Table 3.
Comparative Analysis of Multiple Sclerosis Studies Potentially Addressing Headache in IFN-β Receivers
| Study | Type of IFN-β | No of Patients on IFN-ß | Study Duration | Study Design and IFN-ß Type | Headache Frequency |
|---|---|---|---|---|---|
| OWIMS 199912 | SC-IFNβ-1a 22 µg QW | 95 | 48 weeks | Randomized, double-blind study of IFN-ß-1a 22 µg, 44 µg, or placebo administered once weekly SC injection. | 46 (48%) |
| SC-IFNβ-1a 44 µg QW | 98 | 48 weeks | 49 (50%) | ||
| EVIDENCE 200223 | IFN-β-1a 44 µg SC t.i.w | 339 | 24 weeks | Randomized trial compared IFN-ß −1a 44 ug SC t.i.w, and IFN-ß −1a 30 µg IM QW | 143 (42%) |
| IFN-β-1a 30 µg QW | 337 | 165 (49%) | |||
| Herndon et al25 | IM IFN-β-1a QW | 279 | 8 years | Open-label extension study of the phase III trial of IM IFN- ß −1a | 58% |
| BENEFIT26 | 250 μg IFN-ß-1b | 292 | 24 months | Randomized, double-blind trial of IFN-ß-1b 250ug SC EOD vs placebo | 78 (26.7%) |
| REGARD27 | IFN-β-1a 44 µg SC t.i.w | 381 | 96 weeks | Open label, randomized trial of 44 ug SC t.i.w IFN-ß-1a vs daily SC 20 mg GA. | 74 (19.4%) |
| BEYOND28 | 500 μg IFN- β-1b | 887 | Filling of the triangle design (2–3.5 years) | Randomized trial assigned 2:2:1 to receive one of two doses of IFN- ß −1b (250 μg or 500 μg) SC, EOD vs daily SC 20 mg GA | 293 (33%) |
| 250 μg IFN-β-1b | 888 | 280 (32%) | |||
| RNF24 | IFN-β-1a (RNF) 44 µg SC t.i.w | 260 | 96 weeks | Single-arm, Phase IIIb, open-label study to evaluate RNF, 44 μg SC t.i.w. | 98 (37.7%) |
| 16-year LTF29 | IFN-β-1b | 69 (within past 2 years) | LTF visit (Past 2 years) | Multi-center, observational study through a structured questionnaire | 19 (27.5%) |
| ADVANCE30 | Peginterferon ß −1a 125 μg every 2 weeks | 512 | 2 years | Randomized, double-blind, placebo-controlled, phase III study to to receive placebo or SC peg-IFN-ß-1a 125 μg every 2 weeks or every 4 weeks | 224 (44%) |
| Peginterferon ß-1a 125 μg every 4 weeks | 500 | 204 (41%) | |||
| Smith et al21 | IFN-β-1a 44 µg SC t.i.w | 8,107 | 6 years (eligible subjects) | Observational, retrospective Post-marketing study of IFN-β-1a SC tiw | IRs/100 person-years 6.94 (6.52–7.38) |
| REFLEXION31 | SC IFN-β-1a tiw | 99 | 60 months | Extension trial of the phase III REFLEX study32 | 16(16.2%) |
| SC IFN-β-1a QW | 117 | 19(16.2%) | |||
| Delayed treatment | 84 | 11(13.1%) |
Abbreviations: ADVANCE, pegylated interferon ß-1a for relapsing-remitting multiple sclerosis; BENEFIT, Betaferon®/Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment; BEYOND, Betaferon®/Betaseron® Efficacy Yielding Outcomes of a New Dose; EOD, every other day; EVIDENCE, Evidence of Interferon Dose-Response: European North American Comparative Efficacy; GA, Glatiramer acetate; IM, intramuscular; IFN-β, interferon-beta; IM, intramuscular; IRs, incidence rates; LTF, long term follow-up; OWIMS, The Once Weekly Interferon for MS Study Group; QW, once a week; REFLEX, REbif FLEXible dosing in early MS; REFLEXION, REbif FLEXible dosing in early MS extension; REGARD, the REbif vs Glatiramer Acetate in Relapsing MS Disease; RNF, Rebif ®New Formulation; SC, subcutaneous; t.i.w, three times a week.