Author Of 1 Presentation
PS01.04 - Comparison of disability trajectories in relapsing Multiple Sclerosis patients treated with early intensive or escalation treatment strategies
- P. Iaffaldano
- G. Lucisano
- F. Caputo
- D. Paolicelli
- F. Patti
- M. Zaffaroni
- V. Brescia Morra
- C. Pozzilli
- G. De Luca
- M. Inglese
- G. Salemi
- C. Florio
- E. Cocco
- P. Sola
- G. Lus
- A. Conte
- M. Amato
- F. Granella
- S. Galgani
- D. Centonze
- R. Totaro
- M. Rovaris
- M. Salvetti
- R. Mantegazza
- R. Bergamaschi
- D. Maimone
- E. Scarpini
- A. Bertolotto
- G. Comi
- M. Filippi
- M. Trojano
Abstract
Background
to date, no consensus exists on how aggressively and timely treat relapsing-remitting multiple sclerosis (RRMS) patients.
Objectives
To evaluate disability trajectories in a cohort of RRMS patients stratified according to two different disease modifying therapy (DMT) strategies, early intensive treatment (EIT) or moderate-efficacy treatment followed by escalation to higher-efficacy DMT (ESC).
Methods
RRMS patients with ≥5-year follow-up and ≥3 visits after start DMT, and a first visit within 3 years from disease onset were selected from the Italian MS Registry. EIT group included patients who received, as first DMT, fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group included those who received the high efficacy DMT after ≥1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score(PS)-matched for characteristics at the first DMT. The follow-up time from the first DMT start has been segmented into 12-month periods. The disability trajectories were evaluated by applying a longitudinal model for repeated measures with an autoregressive variance-covariance structure. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual EDSS changes compared to baseline values (delta-EDSS) in EIT and ESC groups.
Results
The study cohort included 2,652 RRMS patients from 62 Italian MS centers. The PS matching procedure produced 365 pairs. The median (IQR) follow-up after the first DMT start was 8.5 (6.5–11.7) years. All of the ESC patients escalated to a higher-efficacy DMT after a median time of 5.1 (3.1–8.4) years. The estimated baseline EDSS with relative confidence interval (95% CI) value was 2.52 (2.33-2.71) in the ESC group and 2.45 (2.26-2.64) in the EIT group. Mean delta-EDSS at each 12 month period were all significantly (p<0.02) higher in the ESC group compared to the EIT group. In particular, the mean delta-EDSS differences between the two groups tend to increase from 0.1 (0.01-0.19, p=0.03) at 1 year to 0.30 (0.07-0.53, p=0.009) at 5 years and to 0.67 (0.31-1.03, p=0.0003) at 10 years.
Conclusions
Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression and the effect tends to increase over time despite patients in the ESC group escalated to a higher-efficacy DMT.
Author Of 1 Presentation
P0039 - Circulating microRNAs as potential inflammatory biomarkers of acute exacerbation in relapsing-remitting multiple sclerosis (ID 938)
Abstract
Background
Multiple sclerosis (MS) is a chronic immune-mediated inflammatory-degenerative disease of the central nervous system. MicroRNAs (miRNAs) are short sequences of 19-25 non-coding single-stranded RNA nucleotides that regulate transcriptional gene expression by inhibiting the translation of specific messenger RNA targets and protein expression respectively. miRNAs are involved in various physiological and pathological processes, in particular contribute to the activation of the Th1 and Th17 pathways that regulate the immune response. Many studies show that the miRNAs are involved in MS epigenetic mechanisms affecting both the expression of inflammatory cells and myelination factors.
Objectives
This study aimed to compare the serum miRNAs in relapsing MS patients compared to remitting ones and to healthy controls for better understanding of MS pathogenesis.
Methods
We evaluated 3 groups of subjects: 16 relapsing-remitting (RR)MS patients in relapse (Group I); 12 RRMS patients in remission (Group II) and 12 sex- and age-matched healthy controls (Group III). Total extraction of RNA from sera was performed with a column-based method that includes small RNAs and minimizes the carryover of enzyme inhibitors typically contained in biofluids (miRNEeasy serum/plasma kit, QIAGEN). Total RNA was labeled and hybridized with Human miRNA Microarray Release 21 (Agilent) containing probes for 2549 human microRNAs from the Sanger database. Arrays were verified for quality control and extracted by Agilent Feature Extraction 10.7.3.1 software and entirely processed by MATLAB (The MathWorks Inc.) in house-built routines. Deregulated miRNAs were established by permutation test and a false discovery procedure used for multiple comparisons. Unsupervised hierarchical clustering was performed to individuate specific pattern of expression among samples and clusters of miRNAs. The results obtained were validated by Real-Time PCR.
Results
We analyzed 2549 miRNA that were expressed in at least 50% of the samples. After eliminating 10 samples that expressed only a few of these miRNAs, we found 66 expressed miRNAs in the half of remained samples. Microarray analysis identified a signature of 8 deregulated miRNAs in relapsing MS patients compared to controls and remitting MS patients. In particular, among these eight miRNAs, two were up-regulated (miR-2861 and miR-6821-5p) while six were down-regulated (miR-4281, miR-5196-5p, miR-6076, miR-642a -3p, miR-671-5p, miR-6879-5p).
Conclusions
We have found several upregulated or downregulated miRNA to be correlated with disease exacerbation in RRMS patients. Previous studies have reported five of these miRNAs to be involved in other inflammatory disorders. We hypothesize that the miRNA could be useful biomarkers not only to improve diagnosis and disease control, but also to predict the phase of acute exacerbation in MS.