(Posted By: Josi Creek) Multiple sclerosis patients who took the oral investigational agent fingolimod were better able to maintain activities of daily living over a year than those treated with injected interferon beta-1A, according to a study presented here. Patients taking the standard injected therapy interferon beta-1A (Avonex) had more pronounced decline in their ability to perform ADLs based on a patient reported activity scale -- dropping by 0.43 points over 12 months, compared with those on either of two doses of fingolimod, whose scores dropped by just 0.08 and 0.12 points (P<0.05 for both comparisons), Jeffrey Cohen, MD, of the Neurologic Institute of the Cleveland Clinic in Cleveland, Ohio, reported. Fingolimod has previously been shown to reduce multiple objective measures of disease activity in patients with relapsing-remitting MS, as part of the TRANSFORMS study, which compared fingolimod to interferon beta-1A, Cohen said here at the meeting of the Joint Consortium of Multiple Sclerosis Centers and America's Committee on Treatment and Research in Multiple Sclerosis. The current study is a tertiary analysis from that study. Fingolimod modulates sphingosine-1-phosphate receptors on lymphocytes, blocking their exit from the lymph node, and thus reducing self-reactive lymphocytes in the central nervous system, Cohen explained. Patients in the study were randomized to receive daily oral fingolimod at either 0.125 mg or 0.5 mg, or 30 μ of intramuscular interferon beta-1a, for 12 months. All patients concurrently received a placebo treatment matching the other treatment arm. The three treatment groups were matched for mean age (36 years), disease duration (mean seven years), recent relapses, and disability. The effect of treatment on activities of daily living was measured with the PRIMUS scale, a patient self-reported measure developed with patient input. The scale comprises 15 items covering numerous domains, such as ability to do light jobs around the house, climb a flight of stairs, or prepare food, and has been validated for use in clinical trials. Each question is scored either 0 (no limitations), 1 (activity performed with difficulty), or 2 (cannot perform the activity), for a minimum score of 0 and a maximum of 30. The scale was administered at baseline, six months, and 12 months. Because the scale was not available in the language of all participating countries, only 909 of the 1,292 patients in the TRANSFORMS study participated, and 832 completed the 12-month evaluation. Baseline PRIMUS scores were "overall quite low," Cohen said, with mean scores of 3.2, 3.2, and 3.0, in the low-dose fingolimod, high-dose fingolimod, and in the interferon groups, respectively. Low-and high-dose fingolimod were superior to interferon beta-1A not only in total change from baseline, but also in the percentage of patients who improved on the PRIMUS scale during the 12 months (17.5%, 19.5%, and 14.1% respectively), and the percent who worsened (17.9%, 19.6%, and 24.1%, respectively). But, Cohen noted, the baseline disability of the patients was "quite mild," and "the overall magnitude of mean change was quite small in all three groups." "The trial was of relatively short duration, and a longer follow-up will be needed to obtain more clinically meaningful results," he said. Rock Heyman, MD, of the Department of Neurology at the University of Pittsburgh School of Medicine, commented that a quality-of-life scale is valuable in MS. The standard measures of MS progression, including even relapse rates, "may mean a lot to neurologists," he said, "but may not mean as much to patients," who are likely more interested in those aspects directly measured by quality-of-life scales. The results on the PRIMUS scale in this trial indicate the medicine "is helping to preserve day-to-day function," he continued. "Patients want to see everything else as well, but they want to know, 'how am I going to feel after a year?'" Heyman did not recommend that quality-of-life measures be the major outcome of trials, since they do not directly measure disease modification, "but they are very important and should be taken into account." An FDA advisory panel is meeting on Thursday to decide whether to recommend fingolimod for approval.

Labels: Avonex, Study