Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management

Abstract

Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.

Keywords: immunosuppression; multiple sclerosis; opportunistic infections.

Figure 1.

Updated progressive multifocal leukoencephalopathy (PML) risk estimate based on natalizumab exposure, previous immunosuppressant use, and anti–JC virus (JCV) antibody index. Reprinted with permission from Elsevier from Lancet Neurology: Ho PR, Koendgen H, Campbell N, Haddock B, Richman S, Chang I. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol 2017; 16(11):925–933. Conditional probability of developing PML using the life table method in each year of treatment is presented, with multiple imputation used to account for missing data in the pooled cohort (n = 21 696). PML risk estimates were calculated using a life table method in the pooled cohort of anti-JCV antibody-positive patients who participated in the STRATIFY-2 [41], TOP [42], TYGRIS [43], and STRATA [44] clinical studies. ^aData beyond 6 years of treatment are scarce. ^bAlthough estimates below 0.1 per 1000 patients were rounded up to 0.1 per 1000 patients for regulatory documents and management guidelines, these estimates are shown with greater precision in this article. ^cVariability might be due to small sample size. Abbreviation: CI, confidence interval.