Editing Infliximab (section)

==Medical uses==

===Crohn's disease===
Three [[phenotype]]s, or categories of disease, are present in [[Crohn's disease]]: stricturing disease (which causes narrowing of the bowel), penetrating disease (which causes [[fistula]]e or abnormal connections of the bowel), and inflammatory disease (which primarily causes [[inflammation]]).<!--
--><ref name=phenotypes>{{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 }}</ref>

====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.<!--
--><ref name=Present>{{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 }}</ref> <!--
-->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.<!--
--><ref name=ACCENT2>{{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 }}</ref>

====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.<ref name=ACCENT1>{{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 }}</ref>

Crohn's patients have flares of their disease between periods of disease quiescence. Severe flares are usually treated with [[Prednisone|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 (medicine)|remission]]. This has been called the top-down approach to treatment.<!--
--><ref name=topdown>{{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 }}</ref>

===Ulcerative colitis===
Infliximab targets [[tumour necrosis factor|TNF]], thought to be more related to [[T helper cell#Th1/Th2 Model for helper T cells|Th1]] cytokines. Ulcerative colitis was thought to be a [[T helper cell#Th1/Th2 Model for helper T cells|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.<ref name=ACT>{{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 }}</ref>

===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.<ref>{{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 }}</ref>

===Other===
It was approved for treating [[ankylosing spondylitis]],<ref name="Maxwell">{{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 }}</ref> psoriatic arthritis, psoriasis, [[rheumatoid arthritis]].<ref>{{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 }}</ref>

Infliximab is also prescribed (out of indication) for the treatment of [[Behçet's disease]].<ref>{{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 }}</ref>

Infliximab is the most frequently used biological agent in treating [[relapsing polychondritis]].<ref name="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 }}</ref> Half of the patients saw benefit from this treatment, and a few other patients experienced infections that in some cases lead to death.<ref name="Relapsing polychondritis"/><ref>{{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}}</ref>

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.<ref>{{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 }}</ref>

Infliximab has been used off-label in treating refractory [[sarcoidosis]], where other treatments have not been effective.<ref>{{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 }}</ref>

Infliximab has been tested in [[chronic obstructive pulmonary disease]] (COPD) but there was no evidence of benefit with the possibility of harm.<ref>{{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 }}</ref>

Infliximab is indicated for steroid refractory [[checkpoint inhibitor induced colitis]], at a dose of 5 to 10&nbsp;mg/kg.<ref name=Brahmer>{{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 }}</ref>

Infliximab has been found to be a safe alternative treatment to a second dose of [[Immunoglobulin therapy|IVIG]] for [[Kawasaki disease|Kawasaki Disease]] resistant to initial IVIG therapy, showing better outcomes in fever resolution and fewer severe adverse effects such as [[hemolytic anemia]].<ref>{{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}}</ref>