Researchers identify clinical and MRI biomarkers that may help predict outcomes in patients with relapsing-remitting MS up to eight years after starting therapy.
HONOLULU—Higher brain volume at baseline and a greater medication possession ratio predicted improved long-term clinical outcomes among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 63rd Annual Meeting of the American Academy of Neurology. In addition, a higher baseline Expanded Disability Status Scale (EDSS) score and a greater early increase in EDSS score predicted worse outcomes, researchers reported.
“Given the heterogeneous nature of MS, it is important to identify prognostic factors that may predict outcomes as long as eight years after starting therapy,” stated Anthony Traboulsee, MD, Assistant Professor of Neurology at the University of British Columbia in Vancouver, and colleagues. “Assessing baseline brain volume and closely monitoring early disability status may be important to consider in monitoring and treatment decisions.”
Long-Term Follow-Up After Treatment Initiation
Dr. Traboulsee’s group conducted the Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) long-term follow-up (LTFU) study to analyze early clinical and MRI variables as predictors of long-term outcomes in patients with relapsing-remitting MS. The PRISMS LTFU cohort was followed prospectively for as long as eight years, with a 68% patient return rate in the follow-up. “Assessment protocols remained consistent through the course of the PRISMS study, thereby providing one of the most complete datasets of its type available,” noted the investigators.
A total of 382 patients were included in the LTFU follow-up to PRISMS, in which 560 patients were originally randomized. Among the 382 patients in the LTFU, 136 patients had been initially randomized to receive interferon beta-1a 44 µg; 123 patients had received interferon beta-1a 22 µg subcutaneously three times per week; and 123 participants had received placebo. Post-hoc exploratory analyses were conducted on data collected from all LTFU patients and in the subcohort originally randomized to receive subcutaneous interferon beta-1a, who were referred to as early-start patients (n = 259).
Baseline variables and medication possession ratio, as an indicator of subcutaneous interferon beta-1a treatment exposure, were explored as candidate prognostic factors for outcomes measured from baseline to LTFU (for up to eight years). The authors also investigated indicators of early clinical and MRI activity from baseline to month 24 as candidate prognostic factors for outcomes measured from month 24 to LTFU.
Predicting Favorable and Unfavorable Outcomes in MS
The researchers found that age, duration of MS, baseline EDSS score, baseline log (T2 disease of burden), and baseline brain volume were univariate predictors for nearly all long-term outcomes as measured from baseline to LTFU among all patients and early-start patients. Medication possession ratio predicted most of the long-term outcomes measured from baseline to LTFU in all patients and was a predictor for several outcomes in early-start patients.
Early change in EDSS score up to two years was a univariate predictor for virtually all outcomes measured from month 24 to LTFU in all patients and early-start patients, according to the investigators. In addition, EDSS progression and the number of EDSS progressions during the first 24 months were frequent predictors for clinical outcomes as measured from month 24 to LTFU in all patients and early-start patients.
“The early MRI activity indicators were significant univariate predictors of several long-term disability outcomes, but not as frequently as seen with early EDSS progression,” reported Dr. Traboulsee and colleagues. “Brain volumes at baseline continued to be a predictor in all final multivariate models for all long-term clinical outcomes in both patient groups measured from baseline to LTFU. EDSS score at baseline continued to be a predictor in most multivariate models in both patient groups measured from baseline to LTFU.”
In several multivariate models, medication possession ratio continued to be a predictor for all long-term clinical outcomes in the all-patient cohort measured from baseline to LTFU, noted the investigators. The change in EDSS score from baseline to month 24 continued to be a predictor in nearly all final multivariate models for long-term clinical outcomes in all patients, and in all final multivariate models for all long-term clinical outcomes in early-start patients. Also, short-term MRI activity was predictive of some of the long-term clinical outcomes.
“These data suggest that a good early clinical response—no EDSS progression—can be predictive of a favorable long-term outcome,” Dr. Traboulsee and colleagues concluded. “However, patients who show worrisome signs of early disease progression may require earlier therapeutic review."