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Abstract Details

Analysis and Evaluation of Ponesimod Hepatic Safety Data
Multiple Sclerosis
P1 - Poster Session 1 (9:00 AM-5:00 PM)
283
In the phase III OPTIMUM study, we evaluated alanine transaminase (ALT) elevations with ponesimod 20mg compared with teriflunomide 14mg.
Elevations of ALT have been observed with sphingosine 1-phosphate (S1P) receptor modulators.
Individual case reviews of ALT profiles of ponesimod-treated patients with at least one treatment-emergent ALT ≥3x ULN occurrence up to end of treatment (EOT) + 1 day was conducted. Time to first resolution was defined as the time to first ALT <3x ULN after elevation to ALT ≥3x ULN was observed, i.e. [date of first ALT <3x ULN − date of first ALT ≥ 3x ULN + 1] in days. Patients without any ALT <3x ULN (i.e. those not resolved) were censored at the EOT + 1 day, and time was defined as [date of EOT − date of first ALT ≥3x ULN + 2] in days. To examine the impact of laboratory reference range change on the results, liver test abnormalities were also summarized using the ULN definitions employed in the phase II study. The impact of lowering the frequency of assessment to the phase II study was also evaluated.
In ponesimod-treated patients, the median time to an elevation of 3x ULN was 3 months. 89% of patients with ALT increases ≥3x ULN continued treatment with ponesimod with values returning to <3x ULN within approximately 2-4 weeks. As expected, the apparently higher proportion of outliers observed in OPTIMUM is due to the change in definitions of ULN in the central laboratory and more frequent testing compared to other studies.
The pattern of hepatic effects observed with ponesimod treatment in the development program is consistent with the S1P class and no cautionary statement on adverse reactions for moderate and severe hepatic impairment categories was included in the label.
Authors/Disclosures

PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
Maria Ait Tihyaty (Johnson and Johnson Innovative Medicine) Dr. Ait Tihyaty has received personal compensation for serving as an employee of Dianthus Therapeutics.