Amongst the first monoclonal antibody used in the treatment of rheumatoid arthritis was Remicade. At the onset of the treatment, it is administered intravenously at the intervals of zero, two and six weeks, followed by every eight weeks subsequently. During the first year of the course, patients are scheduled to receive six infusions in all.

FDA approved the use of Remicade, during November 1999. The agency approved the use of Remicade (infliximab) with methotrexate for the treatment of rheumatoid arthritis in patients who had an inadequate response to methotrexate alone. This approval was based on the results of a clinical trial called ATTRACT i.e. Anti- TNF Trial in Rheumatoid Arthritis with Concomitant Therapy. It was a double-blind, placebo-controlled, randomized clinical trial involving 428 patients at 34 clinical sites. During the study, post 30 weeks of treatment, 50% of patients treated with Remicade (infliximab) and methotrexate when compared to 20% of patients receiving only methotrexate, exhibited reduced signs and symptoms of rheumatoid arthritis. This assessment was done using a standard procedure called ACR20.

However, when several reports of serious infections caused by viruses, fungi, or bacteria that spread through the body, including tuberculosis (TB) and histoplasmosis mainly in adolescent and young male patients suffering from Crohn’s disease or ulcerative colitis, were brought to the notice of FDA, the agency issued a Black Box Warning to the drug, during early September 2008. Post marketing studies also revealed some cases of hepatosplenic T-cell lymphoma which was a very aggressive disease course and could also prove very fatal. Of 240 reported cases of a distinct fungal infection known as histoplasmosis, approximately 20% of the patients i.e. 45/240 patients died.

FDA, in addition to issuing a black box warning to the drug also notified all the health professionals that tuberculosis and other serious infections like histoplasmosis, listeriosis, and pneumocystosis, have been reported in both the clinical research and post-marking surveillance settings, and that some of these infections have proved to be fatal. The FDA’s notification also clarified that though the medication provided relief from the symptoms of rheumatoid arthritis, Crohn’s disease, and juvenile arthritis, it in turn increased the possibility for infection due to the weakened state of the immune system, which was potentially deadly in several cases.

The full prescribing information of Remicade reads as follows:



Patients treated with REMICADE (infliximab) ® are at increased risk for developing serious infections that may lead to hospitalization or death [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. REMICADE (infliximab) should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:

  • Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before REMICADE (infliximab) use and during therapy.1,2 Treatment for latent infection should be initiated prior to REMICADE (infliximab) use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with REMICADE (infliximab) should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with REMICADE (infliximab) , including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.


Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE [see WARNINGS AND PRECAUTIONS].

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE (infliximab) . These cases have had a very aggressive disease course and have been fatal. All reported REMICADE (infliximab) cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE (infliximab) at or prior to diagnosis.