Table 2.
RCT with data on DMT efficacy in active SPMS or RMS including SPMS patients.
| DMT | EU-Label for active SPMS / RMS | US Label for active SPMS / RMS | Clinical trial with data on SPMS/RMS, initial publication year | Comparator | Study population | SPMS-specific
population, n (%) |
Data for SPMS available | Primary endpoint met |
|---|---|---|---|---|---|---|---|---|
| Cladribine | Highly active RMS | RMS | CLARITY 201013,53 | Placebo | RRMS, N = 1,326 | 374 (28.2)a | No | Yes |
| ONWARD 201813,54
(add-on to IFN-beta) |
Placebo | RMS, N = 197b | 26 (13.2) SPMS with relapses | From post hoc subgroup analysis | Yes | |||
| IFN-beta 1a i.m. | None | RMS | IMPACT 200216 | Placebo | SPMS, N = 436 | 436 (100) | Yes | No |
| IFN-beta 1a s.c. | RMS | RMS | SPECTRIMS 200121,55 | Placebo | SPMS, N = 618 | 618 (100) | Yes | No |
| Nordic Study 200456 | Placebo | SPMS, N = 371 | 371 (100) | Yes | No | |||
| IFN-beta 1b s.c. | SPMS with relapses | RMS | European Study Group 199857–59 | Placebo | SPMS, N = 718 | 718 (100) | Yes | Yes |
| North American Study Group 200458,60 | Placebo | SPMS, N = 939 | 939 (100) | Yes | No | |||
| Mitoxantrone | Highly active RMS | SPMS | MIMS 200251 | Placebo | SPMS / progressive RRMS, N = 188c | 94 (50.0) | No | Yes |
| Natalizumab | None | RMS | ASCEND 201817 | Placebo | SPMS, N = 889 | 889 (100) | Yes | No |
| Ocrelizumab | Active RMS | RMS | OPERA I/II 20179,11,61 | IFN-beta 1a | RMS, N = 1,656 | 1.9% to 10.2% | From post hoc subgroup analysis | Yes |
| Ofatumumab | Active RMS | RMS | ASCLEPIOS I/II 202012,62 | Teriflunomide | RMS, N = 1,882 | 108 (5.7) active SPMS | From post hoc subgroup analysis | Yes |
| Ponesimod | Active RMS | RMS | OPTIMUM 202115,63 | Teriflunomide | RMS, N = 1,133 | 29 (2.6) SPMS with relapses | From post hoc subgroup analysis | Yes |
| Siponimod | Active SPMS | RMS | EXPAND 201864 | Placebo | SPMS, N = 1,651 | 1.651 (100) | Yes | Yes |
| Teriflunomide | None | RMS | TOWER 201465 | Placebo | RMS, N = 1,169 | 9 (0.8) | No | Yes |
| TEMSO 201166 | Placebo | RMS, N = 1,088 | 51 (4.7) | No | Yes | |||
| TENERE 201467 | IFN-beta 1a | RMS, N = 324 | 1 (0.3) | No | No |
IFN, interferon; i.m., intramuscular; N, number of randomized patients; RMS, relapsing multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; s.c., subcutaneous; SPMS, secondary progressive multiple sclerosis.
A total of 374 (28%) had a baseline EDSS of 4 or higher, indicating that a proportion of patients may have transitioned to SPMS.
The original protocol included two doses of cladribine (3.5 mg/kg and 5.25 mg/kg). By protocol amendment, the higher dose of cladribine was omitted. In total, 197 patients were included in the placebo and cladribine 3.5 mg/kg groups of the original (N = 25) and the amended protocol (N = 172).
A total of 194 patients were randomized. Of these, 188 received treatment and had at least one efficacy assessment. These patients were included in the analysis. MS subtype is available for the analysis population only.