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Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial.

Olsson T, Boster A, Fernández Ó, Freedman MS, Pozzilli C, Bach D, Berkani O, Mueller MS, Sidorenko T, Radue EW, Melanson M - J. Neurol. Neurosurg. Psychiatr. (2014)

Bottom Line: The time to first confirmed relapse was increased with ponesimod compared with placebo.Once-daily treatment with ponesimod 10, 20 or 40 mg significantly reduced the number of new T1 Gd+ lesions and showed a beneficial effect on clinical endpoints.NCT01006265.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden.

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Related in: MedlinePlus

(A) Cumulative number of new T1 Gd+ lesions detected by magnetic resonance image scanning at weeks 12–24 (per-protocol analysis set). Graph shows mean+SE. The percentage reduction (95%CI) versus placebo is shown for each ponesimod treatment group. (B) Dose–response analysis for the cumulative number of new T1 Gd+ lesions from week 12 to 24 (per-protocol analysis set). Black dots represent the mean value for each dose and grey dots represent the fitted models obtained in the bootstrap process. *p<0.05; **p<0.0001. T1 Gd+, T1-weighted gadolinium-enhanced.
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JNNP2013307282F3: (A) Cumulative number of new T1 Gd+ lesions detected by magnetic resonance image scanning at weeks 12–24 (per-protocol analysis set). Graph shows mean+SE. The percentage reduction (95%CI) versus placebo is shown for each ponesimod treatment group. (B) Dose–response analysis for the cumulative number of new T1 Gd+ lesions from week 12 to 24 (per-protocol analysis set). Black dots represent the mean value for each dose and grey dots represent the fitted models obtained in the bootstrap process. *p<0.05; **p<0.0001. T1 Gd+, T1-weighted gadolinium-enhanced.

Mentions: In the ponesimod groups, the mean cumulative number of new T1 Gd+ lesions at weeks 12–24 was lower in the ponesimod 10 mg (3.5), 20 mg (1.1) and 40 mg (1.4) groups compared with the placebo group (6.2) (figure 3A); the cumulative number of new T1 Gd+ lesions was significantly reduced by 43% with ponesimod 10 mg (treatment effect [ratio] 0.57, 95% CI 0.337 to 0.952; p=0.0318), by 83% with ponesimod 20 mg (treatment effect [ratio] 0.17, 95% CI 0.100 to 0.289; p<0.0001) and by 77% with ponesimod 40 mg (treatment effect [ratio] 0.23, 95% CI 0.133 to 0.384; p<0.0001) compared with placebo (figure 3A). Exploratory analyses showed a significant dose–response relationship (p<0.0001) for the primary endpoint (figure 3B). The ARR was numerically lower in each ponesimod group compared with placebo: the ARR was reduced by 37% with ponesimod 10 mg (p=0.1619), by 21% with ponesimod 20 mg (p=0.4420) and by 52% (p=0.0363) with ponesimod 40 mg (table 2).


Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial.

Olsson T, Boster A, Fernández Ó, Freedman MS, Pozzilli C, Bach D, Berkani O, Mueller MS, Sidorenko T, Radue EW, Melanson M - J. Neurol. Neurosurg. Psychiatr. (2014)

(A) Cumulative number of new T1 Gd+ lesions detected by magnetic resonance image scanning at weeks 12–24 (per-protocol analysis set). Graph shows mean+SE. The percentage reduction (95%CI) versus placebo is shown for each ponesimod treatment group. (B) Dose–response analysis for the cumulative number of new T1 Gd+ lesions from week 12 to 24 (per-protocol analysis set). Black dots represent the mean value for each dose and grey dots represent the fitted models obtained in the bootstrap process. *p<0.05; **p<0.0001. T1 Gd+, T1-weighted gadolinium-enhanced.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215282&req=5

JNNP2013307282F3: (A) Cumulative number of new T1 Gd+ lesions detected by magnetic resonance image scanning at weeks 12–24 (per-protocol analysis set). Graph shows mean+SE. The percentage reduction (95%CI) versus placebo is shown for each ponesimod treatment group. (B) Dose–response analysis for the cumulative number of new T1 Gd+ lesions from week 12 to 24 (per-protocol analysis set). Black dots represent the mean value for each dose and grey dots represent the fitted models obtained in the bootstrap process. *p<0.05; **p<0.0001. T1 Gd+, T1-weighted gadolinium-enhanced.
Mentions: In the ponesimod groups, the mean cumulative number of new T1 Gd+ lesions at weeks 12–24 was lower in the ponesimod 10 mg (3.5), 20 mg (1.1) and 40 mg (1.4) groups compared with the placebo group (6.2) (figure 3A); the cumulative number of new T1 Gd+ lesions was significantly reduced by 43% with ponesimod 10 mg (treatment effect [ratio] 0.57, 95% CI 0.337 to 0.952; p=0.0318), by 83% with ponesimod 20 mg (treatment effect [ratio] 0.17, 95% CI 0.100 to 0.289; p<0.0001) and by 77% with ponesimod 40 mg (treatment effect [ratio] 0.23, 95% CI 0.133 to 0.384; p<0.0001) compared with placebo (figure 3A). Exploratory analyses showed a significant dose–response relationship (p<0.0001) for the primary endpoint (figure 3B). The ARR was numerically lower in each ponesimod group compared with placebo: the ARR was reduced by 37% with ponesimod 10 mg (p=0.1619), by 21% with ponesimod 20 mg (p=0.4420) and by 52% (p=0.0363) with ponesimod 40 mg (table 2).

Bottom Line: The time to first confirmed relapse was increased with ponesimod compared with placebo.Once-daily treatment with ponesimod 10, 20 or 40 mg significantly reduced the number of new T1 Gd+ lesions and showed a beneficial effect on clinical endpoints.NCT01006265.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden.

Show MeSH
Related in: MedlinePlus