A multicentric randomized PRAGmatic trial to compare the effectiveness of fingolimod versus dimethyl-fumarate on patient overall disease experience in relapsing remitting Multiple Sclerosis:

INTERVENTION: Trade Name: GILENYA ‐ 0.5 MG ‐ CAPSULE RIGIDE ‐ USO ORALE ‐ BLISTER DIVISIBILE PER DOSE UNITARIA(PVC/PVDC/ALU) SCATOLA DA 7X1 CAPSULE Pharmaceutical Form: Capsule, hard INN or Proposed INN: FINGOLIMOD CAS Number: 162359‐55‐9 Current Sponsor code: FINGOLIMOD Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0‐ Trade Name: TECFIDERA ‐ 240 MG ‐ CAPSULA RIGIDA GASTRORESISTENTE ‐ USO ORALE ‐ BLISTER (PVC/PE/PVDC‐PVC ALLUMINIO) ‐ 56 CAPSULE Pharmaceutical Form: Gastro‐resistant capsule, hard INN or Proposed INN: DIMETIL‐FUMARATO CAS Number: 624‐49‐7 Current Sponsor code: DIMETIL Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 240‐ CONDITION: relapsing‐remitting multiple sclerosis ; MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing‐remitting multiple sclerosis System Organ Class: 10029205 ‐ Nervous system disorders ; MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 ‐ Nervous system disorders ; MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing‐remitting multiple sclerosis System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To compare the effectiveness of fingolimod 0.5 mg once daily versus dimethyl‐fumarate 240 mg twice daily in their ability to maintain the NEDA status over 24 months in RRMS patients.; The NEDA status is satisfied when all the three following criteria are fullfilled:; 1. no clinical relapse; 2. no new or enlarged T2 lesions or T1 gadolinium‐enhanced lesions at the MRI; 3. no neurological progression of the clinical status evaluated by means of EDSS Primary end point(s): The time for losing the NEDA status Secondary Objective: to compare the effectiveness of the two oral Disease Modifying Treatments (DMTs) in terms of; 1. prevention of clinical relapses over 12 and 24 months ; 2. prevention of MRI activity over 12 and 24 months ; 3. prevention of brain atrophy over 12 and 24 months; 4. prevention of sustained disability progression (EDSS worsening) over 24 months¿; 5. prevention of perceived sustained disability progression (patient‐reported disability worsening) over 24 months¿; 6. prevention of objective sustained disability progression assessed by inertial sensors over 12 and 24 months¿; 7. patient‐NEDA (no patient‐reported EDSS worsening, no clinical relapse, no MRI activity, preservation of quality of life) over 24 months; 8. prevention of cognitive decline over 12 and 24 months¿; 9. preservation of quality of life over 12 and 24 months; 10. convenience perception over 12 and 24 month¿; 11. psychiatric symptoms and fatigue over 12 and 24 months ; Timepoint(s) of evaluation of this end point: 12 and 24 months INCLUSION CRITERIA: adult patients diagnosed with relapsing remitting multiple sclerosis who are eligible to both fingolimod and dimethyl‐fumarate treatment as for local authority indications and clinical judgement could be enrolled in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 900 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100 SECONDARY OUTCOME: Secondary end point(s): Annual relapse rate; Number of Gd+ MRI Lesion; Brain volume loss; Percentage of patients with confirmed increase of 1 point on PDDSS; Percentage of patients with a confirmed increase of 1 point on the EDSS scale; Change in gait performance assessed by inertial sensors; Percentage of patients maintaining patients‐NEDA status; 8. Change in cognitive impairment index (CII) assessed by Brief Repeatable Battery of Neuropsychological tests (BRB‐N), in social cognition assessed by Story based Empathy task (SET), and in quality of decision making assessed by Game of Dice Task (GDT) ; 9. Change in health related Qol assessed by EuroQOL‐5D (EQ‐5D) and The Multiple Sclerosis Quality‐of‐Life‐54 (MSQOL‐54) and in individualized Qol assessed by The SEIQoL‐DW ; Convenience perception as measured by the convenience scale within TSQM‐9 ; Symptomatic changes as determinated by Modified Fatigue Impact Scale (MFIS) and Hospital Anxiety & Depression Scale (HADS) Timepoint(s) of evaluation of this end point: over 12 and 24 months; at 12 and 24 months; at 12 and 24 months; over 24 months; over 24 months; over 12 and 24 months; over 24 months; at 12 and 24 months; over 12 and 24 months; over 12 and 24 months; over 24 months