Disease-modifying therapy
Immunomodulators and immunosuppressant therapy slow the progression of the disease in relapsing-remitting multiple sclerosis (1). Patients with progressive forms of the disease are also treated to an increasing extent, but derive generally less benefit (2). Until recently, the majority of patients started with drugs that have a relatively limited effect and low risk (interferons, glatiramer acetate and teriflunomide), and switched to more effective therapy (fingolimod, natalizumab, cladribine, rituximab, alemtuzumab) if they suffered new relapses or an MRI scan revealed new signs of disease activity. Because prompt commencement of potent therapy has the optimal effect on the long-term prognosis (1), and because the risk associated with several of these drugs appears to be relatively low, potent drugs are now often used as initial treatment.
Glatiramer acetate and interferon-β normally cause little or no immunosuppression. With the partial exception of natalizumab, which specifically inhibits migration of lymphocytes from the blood to the central nervous system, all more potent MS therapies are immunosuppressant (Table 1). However, the degree of immunosuppression varies across drugs and over time, and in most patients is limited or moderate. Autologous haematopoietic stem cell transplantation (HSCT) and alemtuzumab cause immediate, almost full depletion of circulating T and B cells and pronounced immunosuppression, which is strongest in stem cell therapy where other immune cells are also affected.
Table 1
Important properties of different therapeutic options used for multiple sclerosis under the COVID-19 pandemic. The table represents the authors' assessments in mid-April 2020, based on the data presented in the article.
| |
Efficacy against multiple sclerosis |
Immunosuppression due to the therapy |
Rebound disease activity on cessation |
Start therapy under COVID-19 pandemic |
Continue therapy under COVID-19 pandemic |
Need for blood tests during treatment |
| Glatiramer acetate |
Limited |
No |
No |
OK |
OK |
No |
| Interferons |
Limited |
No |
No |
OK |
OK |
Rare |
| Teriflunomide |
Limited |
Limited |
No |
OK |
OK (watch out for granulocytopenia) |
Frequent |
| Dimethyl fumarate |
Medium |
Limited |
No |
OK |
OK (watch out for lymphopenia) |
Rare |
| Fingolimod |
Medium/high |
Moderate |
Yes |
Consider alternative |
OK (watch out for lymphopenia) |
Rare |
| Natalizumab |
High |
Limited |
Yes |
OK (JCV negative) |
OK, intervals can be extended |
Rare |
| Rituximab Ocrelizumab |
High |
Prolonged moderate |
No |
Consider alternative |
Consider postponing |
Rare |
| Cladribine |
High |
Prolonged moderate |
No |
Consider alternative |
Consider postponing |
Rare |
| Alemtuzumab |
High |
High, waning |
No |
No |
Consider postponing |
Frequent |
| Autologous haematopoietic cell transplantation |
High |
Very strong, declining |
No |
No |
Not relevant |
Frequent initially |
Immunosuppression declines gradually, so that the immune system of the great majority is fully restored after a few years. Cladribine also inhibits both T and B cells for a long time, but the effect is less pronounced and the immune system will be gradually reconstituted. Antibodies against B cells (rituximab and ocrelizumab) have little effect on T cells and plasma cells and therefore cause less pronounced acute immunosuppression. As the drugs are normally administered at six month intervals, however, the immune system is reconstituted to a lesser degree, and the incidence of severe infections appears to be higher than with natalizumab (3).