Retrospective pilot study on long-term Cladribine effects in patients with relapsing remitting multiple sclerosis or clinically isolated syndrome.
SYNOPSIS AND RESULTS
The aim of this Italian pilot study call CLARINET-MS study is to explore the feasibility of the retrospective approach for evaluating effectiveness in subjects previously treated with Cladribine and then followed as per clinical practice. The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLEMS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model.
Data start
Data end
2017-10-20
2020-06-15
PARTICIPATING CENTERS
Maria Pia Amato, Dipartimento NEUROFARBA, Divisione di Riabilitazione Neurologica, Azienda Ospedaliero-Universitaria Careggi; IRCCS Fondazione Don Carlo Gnocchi, Firenze Eleonora Cocco, Centro Regionale per la diagnosi e la cura della Sclerosi Multipla ASL8, Università degli Studi di Cagliari, Cagliari Maura Chiara Danni Centro Sclerosi Multipla, Clinica Neurologica, Ospedali Riuniti, Ancona Massimo Filippi, Dipartimento di Neurologia e Neurofisiologia, Centro SM, Neuroimaging Research Unit, Istituto Scientifico San Raffaele, Milano Claudio Gasperini, Centro Sclerosi Multipla, Azienda Ospedale S. Camillo Forlanini, Roma Matilde Inglese, Dipartimento di Neuroscienze, Riabilitazione Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Ospedale Policlinico San Martino-IRCCS, Genova Giovanna De Luca, Clinica Neurologica, Università G. D’Annunzio, Ospedale clinicizzato SS. Annunziata, Chieti Giacomo Lus, Centro SM, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Napoli Giulia Mallucci, IRCCS Fondazione Mondino, Pavia Girolama Alessandra Marfia, Centro di Riferimento Regionale per la SM Policlinico Tor Vergata, Roma Francesco Patti, Centro SM, Azienda Ospedaliera-Universitaria, Policlinico Vittorio Emanuele, Università degli Studi di Catania, Catania Ilaria Pesci, Centro SM, UO Neurologia, Ospedale Fidenza, Fidenza Martina Petruzzo, Centro Regionale SM, Unità Operativa Semplice, AOU Policlinico Federico II, Napoli Carlo Pozzilli Centro SM, Ospedale S. Andrea, Sapienza Università di Roma, Roma Giovacchino Tedeschi I Clinica Neurologica, Dipartimento di Scienze Mediche e Chirurgiche Avanzate, Università della Campania “Luigi Vanvitelli”, Napoli Maria Trojano, Centro SM, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso Università di Bari, Bari Mauro Zaffaroni, Centro SM ASST della Valle Olona, Ospedale di Gallarate, Gallarete, (VA)
OUTCOME
Introduction and aims The aim of this Italian pilot study call CLARINET-MS study is to explore the feasibility of the retrospective approach for evaluating effectiveness in subjects previously treated with Cladribine and then followed as per clinical practice. The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLEMS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model.
Results Time span under observation in the Italian MS Registry was 1–137 (median 80.3) months. In the total Italian patient population (n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5–39.5) months.
Conclusions CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2, and in some patients with RRMS and relapsing SPMS up to 60 months after the last dose.
Pubblicazioni e Comunicazioni a Congressi/ Publications and Congress Presentations Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS). Ther Adv Neurol Disord. 2020 Jun 10;13:1756286420922685. doi: 10.1177/1756286420922685. eCollection 2020
PUBLICATIONS
Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS). Ther Adv Neurol Disord. 2020 Jun 10;13.
Fondazione Italiana Sclerosi Multipla – FISM – Ente del Terzo Settore/ETS e, in forma abbreviata, FISM ETS. Iscrizione al RUNTS Rep. N° 89695 - Fondazione con Riconoscimento di Personalità Giuridica - C.F. 95051730109
Retrospective pilot study on long-term Cladribine effects in patients with relapsing remitting multiple sclerosis or clinically isolated syndrome.
The aim of this Italian pilot study call CLARINET-MS study is to explore the feasibility of the retrospective approach for evaluating effectiveness in subjects previously treated with Cladribine and then followed as per clinical practice.
The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLEMS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model.
Maria Pia Amato, Dipartimento NEUROFARBA, Divisione di Riabilitazione Neurologica, Azienda Ospedaliero-Universitaria Careggi; IRCCS Fondazione Don Carlo Gnocchi, Firenze
Eleonora Cocco, Centro Regionale per la diagnosi e la cura della Sclerosi Multipla ASL8, Università degli Studi di Cagliari, Cagliari
Maura Chiara Danni Centro Sclerosi Multipla, Clinica Neurologica, Ospedali Riuniti, Ancona
Massimo Filippi, Dipartimento di Neurologia e Neurofisiologia, Centro SM, Neuroimaging Research Unit, Istituto Scientifico San Raffaele, Milano
Claudio Gasperini, Centro Sclerosi Multipla, Azienda Ospedale S. Camillo Forlanini, Roma
Matilde Inglese, Dipartimento di Neuroscienze, Riabilitazione Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Ospedale Policlinico San Martino-IRCCS, Genova
Giovanna De Luca, Clinica Neurologica, Università G. D’Annunzio, Ospedale clinicizzato SS. Annunziata, Chieti
Giacomo Lus, Centro SM, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Napoli
Giulia Mallucci, IRCCS Fondazione Mondino, Pavia
Girolama Alessandra Marfia, Centro di Riferimento Regionale per la SM Policlinico Tor Vergata, Roma
Francesco Patti, Centro SM, Azienda Ospedaliera-Universitaria, Policlinico Vittorio Emanuele, Università degli Studi di Catania, Catania
Ilaria Pesci, Centro SM, UO Neurologia, Ospedale Fidenza, Fidenza
Martina Petruzzo, Centro Regionale SM, Unità Operativa Semplice, AOU Policlinico Federico II, Napoli
Carlo Pozzilli Centro SM, Ospedale S. Andrea, Sapienza Università di Roma, Roma
Giovacchino Tedeschi I Clinica Neurologica, Dipartimento di Scienze Mediche e Chirurgiche Avanzate, Università della Campania “Luigi Vanvitelli”, Napoli
Maria Trojano, Centro SM, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso Università di Bari, Bari
Mauro Zaffaroni, Centro SM ASST della Valle Olona, Ospedale di Gallarate, Gallarete, (VA)
Introduction and aims
The aim of this Italian pilot study call CLARINET-MS study is to explore the feasibility of the retrospective approach for evaluating effectiveness in subjects previously treated with Cladribine and then followed as per clinical practice.
The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLEMS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan–Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model.
Results
Time span under observation in the Italian MS Registry was 1–137 (median 80.3) months. In the total Italian patient population (n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5–39.5) months.
Conclusions
CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2, and in some patients with RRMS and relapsing SPMS up to 60 months after the last dose.
Pubblicazioni e Comunicazioni a Congressi/ Publications and Congress Presentations
Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS).
Ther Adv Neurol Disord. 2020 Jun 10;13:1756286420922685. doi: 10.1177/1756286420922685. eCollection 2020
Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS).
Ther Adv Neurol Disord. 2020 Jun 10;13.
https://doi.org/10.1177/1756286420922685
https://pubmed.ncbi.nlm.nih.gov/32587633/