Optimal responders to platform disease modifying therapies in an Italian cohort of relapsing-onset multiple sclerosis patients
SYNOPSIS AND RESULTS
Objectives: in a large cohort of multiple sclerosis (MS) patients with relapsing onset, the primary objective of the project is to identify the proportion of "optimal responders" to platform therapies and to compare their clinical characteristics at baseline with those of "poor responder" and patients who start highly effective therapies. The secondary objective of the project is to compare the risk of disability progression, achievement of EDSS 4, 6 and 7 and of conversion to the secondary progressive course (SP) in patients treated with the "escalating" approach compared to patients treated with "early aggressive" approach. Methods: inclusion criteria: confirmed diagnosis of CIS or RRMS according to McDonald's criteria 2010/2017; at least 3 clinical controls; treatment with moderate or high efficacy therapies; follow-up duration of at least 5 years. Therapies will be classified according to the two-layer classification: "moderate efficacy" (interferon; glatiramer acetate; teriflunomide; dimethyl fumarate; azathioprine) and "high efficacy" (fingolimod; natalizumab; anti-CD20; alemtuzumab; cyclophosphamide; mitoxantrone; cladribine) and three-layered: “high efficacy” (antiCD20, natalizumab, mitoxantrone and alemtuzumab), “moderate efficacy” (sphingosine 1 receptor modulators, cladribine, dimethyl fumarate), “modest efficacy” (teriflunomide, glatiramer acetate, interferons). The definition of “optimal responders” to platform therapies will include treatment with moderately effective therapies, absence of relapses, disability worsening and switch to highly effective therapies during follow-up. In the subgroup of patients in which the data will be available, the definition of "optimal responder" will also include the absence of brain and / or spinal MRI activity (appearance of new lesions and / or gadolinium-enhancing lesions). A definition of "optimal responder" will also be applied based only on the absence of disability worsening during the follow-up. On the whole, the aim of the project is to estimate the proportion of patients "optimal responder" to platform therapies, comparing their clinical characteristics at baseline with the group of "poor responder" patients and with that of patients treated with the "early aggressive" approach. This information will improve the initial prognostic classification of patients and approach to treatment decision-making. If the proportion of "optimal responders" to platform therapies in the long term was negligible, the opportunity to treat the vast majority of patients with an "early aggressive" approach should be considered, reserving platform therapies for situations of high infectious risk and de-escalation / de-risking.
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
Optimal responders to platform disease modifying therapies in an Italian cohort of relapsing-onset multiple sclerosis patients
Objectives: in a large cohort of multiple sclerosis (MS) patients with relapsing onset, the primary objective of the project is to identify the proportion of "optimal responders" to platform therapies and to compare their clinical characteristics at baseline with those of "poor responder" and patients who start highly effective therapies. The secondary objective of the project is to compare the risk of disability progression, achievement of EDSS 4, 6 and 7 and of conversion to the secondary progressive course (SP) in patients treated with the "escalating" approach compared to patients treated with "early aggressive" approach.
Methods: inclusion criteria: confirmed diagnosis of CIS or RRMS according to McDonald's criteria 2010/2017; at least 3 clinical controls; treatment with moderate or high efficacy therapies; follow-up duration of at least 5 years.
Therapies will be classified according to the two-layer classification: "moderate efficacy" (interferon; glatiramer acetate; teriflunomide; dimethyl fumarate; azathioprine) and "high efficacy" (fingolimod; natalizumab; anti-CD20; alemtuzumab; cyclophosphamide; mitoxantrone; cladribine) and three-layered: “high efficacy” (antiCD20, natalizumab, mitoxantrone and alemtuzumab), “moderate efficacy” (sphingosine 1 receptor modulators, cladribine, dimethyl fumarate), “modest efficacy” (teriflunomide, glatiramer acetate, interferons).
The definition of “optimal responders” to platform therapies will include treatment with moderately effective therapies, absence of relapses, disability worsening and switch to highly effective therapies during follow-up. In the subgroup of patients in which the data will be available, the definition of "optimal responder" will also include the absence of brain and / or spinal MRI activity (appearance of new lesions and / or gadolinium-enhancing lesions). A definition of "optimal responder" will also be applied based only on the absence of disability worsening during the follow-up.
On the whole, the aim of the project is to estimate the proportion of patients "optimal responder" to platform therapies, comparing their clinical characteristics at baseline with the group of "poor responder" patients and with that of patients treated with the "early aggressive" approach. This information will improve the initial prognostic classification of patients and approach to treatment decision-making. If the proportion of "optimal responders" to platform therapies in the long term was negligible, the opportunity to treat the vast majority of patients with an "early aggressive" approach should be considered, reserving platform therapies for situations of high infectious risk and de-escalation / de-risking.
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