ay beat a higher risk (up to several fold) than the general population for the development oflymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronicleukemia have been reported with postmarketing TNF-blocker use in rheumatoid arthritis andother indications. Even in the absence of TNF blocker therapy, patients with rheumatoidarthritis may be at a higher risk (approximately 2-fold) than the general population for thedevelopment of leukemia.
Hepatosplenic T-cell lymphoma (HSTCL)
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-celllymphoma, have been reported in patients treated with TNF blockers including infliximabproducts. These cases have had a very aggressive disease course and have been fatal. Almostall patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis.
The majority ofreported cases have occurred in patients with Crohn’s disease or ulcerative colitis and mostwere in adolescent and young adult males. It is uncertain whether the occurrence of HSTCLis related to TNF-blockers or TNF-blockers in combination with these otherimmunosuppressants. When treating patients, consideration of whether to use RENFLEXISalone or in combination with other immunosuppressants such as azathioprine or 6-mercaptopurine should take into account a possibility that there is a higher risk of HSTCLwith combination therapy versus an observed increased risk of immunogenicity andhypersensitivity reactions with infliximab product monotherapy from the clinical trial datafrom studies with infliximab [see Warnings and Precautions (5.7) and Adverse Reactions(6.1)].
Skin cancerMelanoma and Merkel cell carcinoma have been reported in patients treated with TNFblocker therapy, including infliximab products [see Adverse Reactions (6.2)].
Periodic skin examination is recommended for all patients, particularly those with risk factors for skin
cancer.
Cervical Cancer A population-based retrospective cohort study using data from Swedish national healthregistries found a 2 to 3 fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or thegeneral population, particularly those over 60 years of age. A causal relationship betweeninfliximab products and cervical cancer cannot be excluded. Periodic screening shouldcontinue in women treated with RENFLEXIS [see Adverse Reactions (6.2)].
Other Malignancies
In the controlled portions of clinical trials of some TNF-blocking agents including infliximabproducts, more malignancies (excluding lymphoma and nonmelanoma skin cancer [NMSC])have been observed in patients receiving those TNF-blockers compared with control patients.
During the controlled portions of infliximab trials in patients with moderately to severelyactive rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, ankylosing spondylitis,ulcerative colitis, and plaque psoriasis, 14 patients were diagnosed with malignancies(excluding lymphoma and NMSC) among 4019 infliximab-treated patients vs. 1 among 1597control patients (at a rate of 0.52/100 patient-years among infliximab-treated patients vs. arate of 0.11/100 patient-years among control patients), with median duration of follow-up 0.5years for infliximab-treated patients and 0.4 years for |
