Interferon β‐1a for early multiple sclerosis: CHAMPS trial subgroup analyses

Abstract

The objective of this work was to assess the effect of interferon beta-1a (Avonex) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30 microg interferon beta-1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem-cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndromes.

Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI

“…We found a 23.8% 5 year risk of developing MS, a value in accordance with previous reports, which estimate MS conversion rates between 10% and 30% in these patients [3][4][5][6][7][8][9]. The Optic Neuritis Treatment Trial [3], the largest study on MS risk after ON, included 191 patients with ON without baseline brain MRI lesions, with a conversion risk in this subgroup of 16% at 5 years, 22% at 10 years and 25% at 15 years, suggesting higher risk of MS development in the first 5 years and very low probability of conversion after 10 years of follow-up.…”

“…Therefore, when assessing and managing a patient with isolated ON without an identifiable etiology, the possibility of future development of MS has to be considered. Determining which patients have a higher risk of conversion to MS is important, as studies suggest that there may be a benefit from early immunomodulatory treatment in patients with clinically isolated syndrome (CIS), including ON [4][5][6][7][8][9][10]. Although the presence of one or more lesions on baseline brain MRI has been identified as the strongest predictor of MS conversion [3,[11][12][13][14][15][16], there are patients with normal baseline MRI who also develop MS and predictors of conversion are still to be determined in this subgroup of patients.…”

Interferon Beta and Glatiramer Acetate Therapy

“…Inclusion criteria selected for patients with active clinical and MRI disease. Subgroup analyses demonstrated more pronounced effects in those with more disease activity [30]. Regression to the mean, an issue that continues to plague more recent MS trials, posits that variables that are extreme on the first measurement will tend to be close to the average on the second measurement.…”

Acute inflammatory myelopathies

“…That spinal cord CIS patients with abnormal brain studies are at high risk for experiencing a second clinical attack was confirmed in a subgroup analysis of the CHAMPS clinical trial, a randomized, blinded, placebo-controlled study of the impact of once-weekly interferon b-1a on the risk of conversion from an initial demyelinating event to CDMS (Beck et al, 2002). Eighty-three enrolled patients presented with spinal cord CIS and had two or more brain lesions typical of MS. Forty-one received interferon b-1a and 42 received placebo.…”

“…In recent clinical trials of patients presenting with a clinically isolated syndrome (CIS) who also had abnormalities on brain MRI consistent with MS, spinal cord presentations constituted 19-22% of cases (Beck et al, 2002;Polman et al, 2008). These and other studies showed that disease-modifying therapies used for the treatment of MS were effective in delaying the time to a second clinical attack in patients who presented with CIS and who had brain MRI scans suggestive of MS (Filippi et al, 2004;Comi et al, 2009).…”