#MSVirtual2020 – Early Intensive DMT Use in RRMS Appears More Effective Than Escalation

#MSVirtual2020 – Early Intensive DMT Use in RRMS Appears More Effective Than Escalation
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Early use of high efficacy disease-modifying therapies (DMTs) is more effective than the traditional approach — that of an escalating treatment regimen — at delaying disability progression in people with relapsing-remitting multiple sclerosis (RRMS), a real-life study from Italy reports.

People later moving to more aggressive treatment also appeared to benefit less from it than those treated intensively from the start, its researchers said.

These findings were presented by Pietro Iaffaldano, MD, with the University of Bari Aldo Moro at the MSVirtual2020 conference held Sept. 11–13. This was the 8th joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Iaffaldano’s oral presentation was titled “Comparison of disability trajectories in relapsing Multiple Sclerosis patients treated with early intensive or escalation treatment strategies” (abstract #PS01.04).

Among health professionals, no consensus now exists as to how aggressively RRMS patients should be treated.

The traditional and most frequently used approach in treating RRMS supports the use of moderately effective DMTs, which generally have good safety profiles. Patients then move to higher-efficacy DMTs as needed, according to disease progression.

While high-efficacy DMTs for RRMS have a consistently superior effect on disease activity than the traditional first-line MS DMTs, they are usually associated with greater risks. For this reason, they are often reserved for high-risk patients with poor prognosis.

However, increasing data suggest that RRMS patients may benefit more from upfront use of the most efficacious DMTs — an approach called early intensive therapy, or EIT — than from the standard escalating regimen (ESC). EIT may manage the disease in its early, inflammatory phase, preventing irreversible damage and long-term disability.

Researchers in Italy evaluated the long-term disability trajectories of a large group of RRMS patients treated with EIT or a standard escalating regimen in a real-life setting.

“Whether patients initiating high-efficacy DMTs as their 1st therapy derive a greater long-term benefit on disability progression than those who start with the 1st-line agents and then switch to high-efficacy DMTs, remains a matter of debate,” Iaffaldano said.

A total of 2,652 RRMS patients, each with at least five years of follow-up, a first visit within three years of disease onset, and three or more disability assessments after starting a DMT, were selected from the Italian MS Registry.

Patients were treated and followed at 62 MS centers in that country, and their disability was measured through the expanded disability status scale (EDSS).

The EIT group included 365 patients treated with Gilenya (fingolimod, by Novartis), Tysabri (natalizumab, by Biogen), Novantrone (mitoxantrone), Lemtrada (alemtuzumab, by Sanofi-Genzyme), Ocrevus (ocrelizumab, by Genentech), or Mavenclad (cladribine, by EMD Serono) as a first disease-modifying treatment. (EMD Serono is known as Merck KGaA outside North America.)

The ESC group included 2,337 patients who moved to a high-efficacy DMT after at least one year of treatment with Copaxone (glatiramer acetate, by Teva Pharmaceuticals), various interferons, azathioprine (sold as Azasan and Imuran), Aubagio (teriflunomide, by Sanofi Genzyme), or Tecfidera (dimethyl fumarate, by Biogen).

The effectiveness of these two treatment approaches was then assessed by looking at mean annual changes in disability, via patients’ EDSS scores, for up to 10 years, as compared with scores before DMT initiation.

To help ensure valid comparisons, patients in the escalating treatment (ESC) group were matched as best as possible at baseline (therapy start) by characteristics like age, sex, EDSS scores, etc., to those in the early intensive treatment (EIT) group. In total,  the researchers looked at data covering 365 pairs of matching patients.

These people had mild to moderate disability, with a mean EDSS score of 2.61 in the EIT group and 2.63 in the ESC group, before starting a first DMT. Patients were followed by a median of 8.5 years (range of 6.5–11.7 years).

All in the escalating regimen moved to a higher-efficacy DMT after a median of 5.1 years (range: 3.1–8.4 years). Most (93.11%) had started with an injectable DMT (such as the interferons and Copaxone), before escalating to Tysabri (42.98%) or Gilenya (38.84%).

Among EIT patients, the most common first high-efficacy DMT used was Tysabri (40.77%), followed by Novantrone (38.84%).

Significantly higher annual EDSS changes were seen in ESC group patients than in those on the EIT regimen at each follow-up year, indicating faster disability progression in people on the standard escalating regimen.

Notably, EDSS score differences between the two groups increased from 0.10 at one year to 0.30 at five years, and to 0.67 at 10 years.

“Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression and the effect tends to increase over time despite patients in the ESC group escalated to a higher-efficacy DMT,” the researchers wrote.

“This could be due to a more potent effect on disability progression of the high-efficacy DMTs in the early years of the disease or alternatively, to the longer exposure to them,” Iaffaldano said.

He noted further studies are needed to confirm these results, and to establish the long-term safety of the EIT approach. Still, these findings may help clinicians making treatment decisions, “in particular in the cases of naive patients [those with no prior treatment] with poor prognosis factors at the onset of disease,” Iaffaldano added.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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