Tysabri Improves Cognition Over Long-term in Early RRMS Patients
Data about Biogen's treatment comes from the four-year observational STRIVE trial
Long-term treatment with Tysabri (natalizumab) significantly improves cognitive function and increases the chance of disability reduction in people with early relapsing-remitting multiple sclerosis (RRMS), according to data from the four-year observational STRIVE trial.
Patients on Tysabri also reported improved quality of life and less impact of MS on daily activities and work productivity.
These findings add to previously reported trial results showing that four years of Tysabri treatment were generally safe and reduced disease activity and the chance of experiencing disability progression.
Together, these results support the therapy’s long-term safety and efficacy in early RRMS patients in the real-world setting.
The study, “Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study,” was published in CNS Drugs. The work was funded by Biogen, which markets Tysabri.
Administered directly into the bloodstream, Tysabri is an antibody-based therapy widely approved for RRMS. It works by preventing immune cells from entering the brain and spinal cord, thereby preventing the damaging inflammation that drives MS.
Tysabri’s ability to slow disability progression and lessen disease activity has been well-documented across several clinical trials.
However, “prospective real-world studies examining the effect of long-term [Tysabri] treatment on cognitive processing speed, disability, and patient-reported outcomes in patients with early relapsing-remitting multiple sclerosis are limited,” the researchers wrote.
Cognitive processing speed is the amount of time it takes a person to take in information, process it, and then react to solve a problem or complete a task.
Now, researchers reported such effects based on data from the Biogen-sponsored, four-year observational STRIVE study (NCT01485003) of Tysabri. A total of 222 adults who had been diagnosed with RRMS in the prior three years were enrolled at 45 U.S. sites.
All participants were negative for antibodies against the John Cunningham virus (JCV), which causes a serious infection called progressive multifocal leukoencephalopathy (PML) that can occur in people using Tysabri.
155 complete the study
Participants were treated with Tysabri (300 mg every four weeks) for up to four years. A total of 155 patients (69.8%) completed the study, with 105 being on Tysabri for the entire four years.
The most common reason for stopping Tysabri was detection of antibodies against JCV or other risk factors for PML (27 patients); eight participants stopped the treatment due to lack of efficacy.
Data on the trial’s main goal and some secondary goals were reported previously. Nearly 74% of patients treated with Tysabri for four years achieved a state of no evidence of disease activity (NEDA), classified as the absence of relapse, new brain lesions, and disability progression.
The therapy also was associated with a 90.1% drop in annualized relapse rate and with a low cumulative probability of six-month confirmed disability worsening at four years (19.3%).
Newly published results concerned changes in cognitive processing speed, disability, quality of life, and patient-reported outcomes (PROs), including quality of life and the impact of MS on work productivity and regular activities over the four years.
SDMT assessment tool
Significant improvements in cognitive processing speed, as measured with the Symbol Digit Modalities Test (SDMT), were detected at all annual assessments.
Also, the proportion of patients on Tysabri for the four years who experienced a clinically meaningful improvement of at least four points on SDMT ranged from 44.8% after the first year to 63.8% at year four. Clinically meaningful improvements in cognitive processing speed after year one were maintained through year four in 83% of patients.
“STRIVE is the first study to show maintenance of a clinically meaningful improvement in SDMT score over 4 years of [Tysabri] treatment,” the researchers wrote.
Of the 133 patients with a score of at least two on the Expanded Disability Status Scale (EDSS) — indicating at least minimal disability at study’s start — 43 (32.3%) experienced six-month confirmed disability reduction at some point during the study.
Among these patients, 19 (44.2%) saw a reduction in EDSS score of at least two points, suggesting a fairly substantial reduction in disability.
Average scores on the physical and psychological domains of the Multiple Sclerosis Impact Scale (MSIS-29), a measure of quality of life, improved significantly at all annual assessments during the trial compared with values at study’s start.
At four years, scores of both quality of life domains were maintained or improved in more than 88% of patients.
Work productivity measured
The impact of MS on day-to-day activities and work productivity, as well as number of work hours missed per week, also was reduced significantly with Tysabri, as indicated by scores on the Work Productivity and Activity Impairment Questionnaire (WPAI).
Notably, among patients on Tysabri for the entire four years, these changes only reached statistically significance for MS impact on daily activities.
Exploratory analyses indicated that patients who saw an improvement in cognition or reduced disability (measured via SDMT and EDSS, respectively) also were more likely to report improvements on MSIS-29 and WPAI.
Most patients experiencing SDMT or EDSS improvements also achieved NEDA.
These results “highlight the benefits of long-term [Tysabri] treatment early in the RRMS disease course with respect to [confirmed disability reduction], cognitive processing speed, and PROs, including the impacts of MS on physical and psychological [quality of life] and on patients’ abilities to work and perform regular activities,” the researchers wrote.
“These findings further the understanding of improvements in other clinical outcomes with meaningful impact on MS patients’ daily lives while being treated with [Tysabri],” they added.
The team noted that this observational, open-label study was limited by the lack of any control group against which to compare RRMS patients on Biogen’s Tysabri.