Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals. Common side effects include infections, acute infusion reactions, and abdominal pain. Infliximab is a chimeric monoclonal antibody biologic. It seems to work by binding to and neutralizing TNF, preventing it from interacting with its receptors on the cell. TNF is a chemical messenger (cytokine) and a key part of the autoimmune reaction. Infliximab was originally developed in mice as a mouse antibody. Because humans have immune reactions to mouse proteins, the mouse common domains were replaced with similar human antibody domains. They are monoclonal antibodies and have identical structures and affinities to the target. Because they are a combination of mouse and human antibody amino acid sequences, they are called a "chimeric monoclonal antibody". Infliximab was approved for medical use in the United States in 1998, and in the European Union in August 1999. Infliximab biosimilars have been approved in the EU (2013), in Japan (2014), and in the United States (2016, 2017, 2019). Infliximab is a therapeutic alternative on the World Health Organization's List of Essential Medicines.
Medical uses
Crohn's disease Three phenotypes, or categories of disease, are present in Crohn's disease: stricturing disease (which causes narrowing of the bowel), penetrating disease (which causes fistulae or abnormal connections of the bowel), and inflammatory disease (which primarily causes inflammation).
Fistulizing disease Infliximab was first used for closure of fistulae in Crohn's disease in 1999. In a 94-patient, phase II clinical trial, the researchers showed infliximab was effective in closing fistulae between the skin and bowel in 56–68% of patients. A large, 296-patient Phase III clinical trial called the ACCENT 2 trial showed infliximab was additionally beneficial in maintaining closure of fistulae, with almost two-thirds of all patients treated with the three initial doses of infliximab having a fistula response after 14 weeks, and 36% of patients maintaining closure of fistulae after a year, compared with 19% who received placebo therapy. This final trial resulted in the FDA approval of the drug to treat fistulizing disease.
Inflammatory disease Infliximab has been used to induce and maintain remission in inflammatory Crohn's disease. The ACCENT 1 trial, a large, multicentre trial, found 39–45% of patients treated with infliximab, who had an initial response to it, maintained remission after 30 weeks, compared with 21% who received placebo treatment. It also showed a mean maintenance of remission from 38 to 54 weeks compared with 21 weeks for patients who received placebo treatment. Crohn's patients have flares of their disease between periods of disease quiescence. Severe flares are usually treated with steroid medications to obtain remission, but steroids have many undesirable side effects, so some gastroenterologists are now advocating the use of infliximab as the first drug to try to get patients into remission. This has been called the top-down approach to treatment.
Ulcerative colitis Infliximab targets TNF, thought to be more related to Th1 cytokines. Ulcerative colitis was thought to be a Th2 disease, and infliximab would be of limited use. However, patients with ulcerative colitis have begun to be treated with infliximab on the basis of two large clinical trials conducted in 2005 by Paul Rutgeerts and William Sandborn. The Acute ulcerative Colitis Treatment trials (ACT1 and ACT2) to evaluate the utility of infliximab in ulcerative colitis showed 44–45% of patients treated with infliximab for a year maintained a response to the medication, compared with 21% of patients who were treated with placebo medication. At two months, the response was 61–69% for patients treated with infliximab, and 31% for those treated with placebo.
Psoriatic arthritis In psoriatic arthritis (PsA), inhibitors of TNF, such as infliximab, improve the signs and symptoms. Several therapies with modest efficacy have been studied in nail psoriasis. Among available agents, higher quality data are available to support the efficacy of cyclosporine and infliximab. Based on studies in AS, the results suggest infliximab, etanercept, and adalimumab have the potential to reduce the signs and symptoms of moderate to severely active axial involvement in PsA in patients who have had an inadequate response to NSAID (level 1a, grade A). The anti-TNF agents (infliximab and etanercept; level 1b, grade A) are more effective for the treatment of enthesitis than traditional agents. Results suggest infliximab is effective for the treatment of dactylitis in PsA.
Other It was approved for treating ankylosing spondylitis, psoriatic arthritis, psoriasis, rheumatoid arthritis. Infliximab is also prescribed (out of indication) for the treatment of Behçet's disease. Infliximab is the most frequently used biological agent in treating relapsing polychondritis. Half of the patients saw benefit from this treatment, and a few other patients experienced infections that in some cases lead to death. There have been numerous case reports of the efficacy of infliximab in various inflammatory skin conditions diseases; the FDA approved infliximab for chronic severe plaque psoriasis in adults in September 2006. Infliximab has been used off-label in treating refractory sarcoidosis, where other treatments have not been effective. Infliximab has been tested in chronic obstructive pulmonary disease (COPD) but there was no evidence of benefit with the possibility of harm. Infliximab is indicated for steroid refractory checkpoint inhibitor induced colitis, at a dose of 5 to 10 mg/kg. Infliximab has been found to be a safe alternative treatment to a second dose of IVIG for Kawasaki Disease resistant to initial IVIG therapy, showing better outcomes in fever resolution and fewer severe adverse effects such as hemolytic anemia.
Adverse effects
Infliximab has adverse effects, some life-threatening, common to drugs in the class of TNF-inhibiting immunosuppressants (which also includes etanercept (Enbrel) and adalimumab (Humira)). Some of the most severe are:
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