A higher frequency of early relapses, as well as a larger volume of lesions and older age at disease onset, increase the risk of transitioning from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS), according to a study.
The study, “Early cortical pathology and early relapses predict the risk of developing secondary progressive MS,” was recently presented at the 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place through Friday in Berlin.
Antonio Scalfari, MD, PhD, from Imperial College London in the United Kingdom, presented the data.
In patients with RRMS, a high frequency of early relapses correlates with a greater risk of developing severe disability, which suggests that biological mechanisms occurring early in disease course affect long-term disease progression.
Aiming to study if early disease processes in the cerebral cortex — a gray matter area of the brain implicated in diverse functions, including motor control, memory, and information processing — and early relapses are associated with a greater risk of transitioning from RRMS to SPMS, a team from the U.K. and Italy used magnetic resonance imaging (MRI) methods to analyze the number of cortical (CLs) and white matter (WM) lesions, as well as cortical thinning in 219 RRMS patients. White matter is made of nerve fibers and is the main target for immune attacks in MS.
Of these patients, 116 had one relapse, 53 had two relapses and 50 had three or more relapses during the first two years. These patients were followed for a mean of 7.9 years.
Results showed that 59 patients (27%) converted to SPMS over a mean period of 6.1 years.
At disease onset, a total of 674 CLs in 166 patients (76%) were found. A higher number of CLs correlated with a greater risk of SPMS transition — patients with seven or more lesions transitioned to SPMS more quickly than those with fewer lesions.
Patients with more CLs also had a faster rate of global cortical thinning, with yearly rates of 0.93% for those with no lesions, 0.99% for those with one to three lesions, 1.13% for those with four to six lesions, and 1.33% for those with seven or more.
Among the 53 patients with no CLs, none transitioned to SPMS, and only four reached a score of 4 on the Expanded Disability Status Scale, which corresponds to significant disability, but still maintaining self-sufficiency and the ability to walk without aid or rest for 500 meters.
Compared with patients with a low (one relapse) or mid (two relapses) frequency of early relapses, those with a high frequency of relapses (three or more) had a larger volume of WM lesions and CLs at disease onset — mean 544 mm3 (high group), 386.8 mm3 (mid group), and 181.6 mm3 (low group).
MS patients with high relapse frequency also had an increased accumulation of CLs — mean 790.5 mm3, compared with 138.8 in the mid group and 118.8 mm3 in the low group; experienced a greater yearly rate of cortical shrinking over time (mean loss of 0.94, 0.79 and 0.47%, respectively); and transitioned to SPMS more rapidly (mean time of 7.4 years, compared with 10 years in the mid group and 9.3 years in the low relapse group).
The data also showed that older age at onset, larger baseline CL and WM lesion volume, early cortical thinning, and three or more early relapses were independent predictors of a higher risk of transition to SPMS.
These results show that “severe focal cortical damage at onset distinguishes patients destined to have frequent early relapses and a rapid conversion to SPMS, which is driven by the worsening global cortical pathology over time,” Scalfari said in his presentation.
According to him, processes leading to SPMS transition “are associated to the development of the cortical pathology and already active during the early disease stage, suggesting an early window of therapeutic opportunity for achieving a better disease control.”
Based on the results, the team suggested that “age, the extent of cortical damage at onset, and the frequency of early relapses can be used for patients’ stratification aimed at therapeutic optimization,” Scalfari concluded.
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