Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis

Respiratory Research

Table 5 Hepatic enzyme elevation adverse events in the INPULSIS^® trials

N (%)	Nintedanib	Placebo
N (%)	(n = 638)	(n = 423)
Elevations in ALT and/or AST
≥ 3x ULN	32 (5.0)	3 (0.7)
≥ 5x ULN	14 (2.2)	1 (0.2)
≥ 8x ULN	5 (0.8)	1 (0.2)
Elevations in maximum total bilirubin
≥ 1.5x ULN	15 (2.4)	3 (0.7)
≥ 2x ULN	3 (0.5)	2 (0.5)
Elevations in maximum alkaline phosphatase
≥ 1.5x ULN	37 (5.8)	4 (0.9)
≥ 2x ULN	17 (2.7)	1 (0.2)
Normal ALT values at baseline but maximum value on treatment > ULN on treatment^a	169 (27.3)	30 (7.2)
Normal AST values at baseline but maximum value on treatment > ULN^b	134 (21.4)	22 (5.3)
Normal bilirubin values at baseline but maximum value on treatment > ULN^c	48 (7.7)	22 (5.3)
Normal alkaline phosphatase values at baseline but maximum value on treatment > ULN^d	94 (15.3)	28 (6.8)

Based on patients who received ≥1 dose of study medication. Categories are cumulative
^anintedanib n = 620, placebo n = 416; ^bnintedanib n = 625, placebo n = 418; ^cnintedanib n = 621, placebo n = 413; ^dnintedanib n = 615, placebo n = 412
Hy’s law criteria were met in no patients in the nintedanib group and in 1 patient in the placebo group. Hy’s law criteria: AST or ALT ≥3x ULN and total bilirubin ≥2x ULN measured in the same blood sample, and no other reason found to explain the combination of increased hepatic transaminases and bilirubin, such as viral hepatitis A, B or C; pre-existing or acute hepatic disease; or the use of another drug capable of causing the observed injury

ISSN: 1465-993X