The US experience of natalizumab - both very telling and very important to tell

CNS Drugs. 2015 Jun 26. [Epub ahead of print]
Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.
Johnson BH, Bonafede MM, Watson C.

BACKGROUND: Multiple sclerosis (MS) registry data, primarily from Europe, suggest that treatment with natalizumab delays time to relapse compared with platform therapy (interferon beta/glatiramer acetate).

OBJECTIVE:This study uses US administrative claims data and propensity score matching (PSM) to compare relapse rates and time to relapse among patients with MS using either platform therapy or natalizumab.

METHODS:Adults with MS receiving either platform therapy or natalizumab between January 1, 2009 and April 1, 2012 were identified in the Truven Health MarketScan® Research Databases. Patients were included if they had 12 months of continuous enrollment both before and after the index date (the first claim for either drug cohort) and had 12 months of claims data suggesting consistent treatment adherence during the follow-up period. Characteristics used in PSM included demographics, selected comorbidities and concomitant medications, MS severity, baseline relapse rates, and expenditures. A relapse was defined as an MS-related hospitalization or corticosteroid use.

RESULTS:A total of 882 patients were matched. Relapse occurred among significantly fewer patients in the natalizumab group (26.5 %) than platform therapy (35.5 %, p < 0.001) (hazard ratio 0.69; 95 % CI 0.59-0.82). Relapses were also significantly later for those on natalizumab (308 vs 283 days without relapse, p < 0.001).

CONCLUSION:Treatment with natalizumab was associated with a significantly lower risk and rate of MS relapse and longer MS relapse-free time compared with platform therapies.

Probability of no relapse: natalizumab vs. platform therapy

The platform therapies were IFNβ-1a (AVONEX®, REBIF®), IFNβ-1b (BETASERON®, EXTAVIA®), and glatiramer acetate (COPAXONE®). Natalizumab significantly reduced the risk of relapses both in terms of relapses (those on the platform therapy were 34% more likely to relapse) and longer relapse-free periods (nearly a month longer without a relapse). Within the 12-month post-natalizumab treatment period, those on natalizumab had significantly less steroid use and fewer MS-related inpatient admissions.

None of these findings are unexpected, the results from the Phase III AFFIRM study showed that annualized relapse rate reduced by 68% at year 1 and a 42% reduction in the risk of confirmed disability progression at 12 weeks. However, few studies have ever evaluated real life experience outside of clinical trials. And this work confirms that results from clinical trials do translate well into the real world.

There are a few important considerations. First, the disease severity of the patients in each arm, with more severe/complicated cases being channeled into natalizumab therapy in the first place, which may underestimate the impact of natalizumab on the study outcome. Secondly, the study population is limited to those with commercial health coverage or private Medicare supplemental coverage, questioning the generalizability of the findings to all MS patients.

As a general comment, I feel treatment expectations do not stop with natalizumab.

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