Oral MS treatments breakthrough

Three large randomised trials have provided strong evidence that new oral treatments for relapsing-remitting multiple sclerosis (MS) offer an advance on interferon beta-1a, with the prospect of transforming treatment if long-term studies provide evidence of safety (NEJM 2010; 362:387–401; 402–15; 416–26).

Novartis’s sphingosine-1-phosphate receptor modulator fingolimod, 0.5 or 1.25mg/day, significantly reduced annualised relapse rate (0.18 and 0.16 versus 0.40 with placebo), and reduced disease progression over two years (hazard ratio 0.70 and 0.68). Cumulative probability of worsening disability was 18, 17 and 24%, respectively.

In a second trial, fingolimod 0.5 or 1.25mg/day was associated with lower annualised relapse rates (0.16 and 0.20 versus 0.33 with interferon beta-1a 30mg weekly), but there was no difference in disability progression over one year. Fingolimod 1.25mg/day was associated with two fatal infections (disseminated primary varicella zoster and herpes simplex encephalitis).

In both trials the clinical findings were supported by differences in MRI-related measures. Adverse effects associated with fingolimod included nonfatal herpes virus infections, bradycardia and atrioventricular block, hypertension, macular oedema, skin cancer and raised liver enzymes.

Merck Serono’s immunomodulator cladribine 3.5 or 5.25mg/kg/day significantly reduced annualised relapse rate (0.14 and 0.15 versus 0.33 with placebo) and reduced by about one-third the risk of three-month sustained progression of disability. Again, the findings were consistent with a reduction in brain lesions by MRI. Lymphocytopenia occurred in 22 and 32% of patients taking cladribine and 2% with placebo; other adverse effects associated with cladribine included herpes zoster.