Category:IBD medications

An IBD medication is a medicine used to treat the inflammatory bowel diseases, the chronic relapsing-remitting immune-mediated conditions of the gut comprising Crohn's disease (transmural inflammation that may affect any part of the gastrointestinal tract from mouth to anus) and ulcerative colitis (mucosal inflammation limited to the colon and rectum). The category overlaps substantially with immunosuppressants and with anti-inflammatories but contains several disease-specific agents and clinical protocols that justify its separate listing.

The pharmacological history of IBD is the gradual conversion of a uniformly progressive and surgical disease into a medically manageable one. The first effective oral medicine was sulfasalazine, synthesised in 1942 by Nanna Svartz at the Karolinska Institute in Stockholm as a combination of the sulfonamide antibacterial sulfapyridine and the anti-inflammatory 5-aminosalicylic acid (5-ASA), on the now-discredited hypothesis that rheumatoid arthritis and inflammatory bowel disease were chronic bacterial infections.^[1] The antibacterial hypothesis was wrong; the medicine, by colonic-bacterial cleavage of the azo bond into its two components and the resulting topical delivery of 5-ASA to the colonic mucosa, was effective in ulcerative colitis and in colonic Crohn's disease, and has remained in use ever since. The development of pure 5-ASA preparations from 1980 onward (mesalamine in pH-dependent delayed-release, time-dependent extended-release, and MMX multimatrix formulations; sulfa-free balsalazide; olsalazine) gave the 5-aminosalicylates their current foundational place in the treatment of mild-to-moderate ulcerative colitis and (with somewhat weaker evidence) in mild colonic Crohn's disease.

Systemic corticosteroids (described under corticosteroids) have been used in IBD since the 1955 Truelove and Witts trial of cortisone in ulcerative colitis, which demonstrated reduction in colectomy rate and mortality and established the corticosteroid as standard treatment for moderate-to-severe flares. The gut-targeted budesonide (Entocort EC, ileal-release for ileocolonic Crohn's disease; Uceris MMX, colonic-release for ulcerative colitis) provides reduced systemic glucocorticoid exposure and is used for both flares and selected maintenance indications. Systemic and gut-targeted corticosteroids remain effective for inducing remission but are inadequate as long-term maintenance therapy, both because of the chronic side-effect burden and because corticosteroid-dependent disease defines a population in need of steroid-sparing maintenance.

The first effective steroid-sparing immunomodulators in IBD were the thiopurines azathioprine and 6-mercaptopurine, used in IBD since the late 1960s on the model of their transplantation use. Their delayed onset of action (8 to 16 weeks) makes them poor agents for induction but useful for maintenance, and the now-routine TPMT and NUDT15 pharmacogenomic testing before initiation has substantially reduced the unpredictable severe myelosuppression that historically attended their use. Methotrexate is effective for maintenance of Crohn's-disease remission (the North American Crohn's Study Group methotrexate trial of 1995) but has not been demonstrated effective for ulcerative colitis.

The transformative event of contemporary IBD pharmacology was the introduction of the anti-TNF biologics. Infliximab (Centocor, 1998 for rheumatoid arthritis, 1999 for Crohn's disease, 2005 for ulcerative colitis), the chimeric monoclonal antibody whose development under Marc Feldmann and Ravinder Maini is described under DMARDs, demonstrated rapid and sustained response in moderate-to-severe Crohn's disease in the ACCENT-I and ACT trials and made closure of perianal fistulae a routine treatment outcome rather than a surgical one.^[2] Adalimumab (Abbott/AbbVie, fully human anti-TNF, IBD approval 2007), certolizumab pegol (UCB, pegylated Fab fragment, Crohn's disease 2008), and golimumab (Janssen, ulcerative colitis 2013) extended the class.

The next mechanistic addition was the gut-selective integrin antagonist. Vedolizumab (Takeda, 2014), a monoclonal antibody to the α4β7 integrin that mediates gut-specific lymphocyte trafficking, blocks lymphocyte homing to the gut without significant systemic immunosuppression; the GEMINI trials demonstrated efficacy in both Crohn's disease and ulcerative colitis and the medicine has become a first-line biologic in selected populations, particularly those with prior infection concerns. The IL-12/23 antagonist ustekinumab (Janssen, IBD approval 2016 for Crohn's, 2019 for UC) and the more selective IL-23 antagonist risankizumab (AbbVie, 2022) have similar gut-targeted efficacy with different safety profiles.

The most recent addition is the oral small-molecule class. The Janus kinase inhibitor tofacitinib (Pfizer, IBD approval 2018 for ulcerative colitis), the JAK1-selective upadacitinib (AbbVie, ulcerative colitis 2022, Crohn's disease 2023), and the sphingosine-1-phosphate receptor modulators ozanimod (Bristol-Myers Squibb, ulcerative colitis 2021) and etrasimod (Pfizer, ulcerative colitis 2023) give oral alternatives to the biologic injectables. The TYK2 inhibitor deucravacitinib and the gut-restricted ROCK inhibitor and several other classes are in trial.

The contemporary clinical management of IBD has become a treat-to-target enterprise paralleling that of rheumatology. The target is no longer just symptomatic remission but endoscopic and histologic remission and (more recently) "transmural healing" by cross-sectional imaging. The escalation algorithm is conventionally: 5-ASA for mild-to-moderate ulcerative colitis as first-line; corticosteroid induction with thiopurine or methotrexate maintenance for moderate disease; biologic induction and maintenance for moderate-to-severe disease, with progressive earlier introduction of the biologic in patients identified by clinical and biomarker risk-stratification as likely to progress; and surgery for medically refractory or complication-driven indications. The cumulative effect over thirty years is that the colectomy rate in ulcerative colitis and the perianal-fistula surgery rate in Crohn's disease have both fallen substantially, although large data sets show that the rates have plateaued rather than continued to fall, suggesting either a ceiling of medical management or an underuse of the available medicines.

By place in the treatment algorithm:

• 5-aminosalicylates (mild ulcerative colitis, selected Crohn's; topical and oral):
  • Sulfasalazine (the original; also cross-listed under DMARDs)
  • Mesalamine (various delivery: Asacol HD, Pentasa, Lialda, Apriso, Delzicol; topical Rowasa, Canasa)
  • Balsalazide (Colazal)
  • Olsalazine (Dipentum)
• Corticosteroids (induction):
  • Systemic: prednisone, prednisolone, hydrocortisone (intravenous for severe flare)
  • Gut-targeted: budesonide (Entocort EC for ileocolonic Crohn's; Uceris MMX for ulcerative colitis), beclomethasone dipropionate (rectal formulations in Europe)
  • Topical: hydrocortisone enemas, foams; budesonide rectal foam
• Immunomodulators (cross-indexed under immunosuppressants):
  • Azathioprine (TPMT/NUDT15 testing recommended before initiation)
  • 6-mercaptopurine
  • Methotrexate (Crohn's maintenance; weaker UC evidence)
  • Cyclosporine (intravenous, severe steroid-refractory UC as rescue or bridge to colectomy)
• Anti-TNF biologics (cross-indexed):
  • Infliximab (Remicade), and biosimilars
  • Adalimumab (Humira), and biosimilars
  • Certolizumab pegol (Cimzia, Crohn's disease only)
  • Golimumab (Simponi, ulcerative colitis only)
• Gut-selective anti-integrin:
  • Vedolizumab (Entyvio)
• IL-12/23 and IL-23 antagonists:
  • Ustekinumab (Stelara, IL-12/23 p40)
  • Risankizumab (Skyrizi, IL-23 p19), mirikizumab (Omvoh, IL-23 p19)
  • Guselkumab (Tremfya, IL-23 p19, IBD approval 2024)
• Oral small molecules:
  • JAK inhibitors: tofacitinib (UC), upadacitinib (UC and CD)
  • S1P-receptor modulators: ozanimod (UC), etrasimod (UC)
• Antibiotic (selected indications: pouchitis, fistulising Crohn's): metronidazole, ciprofloxacin, rifaximin
• Other:
  • Antidiarrheals (symptomatic, cautious use; see antidiarrheals)
  • Cholestyramine (for bile-acid diarrhoea in post-resection patients)

The boundary of this category is "medicine used in the treatment of inflammatory bowel disease (ulcerative colitis or Crohn's disease)." The medicines used in microscopic colitis (budesonide, cholestyramine) and diverticulitis (antibacterials) are listed under their primary indication. The medicines used in coeliac disease (the larazotide and budesonide in trial; the underlying treatment is dietary gluten avoidance rather than medicine) are not in this category. The medicines used in eosinophilic oesophagitis (proton pump inhibitors, topical/swallowed budesonide and fluticasone, dupilumab) are listed under their primary mechanism categories. The supportive-care medicines used in IBD (iron supplementation, folate, vitamin B12, anti-diarrhoeals in carefully selected patients, antiemetics, narcotic-sparing analgesia) are listed under their respective primary categories.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.