Early Intensive DMT Use May Prevent Greater Long-term Disability in RRMS

Early intensive treatment was more efficacious at slowing disease accumulation in patients with relapsing-remitting multiple sclerosis (RRMS) vs initiating therapy with a moderate-efficacy disease-modifying treatment (DMT) prior to switching to a higher-efficacy DMT.

Early intensive treatment (EIT) for relapsing-remitting multiple sclerosis (RRMS) proved to be more efficacious at slowing disease accumulation compared with initiating therapy with a moderate-efficacy disease-modifying treatment (DMT) before escalating to a higher-efficacy DMT, according to study findings published in Therapeutic Advances in Neurological Disorders. 

“The most important goal of MS therapy is prevention of long-term disability accumulation,” the authors wrote. “But no consensus exists on how aggressively to treat RRMS nor on the timing of the treatment.”

The Italian MS Register provided the multicenter, observational, retrospective cohort study data on 726 patients with RRMS who were included in the final analysis because they had at least 5 years of follow-up, a first visit within the 3 years after disease onset, and at least 3 Expanded Disability Status Scale (EDSS) score evaluations—all after DMT initiation. These cohorts consisted of the EIT group (n = 363), whose first DMT was fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, or cladribine, and the escalation to higher-efficacy DMT group (ESC; n = 363), whose first DMT was glatiramer acetate (GA), interferon (IFN) beta, azathioprine, teriflunomide, or dimethylfumarate treatment before switching to the higher-efficacy agent after at least 1 year and because of lack of efficacy.

With their cohort followed for a median (interquartile range [IQR]) of 8.5 (6.5-11.7) years, the overall results show that the mean delta-EDSS differences increased at 3 important time points:

  • 1 year: 0.1 (95% CI, 0.01-0.19; P = .03)
  • 5 years: 0.30 (95% CI, 0.07-0.53; P = .009)
  • 10 years: 0.67 (95% CI, 0.31-1.03; P = .0003)

In fact, the authors pointed out, “the mean annual delta-EDSS values were all significantly (P < .02) higher in the ESC group compared with the EIT group.”

Analyses also found:

  • EIT patients were older at first DMT (mean [SD] age, 31.13 [10.06] years) compared with the ESC patients (mean [SD] age, 29.37 [9.22] years).
  • EIT patients had a shorter disease duration at first DMT (12.69 [9.61] months) vs the ESC patients (14.04 [9.64] months).
  • EIT patients were more disabled at first DMT (EDSS score, 2.63 [1.60]) vs the ESC patients (EDSS score, 1.85 [1.26]).
  • EIT patients had fewer EDSS evaluations at their first follow-up (21.99 [15.71]) vs the ESC patients (24.43 [16.75]).

Patients in the ESC group most often started their DMT therapy with IFB beta 1a subcutaneous (44.63%), followed by IFN beta 1a intramuscular (19.83%), IFN beta 1b subcutaneous (19.56%), GA (9.09%), and azathioprine (6.89%). After a median (IQR) of 6.3 (3.1-8.4) years, they usually escalated to natalizumab (42.98%), fingolimod (38.84%), mitoxantrone (14.05%), ocrelizumab (2.20%), alemtuzumab (n = 6, 1.65%), or cladribine (0.28%).

In contrast, patients in the EIT group most often had as their first DMT, natalizumab (40.77%), followed by mitoxantrone (38.84%), fingolimod (17.63%), and cladribine (2.75%). None received alemtuzumab or ocrelizumab. Their median (IQR) exposure was 7.2 (5.3-10.3) years.

At baseline, EDSS scores were close to equal (ESC cohort, 2.63 [1.54]; EIT cohort, 2.61 [1.57]), but EIT patients were slightly older (31.04 [10.02] vs 30.28 [9.26] years) and more of them had a disease relapse in the 2 years before DMT initiation (313 [86.23%] vs 308 [84.85%]).

Overall, from baseline to year 10 (the final year of follow-up), despite estimated EDSS scores increasing in both groups—from a mean 2.45 (95% CI, 2.26-2.64) at baseline to 3.07 (95% CI 2.81-3.33) in the EIT group and 2.52 (95% CI, 2.33-2.71) to 3.81 (95% CI, 3.58-4.04) in the ESC group—the authors highlighted how “in our study, the EIT algorithm was strongly associated with lower disability progression, expressed by the increase of the 12-month EDSS score, and this effect not only persisted, but continued to increase over time.”

“These findings may drive the treatment decisions of physicians, in particular in the cases of naïve patients with poor prognosis factors at the onset of disease,” the concluded.

Still, further studies are necessary, they emphasized, in light of long-term safety concerns regarding severe adverse events connected to the higher-efficacy DMTs.


Iaffaldano P, Lucisano G, Caputo F, et al; Italian MS Register. Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies. Ther Adv Neurol Disord. Published online May 31, 2021. doi:10.1177/1756286421101957