NATIONAL HARBOR, MD—Long-term follow-up from the BENEFIT trial, in which patients with clinically isolated syndrome (CIS) were treated with interferon beta-1b, confirmed the relationship between MRI metrics and clinical outcomes after 11 years of treatment, according to data presented at the 2016 CMSC Annual Meeting. Results also indicated that patients with more active disease tended to have smaller cervical spinal cord volumes and that cognition (as measured by mental processing speed) was related to number of lesions.
Patients with CIS who had early treatment with interferon beta-1b in the BENEFIT trial maintained an overall favorable disease course, with some clinical differences that favored treatment start at CIS, including lower annualized relapse rate (ARR), higher Paced Auditory Serial Addition Task (PASAT) score, and longer time to clinically definite multiple sclerosis (MS). “The 11-year follow-up of this trial provides an opportunity to assess the relationship between long-term clinical outcomes and structural assessments by MRI and optical coherence tomography (OCT),” said Edward J. Fox, MD, PhD, a neurologist at Central Texas Neurology Consultants in Round Rock, Texas, and colleagues.
Edward J. Fox, MD, PhD
The objective of the present study was to assess correlations between clinical, MRI, and OCT outcomes over 11 years. In the original BENEFIT trial, patients with CIS who had two or more silent brain lesions were randomized to 250 µg of interferon beta-1b (ie, early treatment) or placebo (ie, delayed treatment) subcutaneously every other day. Patients remained on placebo until conversion to clinically definite MS or for two years, whichever came first. Eleven years after initial randomization, all patients were approached to undergo cross-sectional follow-up that included clinical, MRI, and OCT assessment.
Clinical parameters included ARR, Expanded Disability Status Score (EDSS), Kurtzke Functional Status Scale (KFSS), MS Functional Composite (MSFC), PASAT score, and Symbol-Digit Modality Test (SDMT). Correlation was also assessed between mental processing speed (the sum of the z scores for PASAT and SDMT adjusted for education status, age, and sex) and selected MRI parameters.
Of the 468 patients originally randomized, 278 (71.3%) participated in the BENEFIT 11 follow-up study. This population included 167 patients in the original early-treatment group (57.2% of the original cohort) and 111 patients from the original delayed-treatment group (63.1% of the original cohort).
Year 11 MRI and OCT assessments were conducted in 191 patients (68.7%) and 86 patients (30.9%, two patients missing data), respectively. Little difference between the early- and delayed-treatments groups, with respect to MRI and OCT findings, was noted, with the exception of a difference in median number of T1-hypointense lesions. The early-treatment group had 4.0 lesions, and the delayed-treatment group had 2.0 lesions.
Regarding MRI, significant positive correlations in the overall BENEFIT 11 population were observed between ARR and volume of T1 lesions (r = 0.212), ARR and volume of T2 lesions (r = 0.216), EDSS score and T1 hypointensity volume (r = 0.281), and EDSS and T2 volume (r = 0.244). Significant negative correlations in the overall BENEFIT 11 population were observed between ARR and mean upper cervical cord area (MUCCA) (r = –0.208), EDSS and MUCCA (r = –0.194), and MSFC and T1 lesion volume (r = –0.183) and T2 lesion volume (r = –0.213). Mental processing speed correlated negatively with number of T1 lesions (r = –0.176).
Regarding OCT, significant positive correlations in the BENEFIT 11 population were observed between PASAT and minimum global retinal nerve fiber layer thickness (r = 0.271). Significant negative correlations were observed between ARR and global retinal nerve fiber layer thickness (r = –0.233) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.239), T1 lesion volume and minimum global retinal nerve fiber layer thickness (r = 0.255) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.340), and T2 lesion volume and global retinal nerve fiber layer thickness (r = 0.307) and papillomacular bundle-retinal nerve fiber layer thickness (r = –0.392). No significant correlations were found between OCT parameters and EDSS, KFSS, MSFC, SDMT, normalized brain volume, mean cortical thickness, normalized thalamic volume, or visual acuity.
“Results from BENEFIT 11 confirmed the relationship between MRI measures of disease and long-term outcomes,” said Dr. Fox and colleagues. “Significant correlations of lesion volume with EDSS, ARR, and MSFC, as well as with minimum global retinal nerve fiber layer thickness and papillomacular bundle-retinal nerve fiber layer thickness were found, while MUCCA significantly correlated with EDSS and ARR.” These findings, the researchers said, highlight the importance of monitoring MRI activity for assessing disease status.
This study was supported by Bayer HealthCare Pharmaceuticals.
—Glenn S. Williams