Table 3.
Clinical trials in progressive MS. Adapted from Ciotti JR and Cross AH (79).
| Tested drug | Type of MS | Number of subjects | Duration | Primary endpoint | Results |
|---|---|---|---|---|---|
| MECHANISM OF ACTION: NON-SELECTIVE IMMUNOSUPPRESSANTS | |||||
| Cyclophosphamide 750 mg/m2 vs. IV glucocorticoids | SPMS | 138 | 2 years | Time to progression (using EDSS) | Failure |
| Sulfasalazine 500–2,000 mg daily vs. placebo | RRMS, SPMS, PPMS | 199 | 3 years | Time to progression (using EDSS) | Failure |
| Mitoxantrone 5 or 12 mg/ m2 q3 months vs. placebo | PRMS, SPMS | 194 | 1.5 years | Sequentially tested endpoints were change in EDSS, changes in ambulation, relapses, time to first relapse, and changes in SNS | p < 0.0001 |
| Cladribine 0.7 or 2.1 mg/kg (total dose over course) vs. placebo | SPMS, PPMS | 159 | 1 year | Mean change in EDSS | Failure |
| MECHANISM OF ACTION: IMMUNOMODULATORS | |||||
| IFN beta 1-b 8 million IU every other day vs. placebo (European trial) | SPMS | 718 | 1,5 years | Confirmed progression of disability measured by EDSS | p = 0.007 |
| IFN beta 1-b 250 or 160 mcg every other day vs. placebo (American trial) | SPMS | 939 | 3 years | Confirmed progression of disability measured by EDSS | Failure |
| IFN beta 1-a 22 mcg, 44 mcg vs. placebo (SPECTRIMS) | SPMS | 618 | 3 years | Confirmed progression of disability measured by EDSS | Failure |
| IFN beta 1-b 8 MUI every other day vs. placebo | PPMS, SPMS | 73 | 2 years | EDSS | Failure |
| IFN beta 1-a 60 mcg q Weekly vs. placebo (IMPACT) | SPMS | 436 | 2 years | MSFC | p = 0.003 |
| Glatiramer acetate 20 mg daily vs. placebo | PPMS | 943 | 3 years | Time to EDSS worsening | Failure |
| Laquinimod 0.6 mg daily vs. placebo | PPMS | 374 | 1 year | Percentage of change in brain volume | Failure |
| MONOCLONAL ANTIBODY | |||||
| Rituximab 1,000 mg q6 months vs. placebo | PPMS | 439 | 2 years | Time to EDSS worsening | Failure |
| Natalizumab 300 mg IV q4 weeks vs. placebo | SPMS | 889 | 2 years | Percentage of patients with progression in EDSS, T25FW or 9HPT | Failure |
| Ocrelizumab 600 mg q6 months vs. placebo | PPMS | 732 | 3 years | Percentage of patients with progression in EDSS | p = 0.03 |
| Opicinumab 3 or 10 or 30 or 100 mg/kg every 4 weeks + IFN beta 1-a vs. placebo +IFN beta 1a | RRMS, active SPMS | 418 | 1.5 years | Percentage of patients with improvements in EDSS, T25FW, 9HPT o PASAT | Failure |
| MECHANISM OF ACTION: SELECTIVE IMMUNOSUPPRESSANTS | |||||
| Siponimod 0.25-2 mg vs. placebo | SPMS | 1651 | 3 years | Confirmed progression of disability measured by EDSS | p = 0.013 |
| Fingolimod 0.5 mg or 1.25 mg daily vs. placebo | PPMS | 970 | 5 years | Time to progression measured by EDSS, T25FW, or 9HPT | Failure |
| MECHANISM OF ACTION: NEUROPROTECTOR | |||||
| Ibudilast 100 mg daily vs. placebo (added to patient's immunomodulator treatment) | SPMS, PPMS | 255 | 2 years | Change in brain volume assessed by BPF | p = 0.04 |
| Biotin 300 mg daily vs. placebo (added to patient's immunomodulator treatment) | SPMS, PPMS | 154 | 1 year | Proportion of disability improvement (EDSS and T25FW) | p = 0.005 |
9HPT, Nine-hole peg test; BPF, Brain parenchymal fraction; EDSS, expanded disability Status score; IU, international units; MSFC, Multiple sclerosis functional composite; PPMS, primary progressive multiple sclerosis; PRMS, progressive relapsing multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SNS, standardized neurological status; SPMS, secondary progressive multiple sclerosis; T25FW, timed 25-foot walk.