In patients treated with natalizumab, PML incidence was about 11 cases per 1000 patients with 25 to 48 months of treatment, prior immunosuppressant use, and anti–JC virus antibody–positive status. The incidence was estimated to be 0.09 cases or fewer per 1000 antibody-negative patients.

In this placebo-controlled, phase 3 trial involving patients with relapsing–remitting multiple sclerosis, oral laquinimod administered once daily reduced the number of clinical relapses and slowed disability progression.

Analysis of tissue from brain cortex obtained during biopsy of white-matter lesions in persons with early-stage multiple sclerosis suggests that cortical demyelinating lesions are common and inflammatory.

In this trial, teriflunomide reduced annualized relapse rates and disability progression over 108 weeks of treatment in patients with relapsing MS, although diarrhea, nausea, hair thinning, and abnormalities in alanine aminotransferase levels were reported.

In this 12-month trial involving patients with relapsing–remitting multiple sclerosis, oral fingolimod was more effective than intramuscular interferon beta-1a in reducing relapse rates. Adverse events associated with fingolimod included herpesvirus infections (two fatal infections), atrioventricular block, macular edema, skin cancer, and liver-enzyme elevation.

In this 96-week, placebo-controlled trial, oral cladribine reduced relapse rates and lowered the risk of sustained disability in patients with relapsing–remitting multiple sclerosis. Patients who were treated with cladribine had large reductions in lymphocyte counts and more infections, including herpes zoster and one death from reactivation of tuberculosis.

In this 24-month, randomized trial involving patients with relapsing–remitting multiple sclerosis, oral fingolimod reduced the rates of relapse and disability progression, as compared with placebo. Adverse events reported in patients treated with fingolimod included bradycardia, atrioventricular conduction block, macular edema, elevations in liver-enzyme levels, and mild hypertension.

Progressive multifocal leukoencephalopathy (PML) is a rare complication of natalizumab treatment and is caused by the JC virus. In this study of 19 patients with multiple sclerosis who had no symptoms of PML, the prevalence of JC virus in blood and urine increased after treatment with natalizumab. JC virus regulatory-region sequences were similar to those usually found in PML.

This report describes progressive multifocal leukoencephalopathy in a patient who was receiving natalizumab therapy for multiple sclerosis. Plasma exchange was used to accelerate the clearance of natalizumab. Three weeks after plasma exchange, the patient's condition worsened neurologically because of the development of an immune-reconstitution inflammatory syndrome, but his condition improved after several weeks.

This report describes a 52-year-old patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy developed after 12 months of natalizumab therapy. He was treated with plasma exchange and immunoadsorption to eliminate natalizumab. After initial clinical improvement, immune-reconstitution inflammatory syndrome developed and the patient deteriorated clinically, but he survived and improved neurologically.

In this randomized, phase 2 trial involving previously untreated patients with early, relapsing–remitting multiple sclerosis, alemtuzumab, a monoclonal antibody targeting CD52 on lymphocytes and monocytes, was more effective than interferon beta-1a in reducing the progression of disability and relapse. Alemtuzumab caused autoimmune complications, including immune thrombocytopenic purpura (resulting in one death) and thyroid disorders.