Ulcerative colitis is a lifelong inflammatory disease affecting the rectum and colon to a variable extent. In 2023, the prevalence of ulcerative colitis was estimated to be 5 million cases around the world, and the incidence is increasing worldwide. Ulcerative colitis is thought to occur in people with a genetic predisposition following environmental exposures; gut epithelial barrier defects, the microbiota, and a dysregulated immune response are strongly implicated. Patients usually present with bloody diarrhoea, and the diagnosis is based on a combination of clinical, biological, endoscopic, and histological findings. The aim of medical management is, first, to induce a rapid clinical response and normalise biomarkers and, second, to maintain clinical remission and reach endoscopic normalisation to prevent long-term disability. Treatments for inducing remission include 5-aminosalicylic acid drugs and corticosteroids. Maintenance treatments include 5-aminosalicylic acid drugs, thiopurines, biologics (eg, anti-cytokines and anti-integrins), and small molecules (Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators). Although the therapeutic options are expanding, 10–20% of patients still require proctocolectomy for medically refractory disease. The keys to breaking through this therapeutic ceiling might be the combination of therapeutics with precision and personalised medicine.

1. DRUG TREATMENT OF
INFLAMMATORY BOWEL
DISEASE

2. Objectives
 Describe the mechanism of action,
pharmacokinetics and adverse effects
of drugs in IBD

3. INFLAMMATORY BOWEL DISEASE
 Ulcerative Colitis
 Crohn’s disease

4. Inflammatory bowel disease
 Inappropriate inflammatory response to
intestinal microbes in a genetically
susceptible host

5. Ulcerative colitis
- diffuse mucosal
inflammation
- limited to colon
- defined by location
(eg
proctitis;pancolitis)

7. Crohn’s disease
- patchy transmural
inflammation
- fistulae, strictures
- any part of GI tract

8. AIMS OF THERAPY
 Suppress inflammatory response
 Suppress the immune reaction

9.  Aminosalicylates corticosteroids
 Acute maintenance acute

10. Aminosalicylates
• precise MOA unknown
• act on epithelial cells
• anti-inflammatory
• modulate release of cytokines and reactive
oxygen species

11. Aminosalicylates
 Local effect on mucosa in reducing inflammation

12. Sulphasalazine
 Broken down by gut bacterial azoreductase to 5-
aminosalicylate & sulphapyridine

13. SULFASALAZINE
Bacterial Flora
(Colon)
Bacterial azoreductase
Sulfapyridine 5-aminosalicylic Acid
Absorbed Acts through the lumen
Systemic Adverse Effect Anti-inflammatory Effect

14. Aminosalicylates
 5-ASA absorbed in small intestine
 Acetylated by N- acetyltransferase-1
 Excreted in urine

15. Indications
 Maintaining remission in UC
 Reduce risk of colorectal cancer by 75%
(long term Rx for extensive disease)
 Less effective for maintenance in CD
 Inducing remission in mild UC/CD (higher
doses)

16. Contraindications
/cautions
 5-ASA
- Salicylate hypersensitivity
 Sulfapyridine
- G6PD deficiency (haemolysis)
- Slow acetylator status ( risk of
hepatic and blood disorders)

17. Adverse effects
 Dose-related
 Idiosyncratic (rare)
- blood disorders
- skin reactions – lupus like syndrome;
Stevens-Johnson syndrome; alopecia

18. Blood disorders
 Agranulocytosis; aplastic anaemia;
leucopenia; neutropenia;
thrombocytopenia; methaemoglobinemia
 Patients should advised to report any
unexplained bleeding; bruising; purpura;
sore throat; fever or malaise

19. Steven’s Johnson syndrome
 immune-complex–
mediated
hypersensitivity
 erythema
multiforme
 target lesions,
mucosal
involvement

20. Newer formulations
 Mesalazine (5-ASA)
 Balsalazide (a prodrug of 5-ASA)
 Olsalazine (5-ASA dimer)

21. Mesalazine
 Available as
 Enteric-coated tablets (for ileal Crohn’s disease)
 Slow release tablets (for proximal bowel Crohn’s)
 Enemas, suppositories (for distal colonic disease)
 Used when sulphasalazine can not be
tolerated

22. Sulfasalazine
 Oral use
Mesalamine (5-aminosalicylic acid).
 Oral delayed release capsules
 Enema
Olsalazine.
 5-ASA-n=n-5-ASA
 Bacterial flora breaks it into 5-ASA
Aminosalicylates

23. Anti-inflammatory &
Immunosuppressive Drugs
 Corticosteroids
 Prednisolone
 Hydrocortisone

24. Corticosteroids
USES
 Remission Induction
 Route of Administration
Oral
Intravenous
Topical (Enema)

25. Indications
 Moderate to severe relapse UC & CD
 No role in maintenance therapy
 Combination oral and rectal
Indications

26. Immunomodulators
 Azathioprine
 Cyclosporine
 Infliximab (Anti-TNF-)

27. Thiopurines
Azathioprine
 MOA: inhibit ribonucleotide synthesis;
induce T cell apoptosis by modulating
cell (Rac1) signalling

28. Indications
 Steroid sparing agents
 Active disease CD/UC
 Maintenance of remission CD/UC
 Generally continue treatment x 3-4years

29. Ciclosporin
 MOA:inhibitor of calcineurin
preventing clonal expansion of T
cells
 Indicated in Severe UC
 No value in CD

30. Methotrexate
 MOA: inhibitor of dihyrofolate reductase;
anti-inflammatory
 Inducing remission/preventing relapse
in CD
 Refractory to or intolerant of
Azathioprine

31. Infliximab
 Indicated active and fistulating CD
- in severe CD refractory or intolerant
of steroids & immunosupressants
- for whom surgery is inappropriate
 MOA: anti-TNF monoclonal antibody
 Potent anti-inflammatory

32. Antibiotics
 Metronidazole
 Ciprofloxacin
 Clarithromycin
 “Probiotics” (administration of “healthy”
bacteria)

33.  Summary

34. Drugs for IBD
 Aminosalicylates
 Glucocorticoids
 Immunosuppressives
 Cytokine modulators
 Antibiotics

35. Management of UC
to induce remission
1. oral +- topical 5-ASA
2. +- oral corticosteroids
3. Azathioprine
4. iv steroids/Colectomy/ ciclosporin
(severe)

36. Maintaining remission
1. oral +- topical 5-ASA
2. +- Azathioprine (frequent relapses)

37. Management of CD
to induce remission
1. oral high dose of 5-ASA
1. +- oral corticosteroids reducing over 8/52
2. Azathioprine
3. iv steroids/ metronidazole/elemental
diet/surgery/infliximab

38. Maintaining remission
+- Azathioprine (frequent relapses)
Methotrexate (intolerant of
azathioprine)
Infliximab infusions (8 weekly)