s patients as compared to patients with otherdiseases treated with infliximab over the long term is not known.
The data reflect the percentage of patients whose test results were positive for antibodies toinfliximab in an immunoassay, and they are highly dependent on the sensitivity andspecificity of the assay. Additionally, the observed incidence of antibody positivity in anassay may be influenced by several factors including sample handling, timing of samplecollection, concomitant medication, and underlying disease. For these reasons, comparison ofthe incidence of antibodies to infliximab products with the incidence of antibodies to otherproducts may be misleading.
HepatotoxicitySevere liver injury, including acute liver failure and autoimmune hepatitis, has been reportedin patients receiving infliximab products [see Warnings and Precautions (5.4)]. Reactivationof hepatitis B virus has occurred in patients receiving TNF-blocking agents, includinginfliximab products, who are chronic carriers of this virus [see Warnings and Precautions(5.3)].
In clinical trials in rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosingspondylitis, plaque psoriasis, and psoriatic arthritis, elevations of aminotransferases wereobserved (ALT more common than AST) in a greater proportion of patients receivinginfliximab than in controls (Table 1), both when infliximab was given as monotherapy andwhen it was used in combination with other immunosuppressive agents. In general, patientswho developed ALT and AST elevations were asymptomatic, and the abnormalities decreasedor resolved with either continuation or discontinuation of infliximab, or modification ofconcomitant medications.
Table 1 Proportion of patients with elevated ALT in clinical trials
Proportion of patients with elevated ALT
> 1 to < 3 x ULN ≥ 3 x ULN ≥ 5 x ULN
Placebo Infliximab Placebo Infliximab Placebo Infliximab
Rheumatoi
d arthritisa
24% 34% 3% 4% < 1% < 1%
Crohn’s
diseaseb
34% 39% 4% 5% 0% 2%
Ulcerative
colitisc
12% 17% 1% 2% < 1% < 1%
Ankylosin
g
spondylitis
d
15% 51% 0% 10% 0% 4%
Psoriatic
arthritise
16% 50% 0% 7% 0% 2%
Plaque
psoriasisf
24% 49% <1% 8% 0% 3%
a Placebo patients received methotrexate while infliximab patients received both infliximab and methotrexate.Median follow-up was 58 weeks.
b Placebo patients in the 2 Phase 3 trials in Crohn’s disease received an initial dose of 5 mg/kg infliximab atstudy start and were on placebo in the maintenance phase. Patients who were randomized to the placebomaintenance group and then later crossed over to infliximab are included in the infliximab group in ALT
analysis. Median follow-up was 54 weeks. c Median follow-up was 30 weeks. Specifically, the median duration of follow-up was 30 weeks for placebo
and 31 weeks for infliximab. d Median follow-up was 24 weeks for the placebo group and 102 weeks for the infliximab group. e Median follow-up was 39 weeks for the infliximab group and 18 weeks for the placebo group. fALT values are obtained in 2 Phase 3 psoriasis studies with median follow-up of 50 weeks for infliximab
and 16 weeks for placebo.
Adverse Reactions in Psoriasis Studies
During the placebo-controlled portion across the 3 clinical trials up to Week 16, theproportion of patients who experienced at least 1 serious adverse reaction (SAE; defined asresulting in death, life threatening, requires hospitalization, or persi |
