Biogen Idec announced that a post hoc analysis of data from the AFFIRM study shows Tysabri (natalizumab) significantly increased the proportion of relapsing-remitting multiple sclerosis (RRMS) patients with confirmed improvement in walking speed (CIWS) relative to placebo at two years.

Additional data from observational registry studies show that switching to Tysabri after experiencing a multiple sclerosis (MS) relapse while taking interferon beta (IFNß) or glatiramer acetate (GA) reduced the risk of future relapses and treatment discontinuation. These data were presented at the 66th American Academy of Neurology (AAN) annual meeting in Philadelphia, Pa. (April 26-May 3, 2014).

“We know that MS has a significant impact on ambulation a key concern for many people living with this disease which is why we analysed data from AFFIRM to evaluate the potential impact of Tysabri on walking speed,” said Alfred Sandrock, managing director, group senior vice president and chief medical officer at Biogen Idec. “Tysabri was associated with a 20 per cent increase in walking speed, a clinically relevant improvement, in a significantly greater number of patients compared to placebo.”

AFFIRM was a two-year, randomised, multi-centre, placebo-controlled, double-blind study of 942 patients with RRMS that evaluated the effect of Tysabri on the progression of physical disability and the rate of clinical relapses. A post-hoc analysis of AFFIRM assessed the impact of Tysabri on the proportion of patients with CIWS compared to placebo. CIWS was defined as =20 per cent increase in walking speed from baseline in the timed 25-foot walk (T25FW) confirmed 12 weeks later.

Results show that, over the course of two years, CIWS was significantly associated with improvement in patient-reported physical functioning. Treatment with Tysabri increased the proportion of patients with CIWS at year two by 79 per cent compared to placebo (Tysabri, 12.3 per cent  placebo 6.9 per cent  p=0.0133). These effects were more significant and occurred earlier in patients with more advanced disability with CIWS being increased by as much as five-fold compared to placebo at one year.

While many MS clinical trials measure disability progression, which includes a measure of ambulation by the Expanded Disability Status Scale (EDSS), these data from AFFIRM suggest that CIWS may be a more sensitive endpoint in capturing improved ambulation in RRMS patients.

Two additional studies used propensity-matched registry data to evaluate the effects of transitioning to Tysabri after an on-treatment relapse while taking INFß or GA, compared to remaining on, or switching between, INFß and GA. Results show that switching to Tysabri decreased the risk of future relapses, disability progression and treatment discontinuation for MS patients.

Because there are no randomised clinical trials comparing treatment options for patients with ongoing disease activity, comparisons of propensity-matched data from large observational cohorts are useful to estimate the relative risks associated with treatment decisions in a clinical setting. In these studies, researchers matched patients across three large observational clinical trials: Tysabri Observational Programme (TOP), an ongoing observational, open-label, 10-year prospective study of relapsing-remitting MS (RRMS) patients; MSBase, an ongoing, longitudinal database open to all practicing neurologists worldwide; and MSCOMET, a longitudinal MSBase registry substudy assessing the efficacy of IFNß and GA in 1,000 patients in 14 countries.

In the first study, researchers matched 759 MS patients who participated in the MSCOMET study to the same number of patients in the TOP. They assessed time to first relapse, treatment discontinuation and disability progression over one year in those who relapsed on IFNß or GA in the 12 months prior to study entry and either transitioned to Tysabri or stayed on their original first-line therapy. Data show that switching to Tysabri versus remaining on IFNß or GA after an on-treatment relapse decreased the risk of relapse by 57 per cent and reduced the risk of treatment discontinuation by 52 per cent. Researchers also analysed a smaller subset of patients (n=227 patient pairs) to assess disability progression. They found the incidence of three-month confirmed disability progression was lower in patients who transitioned to Tysabri than in those who persisted on IFNß or GA; however, this difference was not statistically significant, likely due to the small sample size and small number of observed progression events.

In the second study, researchers compared annual relapse rate, treatment discontinuation and disability progression over one year within two subgroups of patients who participated in MSBase and the TOP: subgroup one, patients taking IFNß who switched to GA compared to those who switched to Tysabri (n=578 for each cohort); and subgroup two, patients taking GA who switched to IFNß compared to those who switched to Tysabri (n=165 for each cohort). Results show that transitioning to Tysabri treatment versus switching from IFNß to GA reduced the risk of relapse by 63 per cent and discontinuation risk by 62 per cent. Transitioning to Tysabri treatment versus switching from GA to IFNß also reduced the risk of relapse by 53 per cent and discontinuation risk by 48 per cent. Researchers then combined the subgroups to assess three-month confirmed disability progression; results showed that transitioning to Tysabri versus switching between IFNß and GA reduced the risk of disability progression by 32 per cent.