Treatment with natalizumab (Tysabri, Biogen Idec and Elan) leads to improved language processing and retrieval of newly learned verbal material in patients with multiple sclerosis (MS), according to research presented here at the Consortium of Multiple Sclerosis Centers 24th Annual Conference and the Third Joint Meeting of Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers compared the effects of natalizumab with treatment with other disease-modifying therapies in patients with MS. The study included 46 patients taking natalizumab (mean ± SD age, 43.2 ± 9.1 years; mean ± SD years of education, 15.1 ± 2.5 years; 76% female; mean ± SD intertest interval, 14.9 ± 3.9 months; mean ± SD Expanded Disability Status Scale [EDSS] score, 3.8 ± 2.2; and disease duration <5 years, 9%; 5 – 10 years, 50%; and >10 years, 41%).
Investigators with South Shore Neurologic Associates of Patchogue, New York, and NeuroTrax Corporation of Newark, New Jersey, tested patients with a 30- to 60-minute computerized test designed to assess mild cognitive impairment (Mindstreams, NeuroTrax Corp). Patients were tested once, either before treatment or early in the treatment cycle (0-3 infusions), and again after the completion of more extended treatment (>9 infusions).
The comparison group included 37 stable patients, of whom 10 were receiving Avonex, 5 Betaseron, 5 Rebif, 5 CombiRX, 4 Copaxone, and 8 no treatment. In this group, mean ± SD age was 45.8 ± 10.8 years; mean ± SD years of education was 14.9 ± 3.6 years; 78% were female; mean ± SD intertest interval was 18.3 ± 5.0 months; mean ± SD EDSS score was 2.8 ± 1.8; and disease duration was less than 5 years for 32%, 5 to 10 years for 43%, and more than 10 years for 24%.
The researchers used repeated-measures analysis of variance (ANOVA) to assess improvements in EDSS, age- and education-adjusted cognitive domain scores, and raw data from individual tests. To measure effect size, the researchers computed Cohen's d (<.05 [1-tailed] was considered significant). The team used mixed-model ANOVA, controlled for EDSS, to analyze change over time between the groups.
There was improvement in the natalizumab group (P = .04, d = 0.21) but not the comparison group (P = .15, d = 0.11) in memory function, particularly verbal memory (natalizumab: .001 < P < .004; 0.43 < d < 0.55; comparison: .18 < P < .62; 0.02 < d < 0.14). The natalizumab group also showed improvement in verbal function (P = .005, d = 0.41), with no improvement seen in the comparison group (P = .31, d = 0.07). The improvements were seen in tests of matching (natalizumab: P = .01, d = 0.38; comparison: P = .17, d = 0.20) and rhyming (natalizumab: P = .01, d = 0.45; comparison: P = .94, d = 0.01). Similarly, EDSS scores improved (natalizumab: P = .03, d = 0.11; comparison: P = .26, d = 0.05).
"We did not expect to see improvements in cognition in this short period of time," Myassar Zarif, MD, a neurologist at South Shore Neurologic Associates who presented the research, told Medscape Medical News.
Dr. Zarif added that the NeuroTrax Mindstreams test, which was used in the study, proved useful. "Cognitive dysfunction is very difficult to assess in patients with MS. This test gives us data that is easy to apply, it's short, and it doesn't fatigue the patient," Dr. Zarif added.
"These quantitative neurologic tools give us a better idea as to what treatment failure is and what treatment success is. Tysabri is one of the treatments likely much more effective in suppressing [central nervous system] inflammation, and maybe it gives the brain a chance to recover. Maybe they will continue to get better as you shut down disease progression," Mark Gudesblatt, MD, director of the Comprehensive MS Care Center at South Shore Neurologic Associates, a coauthor of the research, told Medscape Medical News.
Dr. Gudesblatt was critical of the EDSS that is commonly in use, calling NeuroTrax a major improvement. "We're still using caveman neurology techniques to determine how we treat people."
Others were skeptical of the new technique. "I'd be interested in seeing further validation of NeuroTrax before it is put to wider use. It's relatively new, and we just don't know how accurate or sensitive it is," Keith Edwards, MD, director of the MS Center of Northeastern New York in Latham, who attended the session, told Medscape Medical News.
Dr. Edwards expressed skepticism about the fact that the study found improvements in language processing. "The conclusions of the study were surprising. Language issues are not the problem with MS. Usually, it's relatively preserved compared to processing speed and working memory, so the conclusions of the study strike me as possibly not valid."
The study was supported in part by NeuroTrax Corporation, Newark, New Jersey. Dr. Zarif, Dr. Gudesblatt, and Dr. Edwards have disclosed no relevant financial relationships.
Consortium of Multiple Sclerosis Centers 24th Annual Conference and the Third Joint Meeting of Americas Committee for Treatment and Research in Multiple Sclerosis: Abstract P05. Presented June 4, 2010.
