Multiple Sclerosis Relapses with Natalizumab Not Predictive

Among the new treatments to emerge for patients with relapsing multiple sclerosis (RMS), natalizumab (Tysabri/Biogen) has been popular. However, treatment with this drug is sometimes accompanied by episodic re-emergence of MS symptoms.

A new study found that such emergence of markers of inflammatory disease in the first year and second year of treatment with natalizumab had no significant effect on longer term disability progression.

Writing in PLOS, Joel Raffel, MD, and colleagues at Imperial College London, United Kingdom, reported they had studied 161 patients with RMS who started taking the drug from March 2007 through October 2010.

The subjects were followed for up to seven years so researchers could track changes in patients' standard disability score, known as the EDSS rating.

The team defined a relapse as an acute worsening of function that lasted at least 48 hours but one that was not related to having a fever or infection.

They found that 46 patients had a relapse in the first year and 28 had new MRI activity--new brain lesions seen on gadolinium enhanced scans.

These events in the first year of treatment predicted what patients' EDSS score would be at one year but not after years three to seven.

Patients with inflammatory activity on natalizumab were more likely to try other disease-modifying drugs, such as alemtuzumab, fingolimod, or cyclophosphamide.

But the switch did not change the trends observed in the study. "There was no significant difference in mean follow-up time between those with different Modified RIO Scores, or indeed any of the other inflammatory measures," they wrote.

Early relapses were a sign that patients could expect more such incidents in the short-term. Relapses in year 0—1 of treatment with natalizumab were correlated with the risk of further relapses in years one through three.

Thirty-five of 115 patients (30%) with no relapses in the first year reported relapses in years one through three.

In contrast, 31 out of 46 (67%) with relapses in the first treatment year reported relapses in years one through three.

But after three years, that effect disappeared, the team found.

Researchers have already looked at what early relapses predict in RMS patients taking interferons and glatiramer acetate, but this is the first study to look at the trend with natalizumab.

The authors acknowledge their study has shortcomings, including a small cohort size and a high average baseline EDSS rating. “The observational nature of this study means we cannot speculate whether patients might have gained greater benefit from other treatments," they added.

Randomized controlled interventional studies are needed to see whether patients who have such relapses should try other treatments--but they reiterate that such breakthroughs of symptoms do not necessarily mean treatments will not help in the long run.

The study is called "Inflammatory Activity on Natalizumab Predicts Short-Term but Not Long-term Disability in Multiple Sclerosis."