no increased risk from anti-CD20 monoclonal antibodies,” Cohen said.
“It’s not 100% clear that the increased risk, if it is real, is due to treatment with an anti-CD20 monoclonal antibody, per se,” he added. “Although the investigators explored this point, it is very difficult to disentangle the treatment used by an individual patient from, for example, their disease characteristics, how many people are treated with the various DMTs in that location, the risk of COVID-19 in that location, etc., all of which might contribute to the association observed.”
Moreover, the report looks at relative risk, while “the absolute risk of COVID-19 and of severe outcomes from it among all MS patients treated with anti-CD20 monoclonal antibodies is quite low,” Cohen said.
The report included aggregated data about 476 MS patients with suspected and 776 with confirmed COVID-19. A total of 313 patients required hospital admission, 76 required ICU admission, 54 required ventilation, and 48 died.
Older age, progressive MS, and higher Expanded Disability Status Scale (EDSS) scores were linked to higher frequencies of severe outcomes.
The researchers calculated adjusted prevalence ratios (aPR) for hospital admission, ICU admission, ventilation, and mortality, adjusting for age, sex, MS type, and EDSS. No associations were observed between DMTs and mortality.
Higher frequencies of the other three outcomes were seen when pooled anti-CD20 DMTs were compared with other DMTs. MS patients on anti-CD20 drugs were 1.5 times more likely to be admitted to the hospital (aPR 1.49), 2.6 times more likely to be admitted to the ICU (aPR 2.55), and 3.1 times more likely to need artificial ventilation (aPR 3.05, P<0.05 for all) than those using other drugs.