Early Treatment Intervention in MS—Delaying Development of Subsequent Disease
abstracts & commentary
Sources: Jacobs LD, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000;343:898-904; Scott TF, et al. Short-term prognosis in early relapsing-remitting multiple sclerosis. Neurology 2000;55:689-693; Noseworthy JH, et al. Medical progress: Multiple sclerosis. N Engl J Med 2000;343: 938-104.
In a controlled trial organized by jacobs and Beck, 383 patients with a first acute demyelinating event (optic neuritis, transverse myeltis, or a brainstem syndrome), and two or more clinically silent lesions on brain MRI, were treated with IV methylprednisolone, and then randomized to receive either an interferon beta-1a injection (30 mcg IM q week) or a placebo. Patients were followed over three years, monitoring for the development of "clinically definite" multiple sclerosis (CDMS), with a second attack and/or change in neurologic disability. The cumulative probability of progression to CDMS was 35% in the interferon beta-1a group and 50% in the placebo group (rate ratio 0.56, P = 0.002). In other words, there was a 44% lower cumulative probability of converting to CDMS in the interferon beta-1a treated group. There was also a highly significant reduction in the volume of lesions on T2-weighted brain MRI scans, as well as fewer new and enhancing lesions, in patients receiving interferon beta-1a. Clinical and MRI benefits were seen within six months of treatment.
Scott and colleagues prospectively studied 98 newly diagnosed MS patients over an average follow-up of 37 months. Six prognostic factors were recorded: age at onset, symptoms at onset, MRI status, interval between first and second attack, attack frequency in the first two years, and completeness of recovery from initial attacks. Using these parameters, 24% of their patients had a high risk of progression (4-6 risk factors) and, in fact, went on to develop higher disability (EDSS > 3.5) within the short study period.
Noseworthy and associates provide a comprehensive review article on MS, including pathogenesis, epidemiologic features, diagnosis and clinical course, genetic factors, and treatment of relapsing and progressive forms of disease.
Commentary
Studies on the natural history of MS have revealed that the majority of patients will have significant disability and evolve to a secondary progressive course. Recent insights into early MS brain pathology as revealed by novel MRI methodology (e.g., whole brain spectroscopy, magnetization transfer imaging, brain atrophy measures) also define an early and relentless disease process that is often subclinical. Other subtle global brain dysfunction with early cognitive impairment is difficult for the clinician to measure in the average office setting. Given this body of information, a label of "benign" MS applied to a patient at diagnosis is probably falsely reassuring, to both the patient and clinician.
Jacobs and colleagues selected a group of patients with their first demyelinating event who, on the basis of their MRI scans (³ 2 lesions), were more likely than not to go on to CDMS. This early disease intervention study confirmed the ability of interferon beta-1a to forestall subsequent attacks and stabilize disease activity on brain MRI. This study bolsters the recommendation of the National MS Society that clinicians consider initiating therapy after a definite diagnosis of relapsing-remitting MS. However, one could argue to start immediately at the "first" attack, especially in patients with poor prognostic factors. —Brian R. Apatoff
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