Age at onset, exposure to disease-modifying drugs (DMDs), disability at onset, MRI criteria, and oligoclonal bands affect the likelihood of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS), according to research published in the September issue of Multiple Sclerosis Journal. The study results corroborate and augment previous research into factors that predict clinical conversion, said the authors.
In addition, the researchers developed and validated a nomogram intended to predict individualized risk of relapse after CIS. The nomogram’s estimated probabilities of conversion to MS had high concordance with observed rates of conversion.
An Analysis of Prospective Data
Tim Spelman, MBBS, PhD, Head of Statistics at the Melbourne Brain Center at the Royal Melbourne Hospital, and colleagues examined data for 3,296 patients with CIS who were enrolled in the prospective MSBase Incident Study, a substudy of the MSBase Registry. Participants presented to 50 clinics in 22 countries. At each visit, investigators recorded participants’ Expanded Disability Status Scale (EDSS) score, date of relapse onset, and dates of DMD initiation and discontinuation. The primary outcome was the time to first relapse following CIS. The researchers defined clinically definite MS according to the Poser criteria. Patients were followed up until first relapse after CIS or last recorded clinic visit.
Dr. Spelman and colleagues used Cox proportional hazards regression to examine the correlation between previously identified predictors and time to first relapse after CIS. They used their baseline-adjusted data modeling to create a nomogram to predict conversion to clinically definite MS.
Drug Exposure Reduced Risk
Approximately 43% of participants initiated intramuscular interferon β-1a, 34% initiated subcutaneous interferon β-1a, 18% initiated interferon β-1b, and 14% initiated glatiramer acetate. In all, 1,953 patients (59%) had a relapse during a median follow-up of 1.92 years.
Older age at CIS was associated with a 10% reduction in the risk of clinical conversion. Every one-point increase in baseline EDSS score was associated with 1.16 times the rate of subsequent conversion. Compared with the optic pathway, first symptom location in the brainstem was associated with 1.17 times the rate of second attack, and first symptom location in the supratentorial region was associated with 1.29 times the rate of second attack. Any exposure to DMD during follow-up was associated with a 42% rate reduction in time to first relapse, compared with nonexposure.
CSF-restricted oligoclonal bands were associated with 1.52 times the rate of relapse, compared with the absence of oligoclonal bands. Having at least one T1 gadolinium-enhancing lesion was associated with 1.24 times the rate of relapse. Having three or more periventricular lesions was associated with 1.68 times the rate of relapse, compared with no lesions. Having at least one infratentorial and at least one juxtacortical lesion on brain MRI were associated with 1.21 times and 1.21 times the rate of first post-CIS relapse, respectively, compared with no lesions.
“This multinational, prospective study represents the largest post-CIS cohort reported to date,” said Dr. Spelman. “Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD treatment intervention, [thus] facilitating more favorable patient outcomes.”
—Erik Greb
Suggested Reading
Spelman T, Meyniel C, Rojas JI, et al. Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice. Mult Scler. 2017;23(10):1346-1357.