Early Intensive MS Treatment Yields Better Outcomes Than Escalation Approach

Pietro Iaffaldano, MD

Data presented in a platform session at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, suggest that early intensive treatment in patients with relapsing multiple sclerosis (MS) is more effective at controlling disability progression, with an increasing effect over time, compared with an escalation therapy approach.¹

Notably, this increasing effect was observed even in light of patients utilizing an escalation approach when switching to higher-efficacy disease-modifying therapy (DMT).

The data were presented by Pietro Iaffaldano, MD, assistant professor of neurology, University of Bari Aldo Moro, who, along with his colleagues, hinted at the importance of these findings due to the fact that “no consensus exists on how to aggressively and timely treat relapsing-remitting multiple sclerosis patients.”

The total study cohort consisted of 2652 patients with relapsing MS from 62 Italian MS centers, with a 1:1 propensity score-matched cohort of 365 pairs. The median follow-up after the initiation of first DMT was 8.5 years (interquartile range [IQR], 6.5–11.7). Those in the escalation group continued to a higher-efficacy DMT after a median time of 5.1 years (3.1–8.4).

Disability trajectories were evaluated by applying a longitudinal model for repeated measures with an autoregressive variance-covariance structure, and the effect of early versus late start of high-efficacy DMT was evaluated via mean annual Expanded Disability Status Scale (EDSS) score changes compared to baseline values in both groups.

READ MORE: Fatigue Plays A Factor in Multiple Sclerosis Daily Functioning​

The early intensive group included individuals who received either fingolimod (Gilenya; Novartis), natalizumab (Tysabri; Biogen), mitoxantrone (Novantrone; EMD Serono), alemtuzumab (Lemtrada; Sanofi), ocrelizumab (Ocrevus; Genentech), or cladribine (Mavenclad; EMD Serono) as first DMT. The escalation group consisted of those individuals who received a high efficacy DMT after ≥1 year of glatiramer acetate, interferon, azathioprine, teriflunomide, or dimethyl fumarate treatment.

Baseline EDSS values were estimated as 2.52 (95% CI, 2.33–2.71) in the escalation group compared to 2.45 (95% CI, 2.26–2.64) in the early intensive group.

Iaffaldano and colleagues observed that mean delta-EDSS score at each 12-month period was significantly higher in the escalation group compared to the early intensive group (P <.02). Particularly, the mean delta-EDSS differences between the 2 groups tended to increase from 0.1 (95% CI, 0.01–0.19; P = .03) at 1 year to 0.30 (95% CI, 0.07–0.53; P = .009) at 5 years, and to 0.67 (95% CI, 0.31–1.03; P = .0003) at the 10-year mark.

These data are not the first to explore the differences in treatment approach for MS, as the conversation around induction versus escalation therapy has been ongoing. In 2019, data from a cohort study of 592 patients with MS suggested that real-world escalation approaches may be inadequate to prevent unfavorable long-term outcomes.²

That trial, conducted by Katharine Harding, PhD, of the Institute of Psychological Medicine and Clinical Neuroscience at the School of Medicine at Cardiff University, and colleagues, ultimately found that those in the early intensive treatment group (n = 104) had a mean 5-year change in EDSS score of 0.3 (standard deviation [SD], 1.5) compared to the moderate-efficacy DMT escalation group (n = 488), which had an EDSS score of 1.2 (SD, 1.5) that remained significant after adjustment (95% CI, –1.38 to –0.32; P = .002). The median time to sustained accumulation of disability for the early intensive group was 6.0 years (95% CI, 3.17 to 9.16) compared to 3.4 years (95% CI, 2.77 to 4.00) for the escalation group (P = .05).

Individuals who underwent early intensive therapy were more likely to receive alemtuzumab (n = 70; 67%) than natalizumab (n = 34; 33%), while those who received high-efficacy therapy as second-line treatment (part of an escalation algorithm) were more likely to receive natalizumab (n = 43; 74%) than alemtuzumab (n = 15; 26%). In the overall cohort, 61 patients received fingolimod, and in the sensitivity analysis, 2 were reclassified to the intensive group and 59 were classified as escalated from moderate- to high-efficacy DMT. For those in the escalation group who escalated to a high-efficacy DMT as second-line treatment, the median time to sustained accumulation of disability was 3.3 years (95% CI, 1.8–5.6; comparison to the intensive group, P = .08).

For more coverage of MS Virtual 2020, click here.

REFERENCES
1. Iaffaldano P, Lucisano G, Caputo F, et al. Comparison of disability trajectories in relapsing Multiple Sclerosis patients treated with early intensive or escalation treatment strategies. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract PS01.04.
2. Harding K, Williams O, Willis M, et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol. Published online February 18, 2019. doi: 10.1001/jamaneurol.2018.4905.