Monday, 9 March 2015

Relapse activity and natalizumab persistence

Natalizumab does what it says on the tin: real-life data. #MSBlog #MSResearch

"The following study, using a medical insurance database, shows that persistent use of natalizumab is associated with lower relapse rates and lower healthcare utilization. Is this surprising? Not really; we showed this in the pivotal AFFIRM trial. This study reassuringly shows that real-life data mirrors that which was collected in the pivotal trial. It is a pity we don't have more real-life data from this database; relapse rate is a poor proxy of efficacy and it would be nice to know how persistence of natalizumab usage impacts on quality of life, employment, anxiety and depression, fatigue, sleep, bladder function, etc. in real-life."

"Those of us who work in the field of MS, often discuss the pre and post-natalizumab era. Natalizumab, the first of the high-efficacy drugs, to be licensed to treat MS has been transformational; particularly when used early. Not only does it achieve NEDA (no evident disease activity) in  the majority of treated MSers when you re-baseline the MRI at 12 months, but a substantial proportion of MSers get an improvement in function. New MRI data has also emerged to show that natalizumab reduces end-organ damage (brain atrophy). The problem we have in the UK is that MS is generally managed by MSologists (MS experts) and hence our general neurology colleagues have not experienced the transformation natalizumab, and other high-efficacy drugs, have had on the management of relapsing MS. As a result of this we still see significant delays in getting to see MSers with active disease who may be eligible for natalizumab and other therapies early on. The concept of early effective treatment to prevent or delay the onset of progressive disease has yet to be adopted by the wider neurological community. Fortunately, when I travel to other countries, for example Australia, this is not necessarily the case. Maybe when we see data that MSers in Australia do better than MSers in Europe and the UK it will change practice. Nothing like a league-table to force change."

Real-life data

McQueen et al. Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study. J Manag Care Spec Pharm. 2015 Mar;21(3):210-8.

BACKGROUND: Natalizumab disease-modifying therapy for RRMS is efficacious in randomized controlled trials. Few studies have estimated the association between real-world natalizumab persistence behavior and relapse-related outcomes.

OBJECTIVES: To (a) examine the impact of using natalizumab consistently (i.e., persistent) on relapse-related outcomes as compared with transitioning to inconsistent natalizumab use (i.e., non-persistent) and (b) examine the impact of other treatment patterns on relapse-related outcomes for those who initiated natalizumab. 

METHODS: Using the IMS PharMetrics Plus claims database (years 2006-2012), we identified MSers who initiated natalizumab (no natalizumab claims in year prior) and had at least 2 years of follow-up. Persistence in annual follow-up periods was defined as no 90-day or greater gap in natalizumab therapy. Relapse was an MS-related hospitalization or outpatient visit with intravenous or oral steroid burst claim within 7 days. Analyses compared observations based on changes in natalizumab persistence and natalizumab non-persistence status from 1 year to the next (e.g., transitioning from persistent to non-persistent), estimating differences in mean annual relapses and mean annual relapse-related costs. 

RESULTS: A total of 2,407 natalizumab initiators had at least 2 years of follow-up, yielding 4,770 year-to-year natalizumab treatment patterns where each subject contributed 1, 2, or 3 year-to-year treatment patterns. In the year prior, 3,187 treatment patterns were persistent; 731 (22.9%) of these transitioned to non-persistence. The remaining 1,583 treatment patterns were non-persistent in the year prior; 132 (8.3%) of these transitioned to persistence. Persistent to non-persistent treatment patterns were associated with a mean relapse-rate increase of 0.23 (95% CI = 0.12, 0.35), and a mean increase in relapse-related costs of $1,346 (95% CI = $97, $2,595). Non-persistent to persistent treatment patterns were associated with a mean relapse-rate decrease of -0.15 (95% CI = -0.32, 0.017) and a mean decrease in relapse-related costs of -$1,369 (95% CI = -$2,761, $23). 

CONCLUSIONS: Findings suggest that real-world persistent natalizumab users who become non-persistent have statistically significant increases in annual relapses and relapse-related costs. Those who transition from non-persistent to persistent have non-significant reductions in relapses and their associated costs.

CoI: multiple


  1. The first question that comes to mind - there is no information provided in this summary of this study as to the reasons WHY patients became "non-persistent". From what I've seen on this blog, anyone stopping Tysabri is best transitioned onto another DMT due to the already known rebound effects of stopping Tysabri. So, given the PML risks, and increased vigilance recommended for people on Tysabri, is this study actually really telling anyone anything new? I think it's just confirming what's already known, especially with PML risks meaning that more people are needing to stop Tysabri because of the PML risks.

  2. Prof G.
    Out of interest, when you say Tysabri reduces atrophy, are we talking about reduction to within the normal limits of aging? How does it stack up against Lemtrada in that regard?


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