Sapienza University of Rome
Department of Human Neurosciences

Author Of 1 Presentation

Observational Studies Oral Presentation

PS01.04 - Comparison of disability trajectories in relapsing Multiple Sclerosis patients treated with early intensive or escalation treatment strategies

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.

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Author Of 2 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

P0354 - Management of infectious risk in multiple sclerosis: implication for screening, prophylaxis and therapies (ID 1839)

Speakers
Presentation Number
P0354
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

The DMTs largely used in MS may result in higher risk of infectious complications. Screening for and treatment of latent tuberculosis infection (LTBI) should be considered for patients receiving alemtuzumab, teriflunomide, fingolimod and natalizumab. Hepatitis B virus (HBV) reactivation may be harmful mainly for ocrelizumab and alemtuzumab treated patients.

Objectives

Aim of the study was to define the infectious risk in DMTs-treated MS patients with approaches tailored to individual patients.

Methods

At the Neuroinfectious Unit of Policlinico Umberto I (Rome), before starting or switching to DMTs, MS patients were evaluated for infectious risk. HBV and Mycobacterium tuberculosis (MTB) were investigated by serological test as hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), and by quantiFERON®-TB Gold In-Tube (QFT) assay, respectively. HBV-DNA detection was performed in chronic hepatitis B MS patients and monthly monitored during DMTs. In QFT positive patients, active tuberculosis (TB) was excluded by medical history and chest X-ray and when necessary, sputum smear microscopy, sputum culture and MTB PCR were also performed. All LTBI patients were undergone to TB prophylaxis (isoniazid+rifampicin) for 3 months. DMTs were started after one-month prophylaxis.

Results

One hundred thirty-eight MS patients (79 females, 59 males) with a median age [interquartile range (IQR)] of 47.5 (37-56), median years of disease (IQR) of 8 (2-18) and median EDSS (IQR) of 3.5 (2-6), were enrolled. Before starting DMTs, 10.1% (14/138) of patients had chronic B hepatitis and 10.1% (14/138) showed QFT positivity. During DMTs follow-up, one patient revealed HBV reactivation. The patient remained asymptomatic with liver enzymes unchanged. HBV-DNA became undetectable after 2 weeks of specific antiviral treatment without discontinuing ocrelizumab. Among QFT positive patients, no TB reactivation was observed. Interestingly, one of the QFT negative patients became positive during fingolimod treatment.

Conclusions

HBV and TB screening should be recommended in MS patients candidate for DMTs. HBV monitoring may avoid a fatal event and the choice of a preemptive strategy spares HBV prophylaxis when unnecessary. Beside preventing TB reactivation, TB prophylaxis based on two active molecules, allows an earlier starting of DMTs. Moreover, TB screening may contribute to reduce the transmission, morbidity, and mortality of active disease in global population.

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Epidemiology Poster Presentation

P0506 - Towards a validated Secondary Progressive Multiple Sclerosis definition: A study from the Italian MS Register (ID 1432)

Abstract

Background

No clear metrics for sensitive and reliable identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive (SP)MS are available.

Objectives

To compare diagnostic performances of two different data-driven Secondary Progressive Multiple Sclerosis definitions.

Methods

patient with RRMS with a follow-up ≥5 years, with a current age ≥18 years, and with ≥3 EDSS scores recorded were selected from the Italian MS Registry. Annual incidence of SPMS conversion was reported as number of patients converting to SP every 100 patients/year. Three different SPMS definitions have been used. Data-driven definitions based on the Lorscheider’s algorithm (LA) and on the EXPAND trial inclusion criteria were validated, using the neurologist’s definition as gold standard, in terms of calibration, discrimination and goodness of fit by calculating: sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), the Akaike information criterion (AIC), the Area Under the Curve (AUC). The overall calibration of the data-driven definitions was evaluated by the Calibration Slope test.

Results

a cohort of 10,240 RRMS patients was extracted from the Italian MS Registry. According to the neurologist judgment, 880 (8.59%) patients were classified as SPMS in the dataset. By applying the LA and the EXPAND definition, 1,806 (17.64%) and 1,134 (11.07%) patients, respectively, were classified as SPMS. The annual rate of SP conversion during the follow-up was 0.74 every 100 patients/year based on the neurologist’s definition, 1.57 every 100 patients/year using the LA and 0.94 every 100 patients/year applying the EXPAND definition. Both the data-driven definitions were well calibrated, with a p-value of the Calibration Slope test higher than 0.05 (LA=0.55; EXPAND definition=0.57). The AIC (LA=4301; EXPAND definition=5510) and the R-Square (LA=0.15 vs EXPAND definition=0.05), were in favor of the LA. The LA showed a greater discrimination power (AUC: 0.83 vs 0.65) and a higher sensitivity (77.1% vs 38.0%) in comparison to the EXPAND definition. Both definitions showed similar specificity (88.0% vs 91.5%). The PPV and the NPV were both higher using the LA than those obtained by the EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%, respectively).

Conclusions

An accurate definition of SP transition is needed for a timely and efficacious treatment of SPMS patients. Real-world data from the Italian MS Registry suggests that data-driven definitions had a greater ability to capture SP transition than neurologist’s definition and that the global accuracy of LA seems to be higher than a definition based on the EXPAND trial inclusion criteria.

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