In a multicenter RCT «Lublin F, Miller DH, Freedman MS, ym. Oral fingoli...»1, there was no difference between fingolimod and placebo, when measured with 25'TWT and 9-HPT scores (data not shown). However, fingolimod reduced the number of new or newly enlarging T2 lesions by 73% (rate ratio 0·267, 95% CI 0·185–0·386; p<0·0001), of Gd-enhancing T1 lesions by 78% (0·217, 0·102–0·463; p<0·0001), and of new T1 hypointense lesions by 62% (0·375, 0·240–0·587; p<0·0001).
The incidence of adverse events in the efficacy analysis set was generally similar between groups. Adverse events were mild or moderate in severity in 249 (74%) of 336 receiving fingolimod and 366 (75%) of 487 receiving placebo. However, the reason to discontinue the study was adverse event in 15 % of patients in fingolimod group vs. 7 % of patients in placebo group.
| Ref. | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial | |||||
| «Lublin F, Miller DH, Freedman MS, ym. Oral fingoli...»1 | RCT | 25-65 years old patients with a clinical diagnosis of primary progressive MS disease
according to the 2005 revised McDonald criteria. Time from first reported symptoms
of 2–10 years before study entry; evidence of disability progression documented
by an increase in EDSS score of 0·5 points or more in the past 2 years; objective evidence of disability measured by EDSS score of 3·5–6; pyramidal functional system score of 2 or more; and a 25'TWT of less than 30 s. |
Oral Fingolimod 0.5 mg daily p.o. for 36 months. Oral Placebo daily for 36 months. |
The time to confirmed disability progression (CDP), components: EDSS, 25'TWT, 9-HPT. Radiological changes. Safety. |
Incomplete data |
| Reference | Comments |
|---|---|
| «Lublin F, Miller DH, Freedman MS, ym. Oral fingoli...»1 | The first 147 patients randomized to intervention started with fingolimod dose of
1.25 mg daily and were subsequently switched to 0.5 mg daily dose. 299/483 (61.9 %) randomized to fingolimod and 317/487 (65.1 %) randomized to placebo completed the study. Intention-to-treat analysis was performed. |
Results
| Reference | Number number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Hazard ratio (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval | |||||
| «Lublin F, Miller DH, Freedman MS, ym. Oral fingoli...»1 | 823 (336/487) | 36 months | 232 (69 %) | 338 (69 %) | 0.95 (0.80-1.12) |
| Level of evidence: moderate The quality of evidence is downgraded due to incomplete data. |
|||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Hazard ratio (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval | |||||
| «Lublin F, Miller DH, Freedman MS, ym. Oral fingoli...»1 | 823 (336/487) | 36 months | 154 (46 %) | 240 (49 %) | 0.88 (0.72-1.08) |
| Level of evidence: moderate The quality of evidence is downgraded due to incomplete data. |
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