Table 3.
Studies on early HET vs. MET and early vs. delayed initiation HET
| Study | Design | Patients | HETs | Comparators | Outcomes |
|---|---|---|---|---|---|
| Early HET vs. early MET (with/without escalation) | |||||
| Labiano-Fontcuberta et al. (2022) [118] | Prospective longitudinal study | MS (N = 695) | Alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, rituximab | Cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, interferons, teriflunomide | Delay in starting HET was associated with cognitive worsening. MET was associated with higher risk of cognitive worsening vs. early HET |
| He et al. (2020) [119] | Observational cohort study | RRMS (N = 544) | Alemtuzumab, mitoxantrone, natalizumab, ocrelizumab, rituximab | Cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, teriflunomide | Early HET (< 2 years after disease onset) was associated with lower long-term disability and lower hazard of disability progression vs. late HET (4–6 years after disease onset) |
| Simonsen et al. (2021) [10] | Real-world cohort study | MS (N = 694) | Alemtuzumab, fingolimod, natalizumab | Dimethyl fumarate, glatiramer acetate, interferons, teriflunomide | Patients starting HET were more likely to achieve NEDA at 1 and 2 years vs. patients starting MET |
| Harding et al. (2019) [120] | Real-world cohort study | MS (N = 592) | Alemtuzumab, natalizumab | Dimethyl fumarate, fingolimod, glatiramer acetate, interferons, teriflunomide | Mean change in EDSS score at 5 years was lower with HET vs. MET |
| Buron et al. (2020) [121] | Observational cohort study | RRMS (N = 388) | Alemtuzumab, cladribine, daclizumab, fingolimod, natalizumab, ocrelizumab | Dimethyl fumarate, glatiramer acetate, interferon beta, teriflunomide | At 4 years: 47% lower rate of EDSS score worsening and 50% lower rate of first relapse with HET vs. MET |
| Brown et al. (2019) [122] | Observational cohort study | RRMS (N = 1555) | Alemtuzumab, fingolimod, natalizumab | Glatiramer acetate, interferon beta | Lower risk (HR, 0.66) of conversion to SPMS with HET vs. MET over a median of 5.8 years |
| Iaffaldano et al. (2021) [123] | Observational cohort study | RRMS (N = 2702) | Alemtuzumab, cladribine, fingolimod, natalizumab, ocrelizumab | Azathioprine, dimethyl fumarate, glatiramer acetate, interferon beta, teriflunomide | Change in EDSS score was lower with HET vs. MET for up to 10 years |
| Rojas et al. (2022) [124] | Retrospective cohort study | MS (N = 305) | Alemtuzumab, cladribine, mitoxantrone, natalizumab, ocrelizumab, rituximab | Dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, teriflunomide | HET decreased risk of EDSS score progression, relapses, and new MRI activity vs. MET |
| Early initiation HET vs. delayed initiation HET | |||||
| Labiano-Fontcuberta et al. (2022) [118] | Prospective longitudinal study | MS (N = 695) | Alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, rituximab | N/A | Each year of delay in starting HET was associated with cognitive worsening at 12 months (OR, 1.03) |
| Merkel et al. (2017) [125] | Systematic review | RRMS (12 studies) | Alemtuzumab, fingolimod, natalizumab | N/A | Early HET offers improved control of relapse activity vs. delayed HET |
EDSS Expanded Disability Status Scale, HET high-efficacy therapy, HR hazard ratio, MET moderate-efficacy therapy, MRI magnetic resonance imaging, MS multiple sclerosis, N/A not applicable, NEDA no evidence of disease activity, OR odds ratio, RRMS relapsing–remitting multiple sclerosis, SPMS secondary progressive multiple sclerosis