Early disease modifying treatment delays disability accumulation in patients with pediatric onset clinically isolated syndrome suggestive of multiple sclerosis
Author(s): ,
P Iaffaldano
Affiliations:
University of Bari Aldo Moro, Bari
,
M Simone
Affiliations:
University of Bari Aldo Moro, Bari
,
G Lucisano
Affiliations:
University of Bari Aldo Moro, Bari;Coresearch, Pescara
,
A Ghezzi
Affiliations:
Multiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate
,
G Coniglio
Affiliations:
Neurology Unit, “Madonna delle Grazie” Hospital, Matera
,
V Brescia Morra
Affiliations:
University 'Federico II', Naples
,
G Salemi
Affiliations:
University of Palermo, Palermo
,
F Patti
Affiliations:
University of Catania, Catania
,
A Lugaresi
Affiliations:
University 'G. D'Annunzio', Chieti;IRCCS Istituto delle Scienze Neurologiche - 'UOSI Riabilitazione Sclerosi Multipla', Bologna, Italy
,
G Izquierdo
Affiliations:
University of Bari Aldo Moro, Bari0
,
R Bergamaschi
Affiliations:
University of Bari Aldo Moro, BariUniversity of Bari Aldo Moro, Bari
,
J.A Cabrera-Gomez
Affiliations:
University of Bari Aldo Moro, BariCoresearch, Pescara
,
C Pozzilli
Affiliations:
University of Bari Aldo Moro, BariMultiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate
,
E Millefiorini
Affiliations:
University of Bari Aldo Moro, BariNeurology Unit, “Madonna delle Grazie” Hospital, Matera
,
R Alroughani
Affiliations:
University of Bari Aldo Moro, BariUniversity 'Federico II', Naples
,
C Boz
Affiliations:
University of Bari Aldo Moro, BariUniversity of Palermo, Palermo
,
E Pucci
Affiliations:
University of Bari Aldo Moro, BariUniversity of Catania, Catania
,
G.B Zimatore
Affiliations:
University of Bari Aldo Moro, BariUniversity 'G. D'Annunzio', Chieti
,
P Sola
Affiliations:
University of Bari Aldo Moro, BariIRCCS Istituto delle Scienze Neurologiche - 'UOSI Riabilitazione Sclerosi Multipla', Bologna, Italy
,
G Lus
Affiliations:
Coresearch, Pescara0
,
D Maimone
Affiliations:
Coresearch, PescaraUniversity of Bari Aldo Moro, Bari
,
C Avolio
Affiliations:
Coresearch, PescaraCoresearch, Pescara
,
E Cocco
Affiliations:
Coresearch, PescaraMultiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate
,
S.A Sajedi
Affiliations:
Coresearch, PescaraNeurology Unit, “Madonna delle Grazie” Hospital, Matera
,
G Costantino
Affiliations:
Coresearch, PescaraUniversity 'Federico II', Naples
,
P Duquette
Affiliations:
Coresearch, PescaraUniversity of Palermo, Palermo
,
V Shaygannejad
Affiliations:
Coresearch, PescaraUniversity of Catania, Catania
,
T Petersen
Affiliations:
Coresearch, PescaraUniversity 'G. D'Annunzio', Chieti
,
R Fernández Bolaños
Affiliations:
Coresearch, PescaraIRCCS Istituto delle Scienze Neurologiche - 'UOSI Riabilitazione Sclerosi Multipla', Bologna, Italy
,
D Paolicelli
Affiliations:
University of Bari Aldo Moro, Bari
,
C Tortorella
Affiliations:
University of Bari Aldo Moro, Bari
,
T Spelman
Affiliations:
Multiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate0;Multiple Sclerosis Center, S.Antonio Abate Hospital, GallarateUniversity of Bari Aldo Moro, Bari
,
L Margari
Affiliations:
University of Bari Aldo Moro, Bari
,
M.P Amato
Affiliations:
Multiple Sclerosis Center, S.Antonio Abate Hospital, GallarateCoresearch, Pescara
,
G Comi
Affiliations:
Multiple Sclerosis Center, S.Antonio Abate Hospital, GallarateMultiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate
,
H Butzkueven
Affiliations:
Multiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate0;Multiple Sclerosis Center, S.Antonio Abate Hospital, GallarateUniversity of Bari Aldo Moro, Bari
,
M Trojano
Affiliations:
University of Bari Aldo Moro, Bari
on behalf of Italian iMedWeb Registry, and MSBase Registry
on behalf of Italian iMedWeb Registry, and MSBase Registry
Affiliations:
ECTRIMS Online Library. Iaffaldano P. 09/16/16; 147034; 187
Pietro Iaffaldano
Pietro Iaffaldano
Contributions
Abstract

Abstract: 187

Type: Oral

Abstract Category: Clinical aspects of MS - Paediatric MS

Background: Identifying predictive factors of disability accumulation in children with clinically isolated syndrome suggestive (pCIS) of multiple sclerosis is still challenging to date.

Objectives: To assess prognostic indicators, including early disease modifying treatment (DMT) exposure, on disability progression in pCIS.

Methods: In a large cohort (n=770) of pCIS patients prospectively followed-up to 10 years

the RECursive Partitioning and AMalgamation (RECPAM) method was used to identify distinct subgroups of patients at different risk of reaching EDSS progression (a minimum 1-point increase in EDSS score above a baseline value, if the baseline EDSS was 1-5.5, or 1.5-point increase if the baseline EDSS was 0, and 0.5-point increase above baseline in the case of an EDSS score equal to or above 6). A backward Cox regression analysis with the RECPAM classes forced-in was carried out to highlight the role of DMT exposure and relapses before progression.

Results: RECPAM analysis identified 3 heterogeneous risk classes with different incidence of disability progression. Patients in the highest risk class (Class 1) had more frequently an age at onset greater than 12 years (97% vs 79% and 92%; p=0.002), an isolated spinal (33.3% vs 9.5% and 8.3% ; p=0.0003) or optic neuritis (30.3% vs 20.7% and 20.4%) symptom at onset, additional relapse/s after the first attack (39.4% vs 6.0% and 0%; p< 0.0001), and less frequently a DMT exposure (54% vs 78.5% and 71.3%; p=0.02) in comparison to patients belonging to the Classes 2 and 3. The backward Cox regression model with RECPAM classes forced-in, revealed the DMT exposure as the most important protective factor against the EDSS worsening (HR=0.22, 95% CI 0.13-0.38).

Conclusions: This work represents an important step forward in identifying predictors of an unfavorable course in patients with pCIS and, for the first time, it supports a beneficial effect of an early DMT exposure in preventing disability accumulation in this population.

Disclosure: Iaffaldano P. has served on scientific advisory boards for Biogen Idec, and has received funding for travel and/or speaker honoraria from Sanofi-Aventis, Biogen Idec, Teva and Novartis. Pozzilli C. has served on scientific advisory boards for Novartis, Merck Serono, Biogen Idec, Sanofi-Aventis Genzyme, Almiral and Bayer Schering and has received funding for travel and speaker honoraria from Sanofi-Aventis, Biogen Idec , Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, Genzyme, Actelion and Novartis, and receives research support from Novartis, Merck Serono, Biogen Idec, Bayer Schering and Sanofi-Aventis. Ghezzi A. has served on scientific advisory boards for Merck Serono, Biogen Idec, Novartis, Teva; received honoraria for speaking form Merck Serono, Biogen Idec, Genzyme, Almirall, and Novartis; received research support from Sanofi Genzyme, Biogen Idec and Merck Serono. Patti F. has undertaken advisory activities for Almirall, Bayer, Biogen Idec Italy, Merck Serono, Sanofi Genzyme and Novartis, he has received research support from FISM and MIUR; he has received personal compensation for speaking activities from Bayer, Biogen Idec Italy, Merck Serono, Novartis and TEVA; and travel grants from Bayer, Biogen Idec Italy, Merck Serono, Novartis and Sanofi Genzyme. Lugaresi A. was a Bayer Schering, Biogen Idec, Genzyme/Sanofi, Merck Serono, Novartis and Teva Advisory Board Member. She received travel grants and honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi and Teva and research grants from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi and Teva. She has also received travel and research grants from the Associazione Italiana Sclerosi Multipla and was a Consultant of “Fondazione Cesare Serono”.Amato M.P. received personal compensation from Merck Serono, Biogen, Bayer Schering, Genzyme, Teva and Novartis for serving on scientific advisory board and for speaking, received financial support for research activites from Merck Serono, Biogen Idec, Bayer Schering, Genzyme, Novartis, Genzyme and Teva.

Bergamaschi R. has served on scientific advisory boards for Biogen Idec and Almirall; has received funding for travel and speaker honoraria from Sanofi-Aventis, Genzyme, Biogen Idec , Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, and Novartis; received research support from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis, Almirall. Paolicelli D. received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Sanofi-Aventis, TEVA, Novartis, and Genzyme. Tortorella C. has served on scientific advisory boards for Biogen, Merck Serono, Bayer-Schering and Novartis. She received also funding for travel, consulting and speaker honoraria from Biogen, Merck Serono, Bayer-Schering, Teva, Genzyme, Novartis and Almirall. Sola P. received travel grants from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi and Teva. She received speaker honoraria from Bayer Schering, Sanofi-Genzyme, TEVA. Lus G. has served on scientific advisory boards for Almirall, Novartis, Biogen Idec, Sanofi-Aventis Genzyme, and Bayer Schering and has received funding for travel and speaker honoraria from Sanofi-Aventis, Biogen Idec, Bayer Schering, Teva Neurosciences, Almirall, Genzyme and Novartis, and receives research support from Novartis, "Fondazione C. Serono", Biogen Idec, Bayer Schering and Sanofi-Aventis. Comi G. has received consulting fees from Actelion, Bayer Schering, Merck Serono, Novartis, sanofi-aventis, Teva Pharmaceutical Ind. Ltd; lecture fees from Bayer Schering, Biogen Dompè, Merck Serono, Novartis, sanofi-aventis, Serono Symposia International Foundation, Teva Pharmaceutical. Trojano M. has received honoraria for consultancy or speaking from Biogen, Sanofi-Aventis, Merck Serono and Bayer-Schering and research grants from Merck Serono, Biogen and Novartis. Simone M, Coniglio G, Salemi G, Izquierdo G, Cabrera-Gomez JA, Alroughani R, Boz C, Pucci E, Zimatore GB, Maimone D, Avolio C, Aidin S, Costantino G, Duquette P, Shaygannejad V, Petersen T, Fernández Bolaños R, Spelman T, Margari L, Cocco E: have nothing to disclose.

Abstract: 187

Type: Oral

Abstract Category: Clinical aspects of MS - Paediatric MS

Background: Identifying predictive factors of disability accumulation in children with clinically isolated syndrome suggestive (pCIS) of multiple sclerosis is still challenging to date.

Objectives: To assess prognostic indicators, including early disease modifying treatment (DMT) exposure, on disability progression in pCIS.

Methods: In a large cohort (n=770) of pCIS patients prospectively followed-up to 10 years

the RECursive Partitioning and AMalgamation (RECPAM) method was used to identify distinct subgroups of patients at different risk of reaching EDSS progression (a minimum 1-point increase in EDSS score above a baseline value, if the baseline EDSS was 1-5.5, or 1.5-point increase if the baseline EDSS was 0, and 0.5-point increase above baseline in the case of an EDSS score equal to or above 6). A backward Cox regression analysis with the RECPAM classes forced-in was carried out to highlight the role of DMT exposure and relapses before progression.

Results: RECPAM analysis identified 3 heterogeneous risk classes with different incidence of disability progression. Patients in the highest risk class (Class 1) had more frequently an age at onset greater than 12 years (97% vs 79% and 92%; p=0.002), an isolated spinal (33.3% vs 9.5% and 8.3% ; p=0.0003) or optic neuritis (30.3% vs 20.7% and 20.4%) symptom at onset, additional relapse/s after the first attack (39.4% vs 6.0% and 0%; p< 0.0001), and less frequently a DMT exposure (54% vs 78.5% and 71.3%; p=0.02) in comparison to patients belonging to the Classes 2 and 3. The backward Cox regression model with RECPAM classes forced-in, revealed the DMT exposure as the most important protective factor against the EDSS worsening (HR=0.22, 95% CI 0.13-0.38).

Conclusions: This work represents an important step forward in identifying predictors of an unfavorable course in patients with pCIS and, for the first time, it supports a beneficial effect of an early DMT exposure in preventing disability accumulation in this population.

Disclosure: Iaffaldano P. has served on scientific advisory boards for Biogen Idec, and has received funding for travel and/or speaker honoraria from Sanofi-Aventis, Biogen Idec, Teva and Novartis. Pozzilli C. has served on scientific advisory boards for Novartis, Merck Serono, Biogen Idec, Sanofi-Aventis Genzyme, Almiral and Bayer Schering and has received funding for travel and speaker honoraria from Sanofi-Aventis, Biogen Idec , Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, Genzyme, Actelion and Novartis, and receives research support from Novartis, Merck Serono, Biogen Idec, Bayer Schering and Sanofi-Aventis. Ghezzi A. has served on scientific advisory boards for Merck Serono, Biogen Idec, Novartis, Teva; received honoraria for speaking form Merck Serono, Biogen Idec, Genzyme, Almirall, and Novartis; received research support from Sanofi Genzyme, Biogen Idec and Merck Serono. Patti F. has undertaken advisory activities for Almirall, Bayer, Biogen Idec Italy, Merck Serono, Sanofi Genzyme and Novartis, he has received research support from FISM and MIUR; he has received personal compensation for speaking activities from Bayer, Biogen Idec Italy, Merck Serono, Novartis and TEVA; and travel grants from Bayer, Biogen Idec Italy, Merck Serono, Novartis and Sanofi Genzyme. Lugaresi A. was a Bayer Schering, Biogen Idec, Genzyme/Sanofi, Merck Serono, Novartis and Teva Advisory Board Member. She received travel grants and honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi and Teva and research grants from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi and Teva. She has also received travel and research grants from the Associazione Italiana Sclerosi Multipla and was a Consultant of “Fondazione Cesare Serono”.Amato M.P. received personal compensation from Merck Serono, Biogen, Bayer Schering, Genzyme, Teva and Novartis for serving on scientific advisory board and for speaking, received financial support for research activites from Merck Serono, Biogen Idec, Bayer Schering, Genzyme, Novartis, Genzyme and Teva.

Bergamaschi R. has served on scientific advisory boards for Biogen Idec and Almirall; has received funding for travel and speaker honoraria from Sanofi-Aventis, Genzyme, Biogen Idec , Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, and Novartis; received research support from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis, Almirall. Paolicelli D. received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Sanofi-Aventis, TEVA, Novartis, and Genzyme. Tortorella C. has served on scientific advisory boards for Biogen, Merck Serono, Bayer-Schering and Novartis. She received also funding for travel, consulting and speaker honoraria from Biogen, Merck Serono, Bayer-Schering, Teva, Genzyme, Novartis and Almirall. Sola P. received travel grants from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi and Teva. She received speaker honoraria from Bayer Schering, Sanofi-Genzyme, TEVA. Lus G. has served on scientific advisory boards for Almirall, Novartis, Biogen Idec, Sanofi-Aventis Genzyme, and Bayer Schering and has received funding for travel and speaker honoraria from Sanofi-Aventis, Biogen Idec, Bayer Schering, Teva Neurosciences, Almirall, Genzyme and Novartis, and receives research support from Novartis, "Fondazione C. Serono", Biogen Idec, Bayer Schering and Sanofi-Aventis. Comi G. has received consulting fees from Actelion, Bayer Schering, Merck Serono, Novartis, sanofi-aventis, Teva Pharmaceutical Ind. Ltd; lecture fees from Bayer Schering, Biogen Dompè, Merck Serono, Novartis, sanofi-aventis, Serono Symposia International Foundation, Teva Pharmaceutical. Trojano M. has received honoraria for consultancy or speaking from Biogen, Sanofi-Aventis, Merck Serono and Bayer-Schering and research grants from Merck Serono, Biogen and Novartis. Simone M, Coniglio G, Salemi G, Izquierdo G, Cabrera-Gomez JA, Alroughani R, Boz C, Pucci E, Zimatore GB, Maimone D, Avolio C, Aidin S, Costantino G, Duquette P, Shaygannejad V, Petersen T, Fernández Bolaños R, Spelman T, Margari L, Cocco E: have nothing to disclose.

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