BARCELONA — Use of four no evidence of disease activity (NEDA-4) criteria better predicted disability-related outcomes in relapsing-remitting multiple sclerosis (RRMS) than the three criteria (NEDA-3) approach, data indicate.
Ludwig Kappos, MD, of the University Hospital of Basel in Basel, Switzerland, and fellow researchers conducted the post-hoc analysis, which was presented at the European Committee for Treatment and Research in Multiple Sclerosis Congress in Barcelona.
NEDA concepts are increasingly considered in the evaluation of disease evolution and treatment efficacy in RRMS. The three concepts of NEDA-3 are no magnetic resonance imaging (MRI) lesion activity; no relapses; and no confirmed progression of disability (CDP). In NEDA-4, however, another criterion is added — annual brain volume loss (BVL) <0.4% — which Dr. Kappos and colleagues said provides a more comprehensive assessment of disease activity and worsening and structural damage.
The study included patients (n=2,355) from the FREEDOMS and FREEDOMS II trials who were treated with 0.5 mg or 1.25 mg of fingolimod in the core studies or their extensions. At one year, Dr. Kappos and colleagues evaluated 1,659 patients for NEDA-3 and 1,306 for NEDA-4, and the status of both significantly predicted disease course during the following six years.
Specifically, compared with patients who achieved NEDA-3 status at one year, those who did not were at increased risk for relapse (HR=2.16; P<.0001); six-month CDP (HR=1.4; P=.0047); either relapse or six-month CDP (HR=1.79; P<.0001); and reaching Expanded Disability Status Scale (EDSS) ≥6 (HR=1.6; P=.0126) during the subsequent six years. For patients not achieving NEDA-4 status at one year, they also were at increased risk in the following six years for relapse (HR=1.81; P<.0001); six-month CDP (HR=1.61; P=.0006); either relapse or six-month CDP (HR=1.72; P<.0001); and reaching EDSS ≥6 (HR=2.85; P<.0001).
In addition, patients failing NEDA-3 status had HRs for MRI activity of 2.89 and 1.51 for annual BVL ≥0.4%; and for those failing NEDA-4, they had HRs of 2.39 for MRI activity and 2.94 for BVL ≥0.4% (P for all <.0001). Similar results were reported for the predictive value of NEDA-3 and NEDA-4 during the first two years of treatment.
“NEDA-3 status seems to correlate more with subsequent relapse and focal inflammatory MRI activity, while NEDA-4 (which adds an imaging outcome that captures tissue destruction as a result of both focal and diffuse pathology) tended to be a better predictor of subsequent disability-related outcomes and BVL,” Dr. Kappos and colleagues wrote. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for RRMS.”
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- Kappos L et al. Abstract 116. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.