Author Of 2 Presentations
P0113 - MRI activity as a predictor of suboptimal response to natalizumab treatment: single center prospective cohort trial (ID 850)
Abstract
Background
Second line disease modifying drugs are widely used in clinical practice, the most common is natalizumab. NTZ have usually reduced the annualized rate of relapse and MRI lesion load in clinical trials but sometimes clinical and MRI activity was still present. Defining the predictors of suboptimal response is still needed to decide which second line treatment drug is optimal for patient.
Objectives
To determine the early clinical and MRI predictors of suboptimal treatment responses at one year of natalizumab (NTZ) therapy.
Methods
Clinical assessment (EDSS, relapses) and MRI (T2, T1Gd+) on start, after 6 and 12 months were made. All patients receive NTZ as second line therapy. RRMS patients undergoing treatment with NTZ for at least 12 months were classified as optimal responders if they have no EDSS score increase, no relapses and stable MRI (<3 new T2 and no Gd+(GELs)).Statistical analysis: one-way ANOVA, ROC-curve.
Results
43 patients (34 female) were included in analysis, RRMS, age–35.9-41.6 (95%CI) years, with disease duration of 58-131(95%CI) months;25-31(95%CI) NTZ infusions. On month 12 30.2% have a suboptimal response: 3 patient have a clinical relapse, 4–increasing of EDSS, 13–MRI activity. The comparison of the groups did not reveal statistically significant differences in age, sex, duration of the disease, duration of therapy before starting NTZ, relapse rate on baseline. Patients in suboptimal response group have more severe previous year MRI activity (before NTZ): more severe T2 lesion load (F=6.3,p=0.016) and high number of GELs (F=4.1,p=0.051). Predictors of suboptimal response are: more than 4 new T2 lesions during last year and more than 2 GELs on MRI before NTZ.
Conclusions
High previous year MRI activity is a strong predictor of suboptimal NTZ response. This cohort of patients probably needs more powerful therapy, for example, alemtuzumab or cladribine.
P0492 - Selective serotonin-reuptake inhibitors as potential add-on agents in relapsing-remitting multiple sclerosis patients with suboptimal response (ID 1004)
Abstract
Background
Suboptimal response for first line treatment of multiple sclerosis (MS) is one of the main challenges for real clinical practice. Presence of subthreshold activity suggests the possibility of switching to the second line of therapy, however, this is not always possible due to various reasons. Suboptimal response also could lead to increasing of patient’s reactive depression.
Objectives
To define the possibility of using SSRI (duloxetine or fluoxetine) for patients with suboptimal response on first-line injectable disease modifying therapy (DMT) to optimize response rate.
Methods
Clinical evaluation (EDSS, relapses), depression (Beck), MRI (T2&T1). Statistical analysis (nonparametric) – Wilkoxon test, Sign test. Inclusion criteria: 1) relapsing-remitting MS, 2) interferon beta (IFN) or glatiramer acetate (GA) during last 12 months, 3) suboptimal response for therapy defined by modified Rio Score (1 relapse during previous year without MRI activity OR +4-6 T2 lesions on MRI during previous year), 4) mild or moderate depression. Exclusion criteria: 1) progressive MS, 2) nonresponse defined by modified Rio Score and indication for switch to 2nd line, 3) severe depression, 4) severe comorbidity. Study design: visit 1 – baseline (EDSS, previous year relapses, MRI, depression scale), starting SSRI (duloxetine or fluoxetine); visit 2 – 1 year on SSRI + previous DMT (EDSS, previous year relapses, MRI, depression scale).
Results
Seventy patients (56 females), relapsing-remitting MS, age – 35,2 years [Q1:Q3; 28:42], duration of disease – 4,2 years [2:10], EDSS at visit 0 – 3.0 [2.4:3.6], DMT (GA–20, IFNb1b–30, IFNb1a–20) who met criteria at visit 1. Baseline relapse rate was 0.65 [95% confidence interval (CI) 0.61-0.70], dynamics of T2 lesion load during previous year +3.57 lesion [95%CI 2.6-4.8], EDSS dynamics during previous year - +0.27 [95%CI 0.24-0.31]. After 1 year of combined therapy (DMT+SSRI) relapse rate significantly decreased - 0.2 (T=180, p<0.001), no significant increase of EDSS level – minus 0.36 points. MRI activity also significantly decrease: numbers of new or newly enlarging T2 lesions were significantly reduced compared with the previous year: T2 lesion load increase only by 0.4 [95%CI 0.3-0.5] (T=51, p<0.001).
Conclusions
Adding SSRI (duloxetine or fluoxetine) to standard first line DMT for patients with suboptimal response could improve the response to the main DMT without switching to 2nd line.