Background and Aims:

How aggressively and timely treat relapsing-remitting multiple sclerosis (RRMS) is still a matter of debate.

To evaluate long-term disability trajectories in RRMS patients treated with two different therapeutic 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 disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received, as first DMT natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine, mitoxantrone,. ESC group patients received the high efficacy DMT after ≥1 year of injectables DMTs, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS)-matched for characteristics at the first DMT. A longitudinal model for repeated measures was applied to evaluate the disability trajectories. To estimate the effect of early versus late start of high-efficacy DMT the mean annual EDSS changes were compared to baseline values (delta-EDSS) in EIT and ESC groups.

Results:

2,702 patients were included in our study cohort. After PS matching procedure 363 pairs were retained. The median (IQR) follow-up was 8.5 (6.5–11.7) years. The ESC strategy was associated with a faster EDSS increase over time in comparison to the EIT (p<0.02). The mean delta-EDSS differences between the two groups increased 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 findings indicate a higher effectiveness of EIT than ESC strategy in slowing disability worsening over time.

Background and Aims:

Disability accrual in multiple sclerosis (MS) may occur as relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). We investigated the contribution of RAW and PIRA to confirmed disability accumulation (CDA) in patients with clinically isolated syndrome (CIS) and early relapsing-remitting (RR) MS.

Methods:

Relapsing-onset MS patients assessed within one year from onset and with follow-up >/= 5 years (n=5,340) were extracted from the Italian MS Registry. CDA was defined by an increase in Expanded Disability Status Scale (EDSS) score confirmed at 6 months, and classified per temporal association with relapses. Predictors of PIRA and RAW were assessed using multivariable Cox regression models.

Results:

PIRA occurred in 1472 (27.6%) and RAW in 240 (17.6%) patients. Predictors of PIRA were older age (HR=1.02;95%CI 1.02-1.03,p<0.001), RR course (HR=1.46;95%CI 1.30-1.64,p<0.001), longer disease duration (HR=1.49;95%CI 1.22-1.82,p<0.001), lower EDSS (HR=0.89;95%CI 0.85-0.93,p<0.001), lower number of relapses before the event (HR=0.93;95%CI 0.91-0.95,p<0.001). RAW was associated with younger age (HR=0.99;95%CI 0.98-0.99,p<0.001), RR course (HR=1.56; 95%CI 1.35-1.80,p<0.001), lower EDSS (HR=0.92;95%CI 0.87-0.97,p=0.002), higher number of relapses before the event (HR=1.07;95%CI 1.05-1.09,p<0.001). Longer exposure to disease modifying drugs (DMD) reduced the risk of both PIRA and RAW (p<0.001).

Conclusions:

in this early relapsing-onset MS cohort, PIRA was an important contributor to CDA. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum. The analysis on progression independent of relapse and radiological activity is ongoing.

Background and Aims:

Ocrelizumab (OCZ) has been approved in 2018 in Italy for the treatment of patients with multiple sclerosis (MS), but real-world data about its use are limited.

Aims: To evaluate effectiveness and safety of OCZ for primary progressive MS (PPMS), active secondary progressive (SPMS) and relapsing remitting MS (RRMS) patients recruited at the MS Center of Bari, Italy

Methods:

Patients with ≥3 infusions were retrospectively recruited. Clinical and demographic data were collected (Tab 1). Wilcoxon paired test was used to evaluate the EDSS changes over time. We assessed relapse incidence after treatment start and adverse events (AE).

Results:

Our cohort of 133 patients included 35 PPMS, 22 SPMS and 76 RRMS patients. The median (IQR) follow-up after the first DMT start were 2,09 (0,6-3,3), 1,8 (0.08-4.02), 1.63 (1.17-3.10) years for PPMS, RRMS and SPMS patients respectively. The last available EDSS after OCZ start significantly increased compared to the baseline values only in the PPMS group (p= 0.01), but it remained stable in SP and RR groups. No clinical relapses and no evidence of radiological activity were found in RRMS patients during follow up. AEs reported were mostly infusion-related reactions in all groups, 1 Dengue fever and 2 Herpes Zoster infections. Seven of our cases reported COVID-19 infection during pandemic, one of them died.

Conclusions:

Our real-world data indicate that OCZ stabilized disability progression and disease activity in RR and SP patients. The safety profile was quite favorable in this cohort.

Background and Aims:

To compare serum Neurofilament light chain (sNfL) levels in patients with Multiple Sclerosis (MS), MOG-Antibody Disease (MOGAD) and Neuromyelitis Optica Spectrum Disorders (NMOSD).

Methods:

We performed a propensity score (PS)-based nearest-neighbor matching within a caliper of 0.05 to select patients with homogeneous baseline characteristics. Using ultrasensitive single-molecule array assays (SIMOA), we measured sNfL in the sera of adult patients with MS (n=17), MOGAD (n=15), NMOSD with AQP4-Ab (n=16) and Healthy Controls (HCs) (n=24). MOG-IgG and AQP4-IgG were analysed by a semiquantitative ratiometric method. SNfL levels were compared among the different disease groups. Spearman test was used to evaluate the correlation between sNfL and EDSS score in each group and to estimate the correlation between MOG-IgG titer and sNFL levels.

Results:

MOGAD patients showed a significant lower sNFL levels compared to MS (median 16,47pg/mL range 5,10-71,78 vs 7,34 range 2,43-115,43; p=0.01) and NMOSD adult patients (median 16,46pg/mL range 4,2-196,47; p=0.02)[Fig.1]. All groups had an increased sNFL value compared to HCs (median 5,64pg/mL range 2,47-8,84; p<0.0001). A positive significant correlation was found between sNfL and EDSS scores in MOGAD (r=0.636; p=0.005), NMO-AQP4 (r=0.908; p<0.0001) and MS patients (r=0.534; p = 0.014) [Fig.2]. No correlation was found between MOG-IgG titers and sNfL levels (p=0.294).

Conclusions:

Our results confirm the value of sNfL as a clinically meaningful blood biomarker of disability levels in different demyelinating diseases. In MOGAD patients MOG-IgG titers are not correlated with the sNfL levels, suggesting that they are more related to inflammatory processes.

Background and Aims:

How aggressively and timely treat relapsing-remitting multiple sclerosis (RRMS) is still a matter of debate.

To evaluate long-term disability trajectories in RRMS patients treated with two different therapeutic 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 disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received, as first DMT natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine, mitoxantrone,. ESC group patients received the high efficacy DMT after ≥1 year of injectables DMTs, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS)-matched for characteristics at the first DMT. A longitudinal model for repeated measures was applied to evaluate the disability trajectories. To estimate the effect of early versus late start of high-efficacy DMT the mean annual EDSS changes were compared to baseline values (delta-EDSS) in EIT and ESC groups.

Results:

2,702 patients were included in our study cohort. After PS matching procedure 363 pairs were retained. The median (IQR) follow-up was 8.5 (6.5–11.7) years. The ESC strategy was associated with a faster EDSS increase over time in comparison to the EIT (p<0.02). The mean delta-EDSS differences between the two groups increased 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 findings indicate a higher effectiveness of EIT than ESC strategy in slowing disability worsening over time.