Multiple Sclerosis Centre, Hospital of Gallarate, ASST della Valle Olona

Author Of 1 Presentation

Observational Studies Oral Presentation

PS05.03 - Disease modifying treatment may delay time to wheelchair in primary progressive multiple sclerosis: a real-life cohort

Abstract

Background

Background: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking, as randomized clinical trials failed to show efficacy in reducing disability progression in this patient population.

Objectives

Objective: To investigate the effectiveness of disease-modifying treatment (DMT) on hard disability outcomes (EDSS 6 and 7) in a real-life population of PPMS patients.

Methods

Methods: Using the Italian MS Registry, we selected PPMS patients with at least three EDSS evaluations and three years of follow-up. Study baseline was defined as the first EDSS evaluation for untreated patients and the date of the first DMT initiation for treated patients. The impact of DMT on the risk of reaching EDSS 6 and 7 was assessed as a dichotomous variable (yes versus no) and as a time-dependent covariate through multivariable Cox regression models (adjusted for age at baseline, sex, first EDSS score, symptoms at onset, annualized visit rate, annualized relapse rate). We compared outcomes with an as-treated analysis and used propensity-score matching (PSM) to select cohorts with comparable baseline characteristics. DMT-exposure was also evaluated in terms of quartiles of exposure.

Results

Results: Of the 1214 patients we included 671 females, mean ± Standard Deviation baseline age 48.7 ± 11.1 years, mean EDSS score 4.1 ± 1.8, 790 (65%) received a DMT during the follow-up (57% platform and 43% highly active treatments). In the whole sample, after a mean follow-up of 11.6 ± 6.3 years, 994 (82%) patients reached EDSS 6 and 539 (44%) EDSS 7. In the multivariable Cox regression models, the use of DMT analyzed as a dichotomous variable did not influence the risk of reaching EDSS 6 (aHR=1.1, 95% CI 0.95-1.28, p=0.181) and EDSS 7 (aHR = 0.93, 95% CI 0.77-1.12. p = 0.454). However, longer DMT exposure significantly reduced the risk of reaching EDSS 7 (aHR = 0.73, 95% CI 0.56-0.95, p =0.021). Of note, patients in the upper quartile of DMT exposure compared with those with shorter DMT exposure were younger at baseline (mean age 44.1 ± 10.6 years; p < 0.001) and received the first DMT closer to the disease onset (mean time to first DMT 6.8 years ± 6.1 ; p=0.002). All these findings were confirmed in the PSM analysis.

Conclusions

Conclusion: Our results suggest that longer exposure to DMT may delay time to wheelchair in PPMS patients. Moreover, treating younger patients and reducing the delay to treatment initiation may improve the patients’ long-term disability outcomes. To optimize treatment decision-making in PPMS further profiling of the best candidates to treatment is needed.

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Author Of 1 Presentation

Clinical Outcome Measures Poster Presentation

P0161 - Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: an Italian multicentric study. (ID 1603)

Speakers
Presentation Number
P0161
Presentation Topic
Clinical Outcome Measures

Abstract

Background

the management of MS patients (pts) who show disease activity after 2 alemtuzumab (ALM) courses represents an unsolved issue. No real-life data about the switch to ocrelizumab (OCR) have been reported yet.

Objectives

To describe efficacy and safety outcome of OCR patients switching from ALM due to persistence of disease activity after ALM

Methods

MS pts who switched from ALM to OCR from March 2019 to March 2020 were retro- and prospectively recruited from different Italian MS Centers. Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected.

Results

we recruited 23 MS pts [mean age: 35.7(SD±6.8); female, 40.1%; Relapsing Remitting, (RR): 75.8%, active Secondary progressive, (aSP): 24.2%; mean time interval (days) from II ALM course: 87.4(SD±108); cumulative number of relapses: 21; mean number of new T2 and Gd+ lesions: 4.1(SD±4.5) and 1.6(SD±3.1); median EDSS:3(range 1-7)]. The mean follow-up (FU) from OCR start was 7.9±7.4 months. Efficacy: 4 (17.4%) pts had a relapse after OCR start (1 pt relapsed between the first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start respectively), with complete recovery after steroid treatment. 4 (17.4%) pts showed radiological activity with no clinical correlates at 3 months (n=2), 4 months (n=1) and 9 months (n=1). EDSS was stable except for 1 aSP patient who showed 1-year disability progression. Safety: I) Infusion Associated Reactions (IARs) occurrence was significantly lower with respect to alemtuzumab courses (p<0.05); (ii) infections: mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). For 12 pts, data about immunophenotype were available. Of them, no pts showed T CD4+ cell count decrease <200 cell/mm3 at 3, 6-months and 1-year FU; complete B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU. 10 (43.4%) pts developed hypogammaglobulinemia without developing associated infectious events. C) Autoimmunity: no alemtuzumab-related new complications occurred.

Conclusions

short-term FU seems to suggest that the switch to OCR in MS patients who showed disease activity after 2 ALM courses is characterized by a good safety and efficacy profile, although clinical and neuroradiological activity can be detected both in an early and in a later phase of treatment. Longer follow-up is warranted and recruitment is still ongoing.

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