infectionswere reported; 2 cases each of coccidioidomycosis (1 case was fatal) and histoplasmosis (1case was fatal), and 1 case each of pneumocystosis, nocardiosis and cytomegalovirus.
Tuberculosis was reported in 14 patients, 4 of whom died due to miliary tuberculosis. Othercases of tuberculosis, including disseminated tuberculosis, also have been reported postmarketing.
Most of these cases of tuberculosis occurred within the first 2 months afterinitiation of therapy with infliximab and may reflect recrudescence of latent disease [see
Warnings and Precautions (5.1)].
In the 1year placebo-controlled studies RA I and RA II, 5.3%of patients receiving infliximab every 8 weeks with MTX developed serious infections as
compared to 3.4% of placebo patients receiving MTX. Of 924 patients receiving infliximab,1.7% developed pneumonia and 0.4% developed TB, when compared to 0.3% and 0.0% inthe placebo arm respectively. In a shorter (22-week) placebo-controlled study of 1082 RApatients randomized to receive placebo, 3 mg/kg or 10 mg/kg infliximab infusions at 0, 2, and6 weeks, followed by every 8 weeks with MTX, serious infections were more frequent in the10 mg/kg infliximab group (5.3%) than the 3 mg/kg or placebo groups (1.7% in both). Duringthe 54-week Crohn’s II Study, 15% of patients with fistulizing Crohn’s disease developed anew fistula-related abscess.
In infliximab clinical studies in patients with ulcerative colitis, infections treated withantimicrobials were reported in 27% of infliximab-treated patients (average of 41 weeks offollow-up) and in 18% of placebo-treated patients (average 32 weeks of follow-up). Thetypes of infections, including serious infections, reported in patients with ulcerative colitiswere similar to those reported in other clinical studies.
The onset of serious infections may be preceded by constitutional symptoms such as fever,chills, weight loss, and fatigue. The majority of serious infections, however, may also bepreceded by signs or symptoms localized to the site of the infection.
Autoantibodies/Lupus-like Syndrome
Approximately half of infliximab-treated patients in clinical trials who were antinuclearantibody (ANA) negative at baseline developed a positive ANA during the trial comparedwith approximately one-fifth of placebo-treated patients. Anti-dsDNA antibodies were newlydetected in approximately one-fifth of infliximab-treated patients compared with 0% ofplacebo-treated patients. Reports of lupus and lupus-like syndromes, however, remainuncommon.
Malignancies
In controlled trials, more infliximab-treated patients developed malignancies than placebotreatedpatients [see Warnings and Precautions (5.2)].
In a randomized controlled clinical trial exploring the use of infliximab in patients withmoderate to severe COPD who were either current smokers or ex-smokers, 157 patients weretreated with infliximab at doses similar to those used in rheumatoid arthritis and Crohn’sdisease. Of these infliximab-treated patients, 9 developed a malignancy, including1 lymphoma, for a rate of 7.67 cases per 100 patient-years of follow-up (median duration offollow-up 0.8 years; 95% CI 3.51 -14.56). There was 1 reported malignancy among77 control patients for a rate of 1.63 cases per 100 patient-years of follow-up (medianduration of follow-up 0.8 years; 95% CI 0.04 -9.10). The majority of the malignanciesdeveloped in the lung or head and neck.
In a randomized study |
