Takaisin

Fingolimod compared to placebo for primary progressive MS disease

Näytönastekatsaukset
Jorma Komulainen
6.2.2024

Level of evidence: B

Oral fingolimod, 0.5 mg daily for 36 months compared to placebo, appears not to slow disease progression in patients with primary progressive multiple sclerosis, when measured with the time to confirmed disability progression as a composite outcome or as an EDSS score change.

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.

Table 1. Description of the included studies
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
Table 2. Additional comments for included studies
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

Table 3. 3-month CDP (Composite)
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.
Table 4. 3-month CDS (EDSS)
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.

References

  1. Lublin F, Miller DH, Freedman MS, ym. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2016;387(10023):1075-1084 «PMID: 26827074»PubMed