eva luating infliximab in moderate to severe heart failure (NYHA ClassIII/IV; left ventricular ejection fraction ≤ 35%), 150 patients were randomized to receivetreatment with 3 infusions of infliximab 10 mg/kg, 5 mg/kg, or placebo, at 0, 2, and 6 weeks.
Higher incidences of mortality and hospitalization due to worsening heart failure wereobserved in patients receiving the 10 mg/kg infliximab dose. At 1 year, 8 patients in the10 mg/kg infliximab group had died compared with 4 deaths each in the 5 mg/kg infliximaband the placebo groups. There were trends toward increased dyspnea, hypotension, angina,and dizziness in both the 10 mg/kg and 5 mg/kg infliximab treatment groups, versus placebo.
Infliximab has not been studied in patients with mild heart failure (NYHA Class I/II) [seeContraindications (4) and Warnings and Precautions (5.5)].
Immunogenicity
Treatment with infliximab products can be associated with the development of antibodies tothese products. An enzyme immunoassay (EIA) method was originally used to measure antiinfliximabantibodies in clinical studies of infliximab. The EIA method is subject tointerference by serum infliximab, possibly resulting in an underestimation of the rate ofpatient antibody formation. A separate, drug-tolerant electrochemiluminescenceimmunoassay (ECLIA) method for detecting antibodies to infliximab was subsequentlydeveloped and validated. This method is 60-fold more sensitive than the original EIA. Withthe ECLIA method, all clinical samples can be classified as either positive or negative forantibodies to infliximab without the need for the inconclusive category.
The incidence of antibodies to infliximab in patients given a 3-dose induction regimenfollowed by maintenance dosing was approximately 10% as assessed through 1 to 2 years oftreatment with infliximab. A higher incidence of antibodies to infliximab was observed inCrohn’s disease patients receiving infliximab after drug-free intervals >16 weeks. In a studyof psoriatic arthritis in which 191 patients received 5 mg/kg with or without MTX, antibodiesto infliximab occurred in 15% of patients. The majority of antibody-positive patients had lowtiters. Patients who were antibody-positive were more likely to have higher rates of clearance,reduced efficacy and to experience an infusion reaction [see Adverse Reactions (6.1)] thanwere patients who were antibody negative. Antibody development was lower amongrheumatoid arthritis and Crohn’s disease patients receiving immunosuppressant therapiessuch as 6-MP/AZA or MTX.
In the psoriasis Study II, which included both the 5 mg/kg and 3 mg/kg doses, antibodieswere observed in 36% of patients treated with 5 mg/kg every 8 weeks for 1 year, and in 51%of patients treated with 3 mg/kg every 8 weeks for 1 year. In the psoriasis Study III, whichalso included both the 5 mg/kg and 3 mg/kg doses, antibodies were observed in 20% ofpatients treated with 5 mg/kg induction (weeks 0, 2 and 6), and in 27% of patients treatedwith 3 mg/kg induction. Despite the increase in antibody formation, the infusion reactionrates in Studies I and II in patients treated with 5 mg/kg induction followed by every 8 weekmaintenance for 1 year and in Study III in patients treated with 5 mg/kg induction (14.1%-23.0%) and serious infusion reaction rates (<1%) were similar to those observed in other study populations. The clinical significance of apparent increased immunogenicity onefficacy and infusion reactions in psoriasi |
