Enteroviral infections with antiCD20 therapies—A class effect?

Anti-CD20-directed B-cell depletion therapy has become a highly effective standard treatment for relapsing and progressive MS. The most significant side effect is an increased susceptibility to infection, which is mediated in part by the development of hypogammaglobulinaemia. ¹ Opportunistic infections require particular attention, and in this context, the frequently reported occurrence of fatal enteroviral encephalitis under rituximab and ocrelizumab is of particular note. ² It is noteworthy that in many cases, normal IgG levels were present, yet an IgM deficiency was almost universally observed.

The findings from the registration studies demonstrated that the occurrence of hypogammaglobulinaemia in ofatumumab patients does not appear to be a frequent phenomenon. ³ Consequently, it was hypothesised that the adoption of this treatment would result in a reduced incidence of recurrent (and opportunistic) infections. However, analysis of real-world data suggests that the effects are similar to those seen with the older agents. ⁴ Furthermore, new case reports also include cases of enteroviral encephalitis during ofatumumab therapy. ⁵ Consequently, a class effect of anti-CD20 antibodies is to be assumed; the risk is presumed to exist under ublituximab as well. Enteroviral encephalitis generally manifests as self-limiting condition in immunocompetent individuals. In patients with compromised immune systems, these conditions can present clinically in a variety of ways. Psychiatric abnormalities are often the first symptom to appear, and epileptic seizures may also occur. However, there is encouraging evidence of a positive therapeutic response to intravenous immunoglobulins and various antiviral drugs (e.g. pleconaril, favipiravir, pocapavir, ribavirin).

In summary, in light of the latest reports, enterovirus-associated infections in patients receiving anti-CD20 antibodies are thought to be less a matter of substance-specific risks and more a matter of a class effect. In instances of new-onset symptoms, the differential diagnosis should always include consideration of enterovirus encephalitis.