Are Corticosteroids Efficacious for Preventing or Treating Neutralizing Antibodies in Multiple Sclerosis Patients Treated With Beta-Interferons?

Abstract

Persistent, high-titer neutralizing antibodies (NAbs) reduce or eliminate the biologic activity of interferon-beta (IFNB) therapies for multiple sclerosis (MS) and are associated with reduction in efficacy. Most patients who develop NAbs have preceding detectable binding antibodies. There is no consensus on prevention or management of NAb-positive patients but switching to noninterferon therapy and use of immunosuppressive strategies, especially corticosteroids, has been proposed. To evaluate the evidence supporting the efficacy of corticosteroid therapy for (a) reducing the incidence of NAbs; and (b) improving markers of interferon bioavailability, reducing NAbs titers, and improving clinical outcomes in NAb-positive patients with MS receiving IFNB therapy. The objective was addressed through the development of a structured critically appraised topic. This included a case scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of neuroimmunology and multiple sclerosis. We selected 4 papers for detailed review, all of which used pulsed methylprednisolone therapy, either alone or in combination with another immunosuppressive therapy. A randomized open-label trial showed that monthly intravenous methylprednisolone initiated at INFB therapy onset was associated with a lower risk of an ever-positive NAb result but was insufficiently sensitive to detect an effect on more clinically meaningful high-titer NAbs. A randomized controlled trial for patients with active disease despite IFNB therapy showed that baseline NAb titers were reduced by subsequent intravenous methylprednisolone treatment, but the incidence of NAbs was too small to assess clinical relevance. Small open-label observational studies suggest that pulse methylprednisolone, alone or in combination with azathioprine, does not restore the bioavailability of IFNB. Pulse methylprednisolone therapy may reduce the risk of developing NAbs (but possibly not high-titer NAbs of clinical importance) when coadministered with newly initiated IFNB therapy. However, current evidence suggests that methylprednisolone therapy does not restore IFNB biologic response in established NAB-positive MS patients.