Author Of 2 Presentations
P0092 - Incidence of recurrence of disease activity after fingolimod discontinuation in older patients (ID 264)
Abstract
Background
Discontinuing fingolimod (FTY) in older patient is a growing concern with little evidence supporting the decision to pursue treatment and reasonable doubt for disease reactivation after withdrawal.
Objectives
We investigate the incidence of RDA and rebound in MS patients who discontinued fingolimod for any reason, and looked for risk factors influencing this risk. Of particular interest was the subgroup of older patients who discontinued FTY for other reasons than disease progression. Our hypothesis was that these patients, older at treatment discontinuation, previously stable on treatment, would have a statistically lower risk of recurrence of activity given their age.
Methods
Retrospective analysis of 288 MS patients on FTY. Recurrence of disease activity (RDA) was defined as the occurrence of either clinical and/or MRI activity in the 6 months after FTY withdrawal; among these patients with RDA, we considered rebound when the levels of disease activity surpassed pretreatment activity. We defined a subgroup of patients older than ≥ 50 years at FTY discontinuation and with NEDA-3 status during FTY treatment.
Results
128 patients discontinued FTY from 2011 to 2019 mainly for estimated high PML risk (3.6%), inefficacy (26.6%) or pregnancy planning (18%). RDA occurred in 45 patients (35.2 %) within 3.4 months (SD 2). Younger age at disease onset (p=0.008), highly active disease at baseline (p=0.037) and previous treatment with natalizumab (p=0.050) increased the risk of RDA at FTY discontinuation. Sixteen patients (12.5%) experienced rebound with a mean of 9 Gd enhancing lesions. Baseline MRI activity (p=0.008) and longer wash-out period (p=0.001) correlated with rebound. Twenty-two patients were older than 50 years at FTY withdrawal and discontinued FTY for other reasons than disease progression. The incidence of RDA was lower, yet not statistically significant, from younger patients (18.2 % RDA, p=0.068).
Conclusions
RDA occurred in 35.2% of our patients including 12.5% with rebound. Older age at FTY discontinuation may be associated with a lower risk of disease reactivation, although the incidence of RDA remains high, as 1/5 of the older patients, previously stable on treatment, experienced RDA.
P0099 - Is disease activity prior to fingolimod initiation in treatment-naive patients predictive of response? (ID 323)
Abstract
Background
Randomized controled trials, post-hoc analysis and real-world post-marketing studies have confirmed fingolimod (FTY) efficacy over placebo as second-line therapy in case of persistent disease activity and in treatment-naive patients with rapidly evolving highly active RR-MS. In countries where fingolimod is available as first-line therapy without restrictions, we have an opportunity to observe long-term efficacy profile of this drug in treatment-naive patients according to their initial disease activity.
Objectives
To evaluate and compare the incidence of NEDA-3 status at last follow up according to the baseline MS disease activity.
Methods
Retrospective analysis of clinical and radiological data of 54 RR-MS patients treated with FTY. The patients were divided into highly active patients (HΑ) if ≥ 2 relapses in the year before treatment initiation and ≥1 Gd-enhancing T1 lesion or “not highly active” (NHA). NEDA-3 status at endpoint was defined as no relapses, no EDSS progression and no new T2 or Gd-enhancing lesions during the follow-up.
Results
Mean follow-up duration was 48.2, SD 18.4 months. FTY efficiently reduced relapses (NHA 90.3% reduction, p<0.001, HA 84.9%, p<0.001), and new Gd enhancing lesions (NHA 85.4% reduction, p=0.019, HA 92.3%, p=0.043). 53.7% reached NEDA-3 status at endpoint, although the distribution was different in the two subgroups with 62.2%, (n=23/37) of the NHA patients reaching NEDA 3 status compared to 35.3% (n=6/17) of the HA. The proportion of patients reaching NEDA-3 status decreased over time (first line : 80% at 2 years and 66% at 4 years, HA : 58% at 2 years and 38% at 4 years, p=0.042). 63% of patients were still on FTY at last follow-up (n=34/54). Main reason for discontinuation was lack of efficacy (75%, n=15/20).
Conclusions
Chances of reaching NEDA-3 status reduce over time with the highest relative benefit from FTY treatment observed when prescribed as a first line disease-modifying drug in treatment-naïve MS patients, which may favour its indication in that context rather than for HA patients only.
Presenter Of 2 Presentations
P0092 - Incidence of recurrence of disease activity after fingolimod discontinuation in older patients (ID 264)
Abstract
Background
Discontinuing fingolimod (FTY) in older patient is a growing concern with little evidence supporting the decision to pursue treatment and reasonable doubt for disease reactivation after withdrawal.
Objectives
We investigate the incidence of RDA and rebound in MS patients who discontinued fingolimod for any reason, and looked for risk factors influencing this risk. Of particular interest was the subgroup of older patients who discontinued FTY for other reasons than disease progression. Our hypothesis was that these patients, older at treatment discontinuation, previously stable on treatment, would have a statistically lower risk of recurrence of activity given their age.
Methods
Retrospective analysis of 288 MS patients on FTY. Recurrence of disease activity (RDA) was defined as the occurrence of either clinical and/or MRI activity in the 6 months after FTY withdrawal; among these patients with RDA, we considered rebound when the levels of disease activity surpassed pretreatment activity. We defined a subgroup of patients older than ≥ 50 years at FTY discontinuation and with NEDA-3 status during FTY treatment.
Results
128 patients discontinued FTY from 2011 to 2019 mainly for estimated high PML risk (3.6%), inefficacy (26.6%) or pregnancy planning (18%). RDA occurred in 45 patients (35.2 %) within 3.4 months (SD 2). Younger age at disease onset (p=0.008), highly active disease at baseline (p=0.037) and previous treatment with natalizumab (p=0.050) increased the risk of RDA at FTY discontinuation. Sixteen patients (12.5%) experienced rebound with a mean of 9 Gd enhancing lesions. Baseline MRI activity (p=0.008) and longer wash-out period (p=0.001) correlated with rebound. Twenty-two patients were older than 50 years at FTY withdrawal and discontinued FTY for other reasons than disease progression. The incidence of RDA was lower, yet not statistically significant, from younger patients (18.2 % RDA, p=0.068).
Conclusions
RDA occurred in 35.2% of our patients including 12.5% with rebound. Older age at FTY discontinuation may be associated with a lower risk of disease reactivation, although the incidence of RDA remains high, as 1/5 of the older patients, previously stable on treatment, experienced RDA.
P0099 - Is disease activity prior to fingolimod initiation in treatment-naive patients predictive of response? (ID 323)
Abstract
Background
Randomized controled trials, post-hoc analysis and real-world post-marketing studies have confirmed fingolimod (FTY) efficacy over placebo as second-line therapy in case of persistent disease activity and in treatment-naive patients with rapidly evolving highly active RR-MS. In countries where fingolimod is available as first-line therapy without restrictions, we have an opportunity to observe long-term efficacy profile of this drug in treatment-naive patients according to their initial disease activity.
Objectives
To evaluate and compare the incidence of NEDA-3 status at last follow up according to the baseline MS disease activity.
Methods
Retrospective analysis of clinical and radiological data of 54 RR-MS patients treated with FTY. The patients were divided into highly active patients (HΑ) if ≥ 2 relapses in the year before treatment initiation and ≥1 Gd-enhancing T1 lesion or “not highly active” (NHA). NEDA-3 status at endpoint was defined as no relapses, no EDSS progression and no new T2 or Gd-enhancing lesions during the follow-up.
Results
Mean follow-up duration was 48.2, SD 18.4 months. FTY efficiently reduced relapses (NHA 90.3% reduction, p<0.001, HA 84.9%, p<0.001), and new Gd enhancing lesions (NHA 85.4% reduction, p=0.019, HA 92.3%, p=0.043). 53.7% reached NEDA-3 status at endpoint, although the distribution was different in the two subgroups with 62.2%, (n=23/37) of the NHA patients reaching NEDA 3 status compared to 35.3% (n=6/17) of the HA. The proportion of patients reaching NEDA-3 status decreased over time (first line : 80% at 2 years and 66% at 4 years, HA : 58% at 2 years and 38% at 4 years, p=0.042). 63% of patients were still on FTY at last follow-up (n=34/54). Main reason for discontinuation was lack of efficacy (75%, n=15/20).
Conclusions
Chances of reaching NEDA-3 status reduce over time with the highest relative benefit from FTY treatment observed when prescribed as a first line disease-modifying drug in treatment-naïve MS patients, which may favour its indication in that context rather than for HA patients only.