Nearly one-quarter of the 5, 384 patients enrolled, particularly those new to treatment, experienced a decrease of at least one point in the expanded disability status scale (EDSS), which is a standard measure of such improvement. The study, “Real-world disability improvement in patients with relapsing-remitting multiple sclerosis treated with natalizumab in the Tysabri Observational Program,” was published in the Multiple Sclerosis Journal. Tysabri works to treat multiple sclerosis (MS) by stopping inflammatory immune cells from entering the brain. In clinical trials, including the Phase 3 AFFIRM study (NCT00027300), it was shown to reduce relapse rates and lower the number of brain lesions.
Data in the AFFIRM trial also indicated that Tysabri could lead to a lessening in disability, but this potential benefit has not been a focus of RRMS clinical trials, the researchers reported. The Tysabri Observational Program (TOP, NCT00493298) is an ongoing observational study aiming to characterize the long-term safety of Tysabri, as well as the therapy’s effect on disease activity and progression. TOP is sponsored by Biogen, the company that developed and markets Tysabri, and opened in June 2007.
Researchers assessed data from July 2007 through Nov. 1, 2018, looking specifically at the extent to which patients showed in an exam confirmed disability improvement (CDI) — a one-point or greater decrease on EDSS — from their EDSS score recorded at the study’s start (a baseline measure).
These follow-up exams were given every 24 weeks (about six months) after baseline.
All RRMS patients analyzed had an EDSS score of at least two prior to starting with Tysabri. (EDSS measures disability on a score from zero to 10, with lower numbers indicating lesser disability.) In total, 1,287 (23.9%) patients experienced CDI, with more than half (51.8%) showing that one-point drop within the first year of treatment. Among those achieving CDI, a majority (56.6%) recorded an EDSS decrease of at least 1.5 points, and 34.4% a decrease of at least two points.
“This analysis of TOP shows that RRMS patients receiving natalizumab may experience disability improvement after treatment initiation,” the researchers wrote. “Nearly one-quarter of patients in TOP experienced a CDI event while on natalizumab.”
Statistical analyses suggested that those given Tysabri as a first disease-modifying therapy (DMT) were “significantly more likely to experience CDI than those treated with 1 prior DMT,” they added.
Other factors favouring CDI were younger ages at MS diagnosis, patients fairly new to MS (“fewer years” since diagnosis), and those who had more relapses in the year before starting Tysabri and higher baseline EDSS scores. The overall probability of achieving CDI after eight years of treatment was 33.2%, and the probability of maintaining such improvement for at least eight years was 52.6%. CDI maintenance was significantly more likely in patients with a larger reduction in EDSS scores. In total, 876 of 1,287 patients (68.1%) who reached CDI maintained the status over the duration of their follow-up.
Among people with a subsequent disability worsening after CDI, the average length of CDI was 3.4 years. Additionally, the overall average change in EDSS score was zero — that is, on average, disability returned to pre-treatment levels, rather than worsening further.
Disability was also assessed in the study according to functional systems (FS), which including sensory, visual, and mental abilities. Each FS is scored from zero to five or six; and as in the overall EDSS, higher scores indicate greater impairment.
After eight years of treatment with Tysabri, the overall probability of improvement (decrease) of at least one point in any FS domain was 88.8%.
The probability for functional improvements in specific abilities ranged from 38.3% (pyramidal system, difficulty moving limbs) to 58.6% (visual system, sight problems). In each FS, more than half of patients with FS improvement maintained it over the duration of follow-up.
“Improvements across all FS demonstrate the range of functional improvement,” the researchers wrote.
Similar to CDI, gains in functional systems were significantly more likely in patients for whom Tysabri was their first DMT.
“These results highlight disability improvement as a potential benefit of natalizumab treatment,” the researchers concluded.
“The potential for substantial, long-lasting disability improvement with natalizumab treatment should be considered when evaluating treatment choices for RRMS.”
Four of this study’s nine authors are Biogen employees; their work was conducted on “behalf of the TOP investigators.” Marisa Wexler, MS