Infliximab

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).{{cite journal | vauthors = Dubinsky MC, Fleshner PP | title = Treatment of Crohn's Disease of Inflammatory, Stenotic, and Fistulizing Phenotypes | journal = Curr Treat Options Gastroenterol | volume = 6 | issue = 3 | pages = 183–200 | date = June 2003 | pmid = 12744819 | doi = 10.1007/s11938-003-0001-1 | s2cid = 21302609 }}

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.{{cite journal | vauthors = Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ | title = Infliximab for the treatment of fistulas in patients with Crohn's disease | journal = The New England Journal of Medicine | volume = 340 | issue = 18 | pages = 1398–405 | date = May 1999 | pmid = 10228190 | doi = 10.1056/NEJM199905063401804 | url = https://pure.uva.nl/ws/files/3156092/7456_77284y.pdf | access-date = 5 July 2019 | archive-date = 18 February 2019 | archive-url = https://web.archive.org/web/20190218233244/https://pure.uva.nl/ws/files/3156092/7456_77284y.pdf | url-status = live }} 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.{{cite journal | vauthors = Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ | title = Infliximab maintenance therapy for fistulizing Crohn's disease | journal = The New England Journal of Medicine | volume = 350 | issue = 9 | pages = 876–85 | date = February 2004 | pmid = 14985485 | doi = 10.1056/NEJMoa030815 | doi-access = free }}

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.{{cite journal | vauthors = Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P | title = Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial | journal = Lancet | volume = 359 | issue = 9317 | pages = 1541–9 | date = May 2002 | pmid = 12047962 | doi = 10.1016/S0140-6736(02)08512-4 | s2cid = 1905194 }}

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.{{cite journal | vauthors = Hanauer SB | title = Crohn's disease: step up or top down therapy | journal = Best Pract Res Clin Gastroenterol | volume = 17 | issue = 1 | pages = 131–7 | date = February 2003 | pmid = 12617888 | doi = 10.1053/bega.2003.0361 }}

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.{{cite journal | vauthors = Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF | title = Infliximab for induction and maintenance therapy for ulcerative colitis | journal = The New England Journal of Medicine | volume = 353 | issue = 23 | pages = 2462–76 | year = 2005 | pmid = 16339095 | doi = 10.1056/NEJMoa050516 | doi-access = free }}

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.{{cite journal | vauthors = Kavanaugh AF, Ritchlin CT | title = Systematic review of treatments for psoriatic arthritis: an evidence based approach and basis for treatment guidelines | journal = J. Rheumatol. | volume = 33 | issue = 7 | pages = 1417–21 | date = July 2006 | pmid = 16724373 | collaboration = GRAPPA Treatment Guideline Committee }}

It was approved for treating ankylosing spondylitis,{{cite journal | vauthors = Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, Benkhalti Jandu M, Tugwell P, Wells GA | title = TNF-alpha inhibitors for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 4 | pages = CD005468 | date = April 2015 | pmid = 25887212 | doi = 10.1002/14651858.CD005468.pub2 | pmc = 11200207 }} psoriatic arthritis, psoriasis, rheumatoid arthritis.{{cite journal | vauthors = Blumenauer B, Judd M, Wells G, Burls A, Cranney A, Hochberg M, Tugwell P | title = Infliximab for the treatment of rheumatoid arthritis | journal = The Cochrane Database of Systematic Reviews | volume = 2002 | issue = 3 | pages = CD003785 | date = 22 July 2002 | pmid = 12137712 | pmc = 8729322 | doi = 10.1002/14651858.cd003785 }}

Infliximab is also prescribed (out of indication) for the treatment of Behçet's disease.{{cite journal | vauthors = Sfikakis PP | title = Behçet's disease: a new target for anti-tumour necrosis factor treatment | journal = Ann. Rheum. Dis. | volume = 61 | issue = Suppl 2 | pages = ii51–3 | date = November 2002 | pmid = 12379622 | pmc = 1766720 | doi = 10.1136/ard.61.suppl_2.ii51 }}

Infliximab is the most frequently used biological agent in treating relapsing polychondritis.{{cite journal | vauthors = Puéchal X, Terrier B, Mouthon L, Costedoat-Chalumeau N, Guillevin L, Le Jeunne C | title = Relapsing polychondritis | journal = Joint Bone Spine | volume = 81 | issue = 2 | pages = 118–24 | date = March 2014 | pmid = 24556284 | doi = 10.1016/j.jbspin.2014.01.001 | s2cid = 205754989 | url = http://www.hal.inserm.fr/inserm-00951203 | access-date = 4 November 2018 | archive-date = 5 November 2018 | archive-url = https://web.archive.org/web/20181105015404/https://www.hal.inserm.fr/inserm-00951203 | url-status = live | url-access = subscription }} Half of the patients saw benefit from this treatment, and a few other patients experienced infections that in some cases lead to death.{{cite journal | vauthors = Kemta Lekpa F, Kraus VB, Chevalier X | title = Biologics in relapsing polychondritis: a literature review | journal = Seminars in Arthritis and Rheumatism | volume = 41 | issue = 5 | pages = 712–9 | date = April 2012 | pmid = 22071463 | doi=10.1016/j.semarthrit.2011.08.006}}

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.{{cite journal | vauthors = Gupta AK, Skinner AR | title = A review of the use of infliximab to manage cutaneous dermatoses | journal = J Cutan Med Surg | volume = 8 | issue = 2 | pages = 77–89 | year = 2004 | pmid = 15685387 | doi = 10.1007/s10227-004-0115-7 | s2cid = 23838714 }}

Infliximab has been used off-label in treating refractory sarcoidosis, where other treatments have not been effective.{{cite journal | vauthors = Wijsenbeek MS, Culver DA | title = Treatment of Sarcoidosis | journal = Clinics in Chest Medicine | volume = 36 | issue = 4 | pages = 751–767 | date = December 2015 | pmid = 26593147 | doi = 10.1016/j.ccm.2015.08.015 }}

Infliximab has been tested in chronic obstructive pulmonary disease (COPD) but there was no evidence of benefit with the possibility of harm.{{cite journal | vauthors = Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J | title = The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease | journal = Am. J. Respir. Crit. Care Med. | volume = 175 | issue = 9 | pages = 926–34 | date = May 2007 | pmid = 17290043 | doi = 10.1164/rccm.200607-995OC }}

Infliximab is indicated for steroid refractory checkpoint inhibitor induced colitis, at a dose of 5 to 10 mg/kg.{{cite journal | vauthors = Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA | title = Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline | journal = Journal of Clinical Oncology | volume = 36 | issue = 17 | pages = 1714–1768 | date = June 2018 | pmid = 29442540 | pmc = 6481621 | doi = 10.1200/JCO.2017.77.6385 }}

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.{{Cite web |date=2024-05-09 |title=Comparing Two Treatments for IVIG-Resistant Kawasaki Disease - Evidence Update for Clinicians |url=https://www.pcori.org/evidence-updates/comparing-two-treatments-ivig-resistant-kawasaki-disease |access-date=2024-06-30 |website=www.pcori.org |language=en}}

{{More citations needed section|date=November 2009}}

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:

• serious infections
• reactivation of hepatitis B
• reactivation of tuberculosis{{cite journal | vauthors = Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM | title = Tuberculosis associated with infliximab, a tumor necrosis factor α–neutralizing agent | journal = N Engl J Med | volume = 345 | issue = 15 | pages = 1098–1104 | year = 2001 | pmid = 11596589 | doi = 10.1056/NEJMoa011110 | doi-access = free }}
• lethal hepatosplenic T-cell lymphoma (generally only when combined with 6-mercaptopurine)
• drug-induced lupus
• demyelinating central nervous system disorders
• psoriasis and psoriasiform skin lesions
• new-onset vitiligo

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported with infliximab.{{cite web|url=http://www.remicade.com/remicade/global/hcp/healthcare_professionals.html|title=Remicade for Healthcare Professionals|website=Remicade|url-status=dead|archive-url=https://web.archive.org/web/20080704080738/http://www.remicade.com/remicade/global/hcp/healthcare_professionals.html|archive-date=4 July 2008}} The FDA issued a warning to doctors appearing in the respective product labeling of infliximab instructing them to screen and monitor potential patients more carefully.{{cite web | title = Remicade (infliximab) for IV Injection | date = May 2006 | publisher = U.S. Food and Drug Administration (FDA) | url = https://www.fda.gov/medwatch/safety/2006/May_PIs/Remicade_PI.pdf | archive-url = https://web.archive.org/web/20061009085444/https://www.fda.gov/medwatch/safety/2006/May_PIs/Remicade_PI.pdf| archive-date = 9 October 2006 }} The FDA issued a warning to doctors that there is an increased risk of lymphoma and other cancers associated with the use of infliximab and other tumor necrosis factor blockers in children and adolescents.{{cite web |url = https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalproducts/ucm175843.htm |title = Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi) August 2009 |date = 31 August 2009 |publisher = U.S. Food and Drug Administration (FDA) |access-date = 15 November 2009 |url-status = dead |archive-url = https://web.archive.org/web/20091115213333/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm175843.htm |archive-date = 15 November 2009 }} {{PD-notice}}

Maintenance therapy with the drug (versus intermittent or sporadic therapy) lessens the likelihood of developing antibodies to infliximab which are known to reduce the efficacy of the drug. Combination treatment with methotrexate (an antifolate drug which suppresses the immune system) has been shown to reduce the formation of these antibodies in patients with rheumatoid arthritis{{cite journal | vauthors = Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P | title = Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group | journal = Lancet | volume = 354 | issue = 9194 | pages = 1932–9 | date = 4 December 1999 | pmid = 10622295 | doi = 10.1016/s0140-6736(99)05246-0 | s2cid = 104011 }} and combination therapy with other immunosuppressants has been shown to reduce the likelihood of these antibodies being formed in Crohn's disease. The use of immunosuppressants may not be necessary in all diseases for which infliximab is indicated, and indiscriminant uses of these other immunosuppressants carry their own risks. Infliximab was studied in monotherapy (without concomitant immunosuppressants such as methotrexate or azathioprine) in psoriasis, psoriatic arthritis, and ankylosing spondylitis.

Infliximab is a purified, recombinant DNA-derived chimeric human-mouse IgG monoclonal antibody that consists of mouse heavy and light chain variable regions combined with human heavy and light chain constant regions.{{cite journal | vauthors = Akiho H, Yokoyama A, Abe S, Nakazono Y, Murakami M, Otsuka Y, Fukawa K, Esaki M, Niina Y, Ogino H | title = Promising biological therapies for ulcerative colitis: A review of the literature | journal = World Journal of Gastrointestinal Pathophysiology | volume = 6 | issue = 4 | pages = 219–227 | date = November 2015 | pmid = 26600980 | pmc = 4644886 | doi = 10.4291/wjgp.v6.i4.219 | doi-access = free }} It has a serum half-life of 9.5 days and can be detected in serum 8 weeks after infusion treatment.

Infliximab neutralizes the biological activity of TNF-α by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNF-α, and inhibits or prevents the effective binding of TNF-α with its receptors. Infliximab and adalimumab (another TNF antagonist) are in the subclass of "anti-TNF antibodies" (they are in the form of naturally occurring antibodies), and are capable of neutralizing all forms (extracellular-, transmembrane-, and receptor-bound) of TNF-α.{{cite journal | vauthors = Choy EH, Panayi GS | title = Cytokine pathways and joint inflammation in rheumatoid arthritis | journal = The New England Journal of Medicine | volume = 344 | issue = 12 | pages = 907–16 | date = March 2001 | pmid = 11259725 | doi = 10.1056/NEJM200103223441207 }} Etanercept, a third TNF antagonist, is in a different subclass (receptor-construct fusion protein), and, because of its modified form, cannot neutralize receptor-bound TNF-α.Etanercept product labeling Additionally, the anti-TNF antibodies adalimumab and infliximab have the capability of lysing cells involved in the inflammatory process, whereas the receptor fusion protein apparently lacks this capability.Etanercept, Adalimumab and Infliximab product labeling

Other monoclonal antibodies targeting TNF-α are golimumab, adalimumab, and certolizumab pegol. Etanercept also binds and inhibits the action of TNF-α, but is not a monoclonal antibody (it is instead a fusion of TNF-receptor and an antibody constant region).{{cite journal | vauthors = Peppel K, Crawford D, Beutler B | title = A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity | journal = J. Exp. Med. | volume = 174 | issue = 6 | pages = 1483–9 | year = 1991 | pmid = 1660525 | pmc = 2119031 | doi = 10.1084/jem.174.6.1483 }}

The importance of TNF in the development of rheumatoid arthritis was originally demonstrated by George Kollias and colleagues in proof of principle studies in transgenic animal models.{{cite journal |vauthors=Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G | title = Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis | journal = The EMBO Journal | volume = 10 | issue = 13 | pages = 4025–31 |date=December 1991 | pmid = 1721867 | pmc = 453150 | doi = 10.1002/j.1460-2075.1991.tb04978.x}}{{cite journal |vauthors=Brenner D, Blaser H, Mak TW | title = Regulation of tumour necrosis factor signalling: live or let die. | journal = Nat Rev Immunol | volume = 15 | issue = 6 | pages = 362–74 | date=May 2015 | pmid = 26008591 | doi=10.1038/nri3834| s2cid = 1550839 | url = https://orbilu.uni.lu/bitstream/10993/58011/1/Brenner%20and%20Blaser%20et%20al_Nature%20Reviews%20Immunol%202015.pdf }}

Infliximab was developed by Junming Le (b. 1940) and Jan Vilček (b. 1933) at New York University School of Medicine and in collaboration with Centocor (now Janssen Biotech, Inc.).{{cite journal | vauthors = Knight DM, Trinh H, Le J, Siegel S, Shealy D, McDonough M, Scallon B, Moore MA, Vilcek J, Daddona P | title = Construction and initial characterization of a mouse-human chimeric anti-TNF antibody | journal = Mol. Immunol. | volume = 30 | issue = 16 | pages = 1443–53 | date = November 1993 | pmid = 8232330 | doi = 10.1016/0161-5890(93)90106-L }}

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.{{cite press release |title = Remicade Becomes First Anti-TNF Biologic Therapy to Treat One Million Patients Worldwide |url = http://www.jnj.com/connect/NewsArchive/all-news-archive/20071106_141812 |publisher = Johnson & Johnson |date = 6 November 2007 |access-date = 14 November 2009 |url-status = dead |archive-url = https://web.archive.org/web/20110713111255/http://www.jnj.com/connect/NewsArchive/all-news-archive/20071106_141812 |archive-date = 13 July 2011 }}

{{see also|Biosimilars}}

In June 2013, two biosimilar versions (Inflectra and Remsima) were submitted for approval in the European Union, by Hospira and Celltrion Healthcare respectively.{{cite news |title=Billion-dollar biotech drug may soon have biosimilar competition | vauthors = George J |url=http://www.bizjournals.com/philadelphia/news/2013/06/28/biliion-dollar-biotech-drug-may-soon.html |work=Philadelphia Business Journal |date=28 June 2013 |access-date=27 June 2013 |url-status=live |archive-url=https://web.archive.org/web/20130701183938/http://www.bizjournals.com/philadelphia/news/2013/06/28/biliion-dollar-biotech-drug-may-soon.html |archive-date=1 July 2013 }} 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).{{cite web | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001837.jsp&mid=WC0b01ac058004d5c1 | title = European Medicines Agency recommends approval of first two monoclonal-antibody biosimilars | archive-url = https://web.archive.org/web/20150217051925/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fnews_and_events%2Fnews%2F2013%2F06%2Fnews_detail_001837.jsp&mid=WC0b01ac058004d5c1 | archive-date=17 February 2015 | work = European Medicines Agency | date = 28 June 2013 }} Celltrion obtained marketing authorization approval (MAA) from 27 EU countries and 3 EEA (European Economic Area) countries by September 2013.{{cite news | vauthors = Rockoff JD | title=European Commission Approves Biosimilar of J&J and Merck's Remicade | website=The Wall Street Journal | date=10 September 2013 | url=https://www.wsj.com/articles/european-commission-approves-biosimilar-of-jj-and-mercks-remicade-1378844400 | access-date=1 March 2020 | archive-url=https://web.archive.org/web/20170125062916/http://www.wsj.com/articles/SB10001424127887324094704579067360123704206 |archive-date=25 January 2017|url-access=subscription }}{{cite web | title=Remsima EPAR | website=European Medicines Agency (EMA) | date=4 October 2013 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/remsima | access-date=1 March 2020 | archive-date=29 December 2019 | archive-url=https://web.archive.org/web/20191229225040/https://www.ema.europa.eu/en/medicines/human/EPAR/remsima | url-status=live }}{{cite web | title=Inflectra EPAR | website=European Medicines Agency (EMA) | date=4 October 2013 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/inflectra | access-date=1 March 2020 | archive-date=16 October 2019 | archive-url=https://web.archive.org/web/20191016115847/https://www.ema.europa.eu/en/medicines/human/EPAR/inflectra | url-status=live }} Inflectra was approved for use in the European Union in September 2013, and Remsima was approved for use in the European Union in October 2013.

In Japan, Celltrion received marketing authorization for Remsima from Japan's Ministry of Health, Labour and Welfare (MHLW) in July 2014.{{citation needed|date=March 2020}}

In India, Epirus Biopharmaceuticals obtained approval to produce biosimilar infliximab under the brand name "Infimab" (trail name BOW015).{{cite web| vauthors = Serebrov M |title=Epirus racks up its first biosimilar approval in India|url=http://www.bioworld.com/content/epirus-racks-its-first-biosimilar-approval-india-0|website=BioWorld|access-date=26 October 2014|url-status=live|archive-url=https://web.archive.org/web/20141029213733/http://www.bioworld.com/content/epirus-racks-its-first-biosimilar-approval-india-0|archive-date=29 October 2014}}

The US Food and Drug Administration (FDA) approved Celltrion/Hospira/Pfizer's Inflectra (infliximab-dyyb) in April 2016.{{cite press release | title=FDA approves Inflectra, a biosimilar to Remicade | website=U.S. Food and Drug Administration (FDA) | date=6 December 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-inflectra-biosimilar-remicade | archive-url=https://web.archive.org/web/20191207001439/https://www.fda.gov/news-events/press-announcements/fda-approves-inflectra-biosimilar-remicade | archive-date=7 December 2019 | url-status=dead | access-date=6 December 2019}} {{PD-notice}}{{cite web | title=Inflectra (infliximab-dyyb) for Injection | website=U.S. Food and Drug Administration (FDA) | date=27 June 2016 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125544Orig1s000TOC.cfm | access-date=8 April 2024 | archive-date=20 May 2022 | archive-url=https://web.archive.org/web/20220520044426/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125544Orig1s000TOC.cfm | url-status=dead }}

The FDA approved Samsung Bioepis Co., Ltd.'s Renflexis (infliximab-abda) in April 2017.{{cite web | title=Drug Approval Package: Renflexis (infliximab-abda) | website=U.S. Food and Drug Administration (FDA) | date=10 December 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761054Orig1s000TOC.cfm | access-date=8 April 2024 | archive-date=18 December 2019 | archive-url=https://web.archive.org/web/20191218044927/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761054Orig1s000TOC.cfm | url-status=dead }}

Biogen released another biosimilar, Flixabi, which was approved in Germany, the UK, and the Netherlands.{{cite web|url=http://www.nasdaq.com/article/key-takeaways-from-biogens-q3-call-tecfidera-pipeline-biosimilars-cm699225/|title=Key Takeaways from Biogen's Q3 Call: Tecfidera, Pipeline, Biosimilars|date=27 October 2016|website=nasdaq.com|url-status=live|archive-url=https://web.archive.org/web/20161028083846/http://www.nasdaq.com/article/key-takeaways-from-biogens-q3-call-tecfidera-pipeline-biosimilars-cm699225/|archive-date=28 October 2016}} Flixabi was approved for use in the European Union in May 2016.{{cite web | title=Flixabi EPAR | website=European Medicines Agency (EMA) | date=9 June 2016 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/flixabi | access-date=2 April 2020 | archive-date=16 October 2019 | archive-url=https://web.archive.org/web/20191016120357/https://www.ema.europa.eu/en/medicines/human/EPAR/flixabi | url-status=live }}

In December 2017, Ixifi (infliximab-qbtx) was approved in the United States.{{cite web | title=Drug Approval Package: Ixifi (infliximab-qbtx) | website=U.S. Food and Drug Administration (FDA) | date=29 November 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761072Orig1s000TOC.cfm | access-date=8 April 2024 | archive-date=18 December 2019 | archive-url=https://web.archive.org/web/20191218044952/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761072Orig1s000TOC.cfm | url-status=dead }}

Zessly was approved for use in the European Union in May 2018.{{cite web | title=Zessly EPAR | website=European Medicines Agency (EMA) | date=30 May 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zessly | access-date=2 April 2020 | archive-date=30 December 2019 | archive-url=https://web.archive.org/web/20191230161426/https://www.ema.europa.eu/en/medicines/human/EPAR/zessly | url-status=live }}

In December 2019, Avsola (infliximab-axxq) was approved in the United States.{{cite web | title=Drug Approval Package: Avsola | website=U.S. Food and Drug Administration (FDA) | date=30 January 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761086Orig1s000TOC.cfm | access-date=8 April 2024 | archive-date=1 November 2020 | archive-url=https://web.archive.org/web/20201101090550/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761086Orig1s000TOC.cfm | url-status=dead }}

Avsola was approved for medical use in Canada in March 2020.{{cite web | title=Summary Basis of Decision (SBD) for Avsola | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00478&lang=en | access-date=29 May 2022 | archive-date=30 May 2022 | archive-url=https://web.archive.org/web/20220530221839/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00478&lang=en | url-status=live }}

In December 2021, Ixifi was approved for medical use in Canada.{{cite web | title=Summary Basis of Decision (SBD) for Ixifi | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00583&lang=en | access-date=29 May 2022 | archive-date=29 May 2022 | archive-url=https://web.archive.org/web/20220529192448/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00583&lang=en | url-status=live }}

Infliximab is supplied as a sterile, white, lyophilized (freeze-dried) powder,{{cite web|url=http://www.rxlist.com/remicade-drug.htm|title=Remicade (Infliximab): Side Effects, Interactions, Warning, Dosage & Uses|website=rxlist.com|url-status=live|archive-url=https://web.archive.org/web/20091218222855/http://www.rxlist.com/remicade-drug.htm|archive-date=18 December 2009}} so must be reconstituted and administered by a health care professional, usually in a hospital or office setting. 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.

In the UK, infliximab is available from the NHS for Crohn's disease treatment provided three criteria are met.{{cite web|url=http://guidance.nice.org.uk/TA40/Guidance|title=The clinical effectiveness and cost effectiveness of infliximab for Crohn's disease - Guidance and guidelines - NICE|website=guidance.nice.org.uk|date=26 April 2002 |url-status=live|archive-url=https://web.archive.org/web/20100430172000/http://guidance.nice.org.uk/TA40/Guidance|archive-date=30 April 2010}} 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.{{cite web|url=http://www.nice.org.uk/guidance/ta329|title=Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy |website=National Institute for Health and Care Excellence (NICE) |date=25 February 2015 |url-status=live|archive-url=https://web.archive.org/web/20150306044422/http://www.nice.org.uk/guidance/ta329|archive-date=6 March 2015}}

In Australia, infliximab is available through the PBS for Crohn's disease treatment provided the patient has not responded to conventional treatment and has a severe case of the condition.{{cite web|url=http://www.medicareaustralia.gov.au/provider/pbs/drugs1/crohns.jsp#N10041|title=Section 100 arrangements; only for infliximab|website=medicareaustralia.gov.au|url-status=dead|archive-url=https://web.archive.org/web/20110903072031/http://www.medicareaustralia.gov.au/provider/pbs/drugs1/crohns.jsp#N10041|archive-date=3 September 2011|access-date=20 August 2011}}

Johnson & Johnson reported in its 2013 annual report, "Remicade (infliximab), accounted for approximately 9.4% of the Company's total revenues for fiscal 2013."JNJ annual report, downloaded 22 April 2014. {{cite web |url=https://www.sec.gov/Archives/edgar/data/200406/000020040614000033/a2013122910-k.htm |title=2013 1229 10-K |access-date=1 September 2017 |url-status=live |archive-url=https://web.archive.org/web/20160305020323/http://www.sec.gov/Archives/edgar/data/200406/000020040614000033/a2013122910-k.htm |archive-date=5 March 2016 }}

Zymfentra was approved for medical use in the United States in October 2023.{{cite web | title=Celltrion USA Announces U.S. FDA Approval of Zymfentra (infliximab-dyyb), the First and Only Subcutaneous infliximab, for the Treatment of People With Inflammatory Bowel Disease | publisher=Celltrion | via=Business Wire | date=22 October 2023 | url=https://www.businesswire.com/news/home/20231022057773/en/Celltrion-USA-Announces-U.S.-FDA-Approval-of-ZYMFENTRA%C2%AE-infliximab-dyyb-the-First-and-Only-Subcutaneous-infliximab-for-the-Treatment-of-People-With-Inflammatory-Bowel-Disease/ | access-date=25 December 2023 | archive-date=25 December 2023 | archive-url=https://web.archive.org/web/20231225100038/https://www.businesswire.com/news/home/20231022057773/en/Celltrion-USA-Announces-U.S.-FDA-Approval-of-ZYMFENTRA%C2%AE-infliximab-dyyb-the-First-and-Only-Subcutaneous-infliximab-for-the-Treatment-of-People-With-Inflammatory-Bowel-Disease/ | url-status=live }}

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