Long-Term Efficacy of Fingolimod Reinforced by New NEDA-4 Analysis

BARCELONA—Data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) show that 31.2% to 44.8% of patients continuously treated with fingolimod in the FREEDOMS core and extension trials achieved NEDA-4 in each of the years three to seven. NEDA-4—no evidence of disease activity in the four areas of relapses, MRI lesions, brain atrophy, and disability progression—is a comprehensive measure of MS disease control. A separate analysis confirmed that NEDA-4 status in the first year is a better predictor of long-term outcomes than an assessment of three parameters (relapses, MRI lesions, and disability progression).

A follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with relapsing-remitting multiple sclerosis (MS). Bruce Cree, PhD, MD, of the University of California San Francisco, and colleagues found that in the first year, 27.1% of patients on fingolimod achieved NEDA-4, compared with 9.1% on placebo. Switching from placebo to fingolimod after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous fingolimod treatment, 31.2% to 44.8% reached NEDA-4 status in each of the years three to seven.

“Fingolimod showed sustained efficacy in achieving NEDA-3 and NEDA-4 over seven years,” Dr. Cree and colleagues reported. “Patients who were on placebo for the first two years demonstrated substantial improvements in NEDA-3 and NEDA-4 outcomes after switching to fingolimod. However, patients who received fingolimod from the start appeared to derive more benefit throughout the first five years.”

A separate follow-up analysis of data from the FREEDOMS and FREEDOMS II trials also confirmed for the first time that assessment of relapsing-remitting MS based on NEDA-4 allowed physicians to better predict long-term disability and brain shrinkage outcomes than just assessing relapses, MRI lesions, and disability progression. Ludwig Kappos, MD, of University Hospital in Basel, Switzerland, and colleagues found that NEDA-4 status over the first year was a significantly better predictor of disability and brain atrophy over the subsequent five years, as measured by patients reaching a stage of severe disability (EDSS of 6 or more) or having more than 0.4% mean annual brain volume loss. According to the researchers, these findings support the importance of assessing relapsing-remitting MS with NEDA-4 to enable a more reliable prediction of long-term disease outcomes.

“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 brain volume loss,” Dr. Kappos and colleagues said. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for relapsing-remitting MS.”

BARCELONA—Data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) show that 31.2% to 44.8% of patients continuously treated with fingolimod in the FREEDOMS core and extension trials achieved NEDA-4 in each of the years three to seven. NEDA-4—no evidence of disease activity in the four areas of relapses, MRI lesions, brain atrophy, and disability progression—is a comprehensive measure of MS disease control. A separate analysis confirmed that NEDA-4 status in the first year is a better predictor of long-term outcomes than an assessment of three parameters (relapses, MRI lesions, and disability progression).

A follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with relapsing-remitting multiple sclerosis (MS). Bruce Cree, PhD, MD, of the University of California San Francisco, and colleagues found that in the first year, 27.1% of patients on fingolimod achieved NEDA-4, compared with 9.1% on placebo. Switching from placebo to fingolimod after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous fingolimod treatment, 31.2% to 44.8% reached NEDA-4 status in each of the years three to seven.

“Fingolimod showed sustained efficacy in achieving NEDA-3 and NEDA-4 over seven years,” Dr. Cree and colleagues reported. “Patients who were on placebo for the first two years demonstrated substantial improvements in NEDA-3 and NEDA-4 outcomes after switching to fingolimod. However, patients who received fingolimod from the start appeared to derive more benefit throughout the first five years.”

A separate follow-up analysis of data from the FREEDOMS and FREEDOMS II trials also confirmed for the first time that assessment of relapsing-remitting MS based on NEDA-4 allowed physicians to better predict long-term disability and brain shrinkage outcomes than just assessing relapses, MRI lesions, and disability progression. Ludwig Kappos, MD, of University Hospital in Basel, Switzerland, and colleagues found that NEDA-4 status over the first year was a significantly better predictor of disability and brain atrophy over the subsequent five years, as measured by patients reaching a stage of severe disability (EDSS of 6 or more) or having more than 0.4% mean annual brain volume loss. According to the researchers, these findings support the importance of assessing relapsing-remitting MS with NEDA-4 to enable a more reliable prediction of long-term disease outcomes.

“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 brain volume loss,” Dr. Kappos and colleagues said. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for relapsing-remitting MS.”

BARCELONA—Data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) show that 31.2% to 44.8% of patients continuously treated with fingolimod in the FREEDOMS core and extension trials achieved NEDA-4 in each of the years three to seven. NEDA-4—no evidence of disease activity in the four areas of relapses, MRI lesions, brain atrophy, and disability progression—is a comprehensive measure of MS disease control. A separate analysis confirmed that NEDA-4 status in the first year is a better predictor of long-term outcomes than an assessment of three parameters (relapses, MRI lesions, and disability progression).

A follow-up analysis of pooled data from the FREEDOMS and FREEDOMS II core and extension trials was conducted to assess NEDA-4 each year for seven years in patients with relapsing-remitting multiple sclerosis (MS). Bruce Cree, PhD, MD, of the University of California San Francisco, and colleagues found that in the first year, 27.1% of patients on fingolimod achieved NEDA-4, compared with 9.1% on placebo. Switching from placebo to fingolimod after year two doubled the proportion of patients achieving NEDA-4 (12.7% to 27.4%) in year three. Of those patients on continuous fingolimod treatment, 31.2% to 44.8% reached NEDA-4 status in each of the years three to seven.

“Fingolimod showed sustained efficacy in achieving NEDA-3 and NEDA-4 over seven years,” Dr. Cree and colleagues reported. “Patients who were on placebo for the first two years demonstrated substantial improvements in NEDA-3 and NEDA-4 outcomes after switching to fingolimod. However, patients who received fingolimod from the start appeared to derive more benefit throughout the first five years.”

A separate follow-up analysis of data from the FREEDOMS and FREEDOMS II trials also confirmed for the first time that assessment of relapsing-remitting MS based on NEDA-4 allowed physicians to better predict long-term disability and brain shrinkage outcomes than just assessing relapses, MRI lesions, and disability progression. Ludwig Kappos, MD, of University Hospital in Basel, Switzerland, and colleagues found that NEDA-4 status over the first year was a significantly better predictor of disability and brain atrophy over the subsequent five years, as measured by patients reaching a stage of severe disability (EDSS of 6 or more) or having more than 0.4% mean annual brain volume loss. According to the researchers, these findings support the importance of assessing relapsing-remitting MS with NEDA-4 to enable a more reliable prediction of long-term disease outcomes.

“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 brain volume loss,” Dr. Kappos and colleagues said. “These findings support use of NEDA-4 as a more comprehensive and balanced measure for relapsing-remitting MS.”