Table 2.
Main efficacy outcomes from real-world experience summarized according to the years of follow-up (up to 2 years, between the 3rd and 4th year, and beyond year 4).
| Follow-up period | Reference | Study type | Population | Main efficacy outcomes |
|---|---|---|---|---|
| Up to 2 years | Petracca et al. 68 | Multicentre, observational, retrospective post-marketing study | 243 patients (100% RRMS; 29.3% DMT-naïve) | - 64% NEDA-3: Higher number of prior treatments reduced NEDA-3 retention; clinical relapses were more likely. Median time to NEDA-3 loss: 2.6 years. - 89% relapse-free - 77% MRI activity-free - 87% disability progression-free |
| Sorensen et al. 57 | Prospective registry-based observational cohort study | 268 patients (97.8% RRMS; 12.7% DMT-naïve) | - 84.8% ARR reduction compared to the year before CLAD initiation. - NEDA-3 achieved: 71.7% at 1 year; 49.0% at 2 years. - Risk factors for relapse: Switching from HeDMT or high baseline disease activity. |
|
| Zanetta et al. 66 | Retrospective and prospective monocentric, observational study | 114 patients (100% RRMS; 50% DMT-naïve) | - 74.9% NEDA-3 at 24 months: Higher gadolinium-enhancing lesions at baseline predicted NEDA-3 loss - 90.9% relapse-free - 76.7% MRI activity-free - 96.2% disability progression-free |
|
| Arena et al. 144 (REWIND) | Prospective multicentre study | 217 patients (100% RRMS; 23% DMT-naïve) | - 80% EDSS progression-free - 88% relapse-free at 24 months - 48% MRI activity-free - NEDA-3 outcomes: Higher in the MAT group, with greater freedom from disease progression, clinical relapses and radiological worsening - ARR analysis: Lowest in MAT patients compared to naïve and HAT groups |
|
| Adamec et al. 58 | Retrospective observational multi-centre, multi-national study | 320 patients (100% RRMS; 26.6% DMT-naïve) | - 54.2% NEDA-3 - 72.5% MRI activity-free - 86.5% relapse-free - 90.2% disability progression-free |
|
| Al-Hashel et al. 65 | Observational, longitudinal prospective study | 72 patients (100% RRMS; 44.4% DMT-naïve) | - 75% NEDA-3 - 90% MRI activity-free - 85% relapse-free - 90% disability progression-free |
|
| Conway et al. 184 | Prospective multicentre study | 117 (64.2% RRMS; 9.4% SPMS; 1.9% PPMS; 13.2% PRMS; 11.3% CIS) | - Walking speed improvement over time (p < 0.001) with better scores compared to other DMTs - Stable patient determined disease steps and walking aid use - Stable MRI activity - 11% started a post-CladT DMT |
|
| Years 3–4 | Rauma et al. 69 | Non-interventional cohort study based on the Finnish MS registry | 179 (98.9% RRMS; 29.6% DMT-naïve) | - 86% relapse-free at last follow-up - 92.5% of DMT-naïve patients remained relapse-free until the end of follow-up - Mean ARR 0.1 during follow-up - 66.7% of patients with early relapse have switched from fingolimod |
| Magalashvili et al. 70 | Retrospective exploratory analysis from the Sheba MS Computerized Data Registry |
128 patients (80.5% RRMS; 14.8% SPMS; 4.7%CIS; 15.6% DMT-naïve) | - 59.0% NEDA-2 at Year 3 and 74.3% at Year 4 - 68.9% relapse-free patients at Year 3 and 82.9% at Year 4 - 83.6% EDSS stability or improvement at Year 3 and 85.7% at Year 4 |
|
| Aerts et al. 67 | Retrospective single centre study | 84 patients (100% RMS; 9.5% DMT-naïve) | - 72.5% NEDA-3 during observation period - 37 months median event-free survival - 72.6% remaining disease activity-free at the mean follow-up time (22.6 months) - 16.7% reported relapses - 93.3% MRI activity-free at 22.6 months - 83.3% and 66.7% relapse-free, 96.7% and 88.9% MRI activity-free, 82.8% and 77.8% CDW-free,72.4% and 55.6% disease activity-free at year 2 and 3, respectively - 88.3% SC lesion-free at 22.6 months |
|
| Schiavetti et al. 152 (CladSTOP) | Retrospective, multicentre, observational study | 204 PwMS (15.1% DMT-naïve) | - 91% ARR reduction at Month 36 - 28.0% EDSS improvement by ⩾0.5 points at Month 36 - 18.8% experienced disability progression at Month 36 - 70.4% no MRI activity or relapses |
|
| Manni et al. 47 | Prospective and retrospective single-centre, observational analysis of the Italian MS Registry | 88 patients (100% RMS; 20.5% DMT-naïve) | - 55.7% NEDA-3 at last follow-up - 75.0% NEDA-3 status retention and did not restart DMTs after >2 years post-last CladT dose - 90.9% relapse-free - 80.7% MRI activity-free - 70.4% disability progression-free |
|
| Beyond year 4 | Kowarik et al. 33 | Multicentre retrospective study | 187 patients (100% RMS; 21% DMT-naïve) | - 63% Monitored without therapy at Year 5 - 14% Treatment switch at Years 1–4 - 19% Continued CladT at Year 5 - 4% Therapy switch at Year 5 |
| Wallace et al. 153 | Observational multi-centre study | 116 patients (100% RRMS; 34.5% DMT-naïve) | - 89% ARR reduction at Year 5 - 75% Relapse-free patients at Year 5 - 83.6% No subsequent DMT up to 5 years post-CLAD initiation |
|
| Cañibano et al. 158 | Retrospective single-centre observational study | 46 (100% RMS; 48% DMT-naïve) | - ⩾88% ARR reduction at year 5 - Lower ARR in patients switching to cladribine from HeDMTs compared with platform therapies - 91% were free of relapses at year 5 - 100% MRI activity-free at year 5 - 80% NEDA-3 at year 5. |
ARR, annualized relapse rate; CDW, confirmed disability worsening; CIS, clinically isolated syndrome; CladT, cladribine tablets; DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; HeDMT, high efficacy disease-modifying therapy; MRI, magnetic resonance imaging; MS, multiple sclerosis; NEDA-3, no evidence of disease activity-3; PPMS, primary progressive multiple sclerosis; PRMS, progressive relapsing multiple sclerosis; PwMS, patients with multiple sclerosis; RMS, relapsing multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SC, spinal cord; SPMS, secondary progressive multiple sclerosis.