The clinical course of multiple sclerosis (MS) is highly variable among patients, thus creating important challenges for the neurologist to appropriately treat and monitor patient progress. Despite some patients having apparently similar symptom severity at MS disease onset, their prognoses may differ greatly. To this end, we believe that a proactive disposition on the part of the neurologist to identify prognostic "red flags" early in the disease course can lead to much better long-term outcomes for the patient in terms of reduced disability and improved quality of life. Here, we present a prognosis tool in the form of a checklist of clinical, imaging and biomarker parameters which, based on consensus in the literature and on our own clinical experiences, we have established to be associated with poorer or improved clinical outcomes. The neurologist is encouraged to use this tool to identify the presence or absence of specific variables in individual patients at disease onset and thereby implement sufficiently effective treatment strategies that appropriately address the likely prognosis for each patient.

• Keywords
• biomarkers, clinical parameters, evoked potentials, magnetic resonance imaging (MRI), multiple sclerosis, optical coherence tomography, prognosis, treatment,
• MeSH
• Biomarkers MeSH
• Quality of Life MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Prognosis MeSH
• Recurrence MeSH
• Multiple Sclerosis * diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH

Objective: To identify predictors of clinical disease activity after treatment change to higher-dose interferon beta-1a in relapsing-remitting multiple sclerosis (MS). Methods: This was a retrospective-prospective observational multicenter study. We enrolled patients with at least one relapse on platform injectable therapy who were changed to 44 μg interferon beta-1a. Our primary endpoint was the clinical disease activity-free (cDAF) status at 6, 12, 18, and 24 months. Secondary endponts included relapse-free status and disability progression-free status at different timepoints. The primary predictor of interest was the monosymptomatic vs. polysymptomatic index relapse, based on the number of affected functional systems from the Kurtzke scale during the last relapse prior to baseline. Other secondary predictors of clinical disease activity were analyzed based on different demographic and relapse characteristics. Kaplan-Meier estimates of the cumulative probability of remaining in cDAF status were performed. The time to clinical disease activity was compared between groups using univariate Kaplan-Meier analysis and multivariate Cox regression. Multivariate analyses were processed in the form of CART (Classification & Regression Trees). Results: A total of 300 patients entered the study; 233 (77.7%) of them completed the 24-month study period and 67 patients (22.3%) terminated early. The proportion of patients in cDAF status was 84.7, 69.5, 57.5, and 54.2% at 6, 12, 18, and 24 months. After 2 years of follow-up, 55.9% of patients remained relapse-free and 87.8% of patients remained disability progression-free. At all timepoints, the polysymptomatic index relapse was the most significant predictor of clinical disease activity of all studied variables. Hazard ratio of cDAF status for patients with monosymptomatic vs. polysymptomatic index relapse was 1.94 (95% CI 1.38-2.73). CART analyses also confirmed the polysymptomatic index relapse being the strongest predictor of clinical disease activity, followed by higher number of pre-baseline relapses with the most significant effect in the monosymptomatic index relapse group. The next strongest predictors of clinical disease activity were cerebellar syndrome as the most disabled Kurtzke functional system for the monosymptomatic relapse group, and age at first MS symptom ≥ 45 for the polysymptomatic relapse group. Conclusions: Patients with a polysymptomatic index relapse and/or higher number of relapses within 2 years prior to baseline are at high risk of clinical disease activity, despite treatment change to higher-dose interferon beta-1a from other platform injectable therapy. Trial registration: State Institute of Drug Control (SUKL), URL: http://www.sukl.eu/modules/nps/index.php?h=study&a=detail&id=958&lang=2, registration number 1205090000.

• Keywords
• disease activity, interferon beta, multiple sclerosis, progression, relapse,
• Publication type
• Journal Article MeSH