Early High-efficacy Therapies May Be Better to Eliminate MS Activity
Using high-efficacy therapies as a first treatment for multiple sclerosis (MS) patients significantly increases the likelihood of having no evidence of disease activity after one and two years, compared to using moderately effective therapies, according to a real-world study of Norwegian patients.
However, with each additional attempted treatment, the odds were lower that high-efficacy therapies would outperform less potent ones.
“Our findings illustrate the importance of choosing the most effective drug at the time of diagnosis,” the researchers wrote.
The study, “Early High Efficacy Treatment in Multiple Sclerosis Is the Best Predictor of Future Disease Activity Over 1 and 2 Years in a Norwegian Population-Based Registry,” was published in the journal Frontiers in Neurology.
In recent years, several disease-modifying therapies (DMTs) have been developed to treat MS, which can effectively manage symptoms and slow the progression of disability.
Some DMTs are more effective at slowing progression — known as high-efficacy therapies — but carry a higher risk of serious side effects, whereas others are considered moderate-efficacy DMTs, with fewer side effects and a well-defined safety profile.
Current treatment guidelines recommend high efficacy therapies only for those with highly active disease, but it’s uncertain if starting highly potent DMTs at an earlier disease stage could provide greater benefits.
One tool used to measure the efficacy of an MS therapy is called “no evidence of disease activity” (NEDA) — defined as no relapses within a defined period of time, no evidence of disability progression, and no new or enlarging brain lesions on MRI scans.
Researchers based at the Oslo University Hospital in Norway have conducted a real-world study to determine how many Norwegian MS patients achieved NEDA after one and two years of DMT treatment and investigated the impact of their initial DMT in reaching NEDA.
Clinical and demographic data were collected from the BOT-MS database, which contains the medical records of all MS patients in two Norwegian counties as well as the capital, Oslo. The expanded disability status scale (EDSS) was used to measure disability.
All selected participants had been treated for at least 12 months with high efficacy DMTs — which included Tysabri (natalizumab), Gilenya (fingolimod), and Lemtrada (alemtuzumab) — and/or moderate-efficacy DMTs, such as interferons, Copaxone (glatiramer acetate), Aubagio (teriflunomide), and Tecfidera (dimethyl fumarate).
The study enrolled 694 participants, with a mean age at disease onset of about 30 years, and a total of 1,146 therapy initiations.
The analysis revealed that, in patients who started with a high-efficacy DMT, 68.0% achieved NEDA after one year, and 52.4% reached NEDA after two years. In contrast, in those who began with a moderate-efficacy DMT, 36.0% achieved NEDA at one year and 19.4% at two years. The effect of high- versus moderate-efficacy therapies to reach NEDA was highly significant at both time points.
Compared to moderate-efficacy DMTs, the odds of reaching NEDA at one year was 3.9 times higher with high-efficacy DMTs as a first medicine, and 4.6 times higher at year two. These odds were not affected by sex, age when therapy was first started, and the time from disease onset to treatment initiation.
Fewer patients achieved NEDA on high-efficacy medicines as a second therapy than as a first treatment, but the difference compared with moderate-efficacy therapies was still significant. In contrast, there was no difference between high- and moderate-efficacy DMTs for a third prescribed treatment.
Patients who achieved NEDA with high-efficacy DMTs were generally younger, and had a shorter time from onset to MS diagnosis, and time to beginning treatment. These findings were reversed for those on moderate-efficacy therapies. Also, reaching NEDA on a high-efficacy DMT as a first treatment was significantly more likely for patients with a medium or high risk of disease activity.
Individually, the high-efficacy DMTs Tysabri and Gilenya were significantly more likely to achieve NEDA after one and two years as a first medicine than interferons or Copaxone. The number of participants receiving Lemtrada was small, and all who were given this medicine as a second treatment reached NEDA.
Compared to interferons and Copaxone, Tysabri as a first medicine was 7.4 times more likely to achieve NEDA, which was more than all other therapies. The other moderate-efficacy therapies as a first medicine, Aubagio and Tecfidera, did not have better odds in reaching NEDA than interferons and Copaxone. These results remained after adjusting for sex, age at the start of treatment, time from disease onset to treatment, and risk group.
Finally, participants who first received a moderate-efficacy therapy were more likely to stop treatment than those on high-efficacy therapies (65.2% vs. 29.2%), primarily due to side effects (45% vs. 14%). The results were the same for the second therapy, but not for the third therapy.
“Achieving NEDA is significantly more likely in patients on high-efficacy disease modifying therapies than on moderate efficacy therapies, and the first choice of treatment is the most important,” the investigators concluded. “Moderate efficacy therapies should be used with caution in most MS patients, unless the clinician is confident the patient has a less active form of MS.”
“There is a need for updating immunomodulatory treatment guidelines ensuring early, high efficacy therapy for the majority of patients diagnosed with MS,” they added.