Infliximab — BrandWiki

Infliximab

verifiedfields	changed
verifiedrevid	458271995
type	mab
mab type	mab
source	xi/o
target	Tumor necrosis factors (TNF)
tradename	Remicade, others
medlineplus	a604023
dailymedid	Infliximab
pregnancy au	C
pregnancy au comment	‡R1R‡
routes of administration	Intravenous, subcutaneous
atc prefix	L04
atc suffix	AB02
biosimilars	infliximab-abda, infliximab-axxq, infliximab-dyyb, infliximab-qbtx, Avsola, Flixabi, Inflectra, Ixifi, Remsima, Renflexis,‡R2R‡‡R3R‡ Zessly, Zymfentra
legal au	S4
legal ca	Rx-only
legal ca comment	/ Schedule D‡R4R‡‡R5R‡‡R6R‡
legal uk	POM
legal us	Rx-only
legal us comment	‡R7R‡‡R8R‡‡R9R‡‡R10R‡‡R11R‡
legal eu	Rx-only
bioavailability	92% (IV, if 8% left in the syringe)
metabolism	reticuloendothelial system
elimination half-life	9.5 days
cas number	170277-31-3
drugbank	DB00065
chemspiderid	none
unii	B72HH48FLU
kegg	D02598
chembl	1201581
c	6428
h	9912
n	1694
o	1987
s	46

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".[12]

Infliximab was approved for medical use in the United States in 1998,[13]

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).[16]

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.[17] 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.[18]

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.[19]

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.[20]

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.[17] 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.[18]

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.[19]

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.[20]

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.[21]

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.[22]

Other

It was approved for treating ankylosing spondylitis,[23] psoriatic arthritis, psoriasis, rheumatoid arthritis.[24]

Infliximab is also prescribed (out of indication) for the treatment of Behçet's disease.[25]

Infliximab is the most frequently used biological agent in treating relapsing polychondritis.[26] Half of the patients saw benefit from this treatment, and a few other patients experienced infections that in some cases lead to death.[26][27]

Society and culture

Marketing

Remicade is marketed by Janssen Biotech, Inc. (formerly Centocor Biotech, Inc.) in the United States, Mitsubishi Tanabe Pharma in Japan, Xian Janssen in China, and Schering-Plough (now part of Merck & Co) elsewhere.[46]

Biosimilars

In June 2013, two biosimilar versions (Inflectra and Remsima) were submitted for approval in the European Union, by Hospira and Celltrion Healthcare respectively.[47] Both had a positive opinion from European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) for sale in the European Union (EU).[48] Celltrion obtained marketing authorization approval (MAA) from 27 EU countries and 3 EEA (European Economic Area) countries by September 2013.[49][50][51] Inflectra was approved for use in the European Union in September 2013,[51] and Remsima was approved for use in the European Union in October 2013.[50]

In Japan, Celltrion received marketing authorization for Remsima from Japan's Ministry of Health, Labour and Welfare (MHLW) in July 2014.

In India, Epirus Biopharmaceuticals obtained approval to produce biosimilar infliximab under the brand name "Infimab" (trail name BOW015).[52]

The US Food and Drug Administration (FDA) approved Celltrion/Hospira/Pfizer's Inflectra (infliximab-dyyb) in April 2016.[53][54]

The FDA approved Samsung Bioepis Co., Ltd.'s Renflexis (infliximab-abda) in April 2017.[55]

Biogen released another biosimilar, Flixabi, which was approved in Germany, the UK, and the Netherlands.[56] Flixabi was approved for use in the European Union in May 2016.[57]

In December 2017, Ixifi (infliximab-qbtx) was approved in the United States.[58]

Zessly was approved for use in the European Union in May 2018.[59]

In December 2019, Avsola (infliximab-axxq) was approved in the United States.[60]

Avsola was approved for medical use in Canada in March 2020.[61]

In December 2021, Ixifi was approved for medical use in Canada.[62]

Availability/affordability

Infliximab is supplied as a sterile, white, lyophilized (freeze-dried) powder,[63] so must be reconstituted and administered by a health care professional, usually in a hospital or office setting.[46] For this reason, it is usually covered under major medical insurance rather than prescription drug coverage. The loading regimen for all approved indications occurs at weeks 0, 2, and 6 at the above dosages.[46]

In the UK, infliximab is available from the NHS for Crohn's disease treatment provided three criteria are met.[64] Patients should have severe active Crohn's disease with a CDAI score of 300 or more, have not responded to immunomodulating drugs and corticosteroids, and for whom surgery is inappropriate. Since February 2015, it is also approved for the treatment of ulcerative colitis where other treatments have not worked.[65]