The onset of the COVID-19 pandemic affected all aspects of medical care, including the management of multiple sclerosis (MS).
“There was some concern about the disease itself increasing the susceptibility, or the risk of complications, from COVID-19,” Gabriel Pardo, MD, director of the Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, told MedPage Today. “And by extension there were concerns about the different medications we use because they have an effect on the immune system.”
“So there were a lot of different recommendations given by institutions and organizations,” said Pardo. However, as described in these guidelines published by the Consortium of Multiple Sclerosis Centers, the differences among these recommendations created some confusion.
The problem, according to Joseph Berger, MD, an MS specialist at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, is “that we really had no hard data on how the disease itself would be affected by MS, and how MS would be affected by COVID. And more importantly, how people on disease-modifying therapies (DMTs) would respond to COVID, and whether it would increase the morbidity and mortality of COVID.”
One response, Pardo explained, was a concerted effort on the part of the MS field to set up registries of patients living with MS who were infected with COVID-19. For example, COViMS (COVID-19 Infections in MS & Related Diseases) is a joint effort by the National MS Society, Consortium of MS Centers, and Multiple Sclerosis Society of Canada to capture information on outcomes of people with MS and other central nervous system demyelinating diseases who have developed COVID-19.
“So far, and this is an evolving concept, it has been very reassuring that we do not have clear evidence that our MS patients are at increased risk for developing the infection or developing complications,” said Pardo. “They seem to have the same risk as the general population, with comorbidities playing the same sort of role.”
In a study published in the Lancet Neurology, Italian researchers evaluated 232 MS patients who had either tested positive for COVID-19 or were suspected of having the infection. Most of these patients (96%) had either mild or no pneumonia.
The infection was considered severe in four people, and critical (defined as respiratory failure, septic shock, and multiple organ dysfunction or failure, and were hospitalized in an intensive care unit) in six patients. Of those six critical patients, one recovered and five (2%) died. Those patients tended to have comorbidities, higher disability, and/or were age 50 or older.
And a French cohort study of 347 patients with MS published in JAMA Neurology found that risk factors for severe forms of COVID-19 were neurological disability, age, and obesity (with patients with high Expanded Disability Status Scale (EDSS) and older age at highest risk of severe COVID-19), but that there was no association between DMT exposure and COVID-19 severity.
Berger, along with UPenn colleagues Rachel Brandstadter, MD, and Amit Bar-Or, MD, published a review of the current state of knowledge regarding the effect of MS DMTs on COVID-19 illness.
Anecdotal reports suggested that “patients with MS, including those on commonly used DMTs, are at no higher risk of contracting symptomatic SARS-CoV-2 viral infection, nor at a higher risk of severe COVID-19 complications, compared with the population at large,” the group wrote.
Berger said that there was particular concern about drugs such as alemtuzumab (Lemtrada) or cladribine (Mavenclad), which are classified as immune reconstitution therapies. “But with respect to other [DMTs] we didn’t think there was likely to be a significant problem,” Berger told MedPage Today. “And our own practice was not to change anything when managing these patients. We have kept our own registry and our initial thoughts have been borne out, which is that there does not appear to be a significant effect either on morbidity or mortality with respect to the disease-modifying therapies we employ — and that includes cladribine. We have people that we have started on cladribine, and have been on cladribine, and have developed COVID, and they’ve done well, and the large registries seem to bear this out.”
“The people who have had a significant problem with respect to COVID-19, and who have MS, are, for the most part, older individuals, with multiple comorbidities that increase the risk of COVID morbidity and mortality, and quite often are not on any therapy whatsoever, and are disabled as a consequence of their disease,” he added. Most have EDSS scores of 6 or more, he noted, meaning their ambulation is affected.
Berger suggested that some of these DMTs could even have a “salutary” effect by limiting the aggressive immune response that causes the most severe complications associated with COVID-19. For example, fingolimod (Gilenya) is being tested as a treatment for acute respiratory distress in COVID patients.
In their report, Berger and his colleagues recommended that most patients with MS continue on their DMT, “particularly those on platform therapy for whom the risk of SARS-CoV-2 infection and COVID-19 is minimal.” They added that treatment decisions should be tailored to individual patients, particularly for those with increased risk of either acquiring infection or with serious COVID-19 complications.
In its treatment guidelines, the National Multiple Sclerosis Society recommended that DMT decisions should be individualized and made collaboratively between MS patients and their care providers; that discussions between patient and provider should include a consideration of disease factors, risks and benefits of the DMT, and risks associated with COVID-19; and that persons with MS currently taking DMTs should continue treatment.
One question that remains to be answered, said Pardo, is how patients with MS will respond to a potential vaccine. “Will the fact that they are on different medications affect the immune system and blunt the ability to mount an appropriate response to the vaccine, or decrease it?” he said. “We don’t know that quite yet.”
Berger agreed that diminished vaccine response might occur “with some of the drugs we use like the anti-CD20 monoclonal antibodies, and perhaps with others as well. It may be that those in our MS population on these drugs might need more than one dose of the vaccine, and that the antibody response will need to be monitored to ensure that it is adequate.”
He also noted that clinicians have traditionally advised MS patients on DMTs to avoid live virus vaccines of any kind. But, he said, “it looks like there are very few live virus vaccines in development, and those under development in the U.S., to the best of my understanding, are not live virus vaccines. So any of those vaccines should be fine in the MS population regardless of the disease-modifying therapy they are on.”
Berger serves as a consultant and/or on the PML adjudication committees of Novartis and Takeda/Millennium. He also serves on the scientific advisory board of Excision Bio and Inhibikase. He is chair of the Data Safety Monitoring Board for MAPI.
Pardo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities for Alexion, Biogen, Celgene, EMD Serono, Roche/Genentech, Novartis, and Sanofi Genzyme.