Author Of 1 Presentation
PS05.03 - Disease modifying treatment may delay time to wheelchair in primary progressive multiple sclerosis: a real-life cohort
- M. Fonderico
- E. Portaccio
- P. Iaffaldano
- L. Pastò
- L. Razzolini
- A. Bellinvia
- R. Fratangelo
- L. Tudisco
- G. De Luca
- P. Ragonese
- F. Patti
- V. Brescia Morra
- E. Cocco
- P. Sola
- M. Inglese
- G. Lus
- C. Pozzilli
- D. Maimone
- A. Lugaresi
- P. Gazzola
- G. Comi
- I. Pesci
- D. Spitaleri
- M. Rezzonico
- M. Vianello
- C. Avolio
- F. Logullo
- F. Granella
- M. Salvetti
- M. Zaffaroni
- C. Guaschino
- A. Ghezzi
- G. Lucisano
- M. Filippi
- M. Trojano
- M. Amato
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.
Author Of 1 Presentation
P0506 - Towards a validated Secondary Progressive Multiple Sclerosis definition: A study from the Italian MS Register (ID 1432)
- P. Iaffaldano
- G. Lucisano
- M. Filippi
- G. Comi
- M. Onofrj
- F. Patti
- V. Brescia Morra
- M. Zaffaroni
- C. Pozzilli
- E. Cocco
- P. Sola
- G. Salemi
- M. Inglese
- R. Bergamaschi
- S. Galgani
- M. Amato
- A. Conte
- M. Salvetti
- G. Lus
- C. Florio
- R. Totaro
- M. Vianello
- F. Granella
- E. Ferraro
- U. Aguglia
- M. Gatto
- B. Orlando
- F. Sangalli
- G. De Luca
- C. Chisari
- A. Carotenuto
- D. Baroncini
- D. Colombo
- M. Nica
- D. Paolicelli
- M. Trojano
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.