[3] Inhibition of TNF effects can be achieved with a monoclonal antibody such as infliximab,[4] adalimumab, certolizumab pegol, and golimumab, or with a circulating receptor fusion protein such as etanercept.
[8][9][10] The role of TNF as a key player in the development of rheumatoid arthritis was originally demonstrated by Kollias and colleagues in proof of principle studies in transgenic animal models.
[13] Clinical application of anti-TNF drugs in rheumatoid arthritis was demonstrated by Marc Feldmann and Ravinder N. Maini, who won the 2003 Lasker Award for their work.
[15][16] Therapy which combines certain anti-TNF agents such as etanercept with DMARDs such as methotrexate has been shown to be more effective at restoring quality of life to sufferers of rheumatoid arthritis than using either drug alone.
[18] In 2010 The National Institute of Clinical Excellence (NICE) in the UK issued guidelines for the treatment of severe Crohn's Disease with infliximab and adalimumab.
On the other hand, adding infliximab or etanercept to gemcitabine for treating patients with advanced pancreatic cancer was not associated with differences in efficacy when compared with placebo.
[20] The U.S. Food and Drug Administration continues to receive reports of a rare cancer of white blood cells (known as hepatosplenic T-cell lymphoma or HSTCL), primarily in adolescents and young adults being treated for Crohn's disease and ulcerative colitis with TNF blockers, as well as with azathioprine, and/or mercaptopurine.
People taking TNF blockers are at increased risk for developing serious infections that may lead to hospitalization or death due to certain bacterial, mycobacterial, fungal, viral, and parasitic opportunistic pathogens.
The anti-TNF monoclonal antibody biologics infliximab, golimumab, certolizumab and adalimumab, and the fusion protein etanercept, which are all currently approved by the FDA for human use, have warnings which state that patients should be evaluated for latent TB infection, and if it is detected, preventive treatment should be initiated prior to starting therapy with these medications.
The FDA issued a warning on September 4, 2008, that patients on TNF inhibitors are at increased risk of opportunistic fungal infections such as pulmonary and disseminated histoplasmosis, coccidioidomycosis, and blastomycosis.
[36][37][38] Subsequently, an increasing number of cases were reported in IBD cohorts and in patients suffering from other chronic immune-mediated inflammatory diseases such as rheumatoid arthritis.
[45][46] Thymoquinone, a compound found in the flower Nigella sativa, has been studied for possible TNF-α inhibition and related benefits for autoimmune disorder treatment.