Therapeutics of UC/CD Flashcards
Management of Crohn’s: mild-moderate
INDUCING REMISSION
1. Prednisolone (8 weeks. PO)
2. Budenoside/5-ASA
(C/I, cannot tolerate, distal ileal/ileacecal disease)
ADD-ON THERAPY
- Azathioprine/mercaptopurine
- Methotrexate
MAINTENANCE
- Azathioprine/mercaptopurine
- Methotrexate
Management of Crohn’s: moderate-severe
INDUCING REMISSION
- Hydrocortisone (PO/IV)
- Biologics (adalimumab/vedolimumab/ustekinumab/infliximab)
ADD-ON THERAPY
- Azathioprine/mercaptopurine
- Methotrexate
MAINTENANCE
- Continuing biologics
- Azathioprine/mercaptopurine
Management of Crohn’s: fistulating disease
INDUCING REMISSION
- Antibiotics/drainage of abscess
- Biologics (infliximab/adalimumab)
ADD-ON THERAPY
1. Azathioprine/mercaptopurine
MAINTENANCE
- Continuing biologics
- Azathioprine / methotrexate
Management of UC: mild
INDUCING REMISSION
- 5-ASA
- Prednisolone/budenoside/beclomethasone
ADD-ON/MAINTENANCE
- 5-ASA
- (>2 exacerbations) Azathioprine/mercaptopurine
Management of UC: moderate
INDUCING REMISSION
- 5-ASA
- Prednisolone/budenoside/beclomethasone
- Tacrolimus
ADD-ON/MAINTENANCE
- 5-ASA
- Azathioprine/mercaptopurine
Management of UC: severe
INDUCING REMISSION
- IV Hydrocortisone
- IV Ciclosporin
- Biologics (Infliximab)
- Surgery
ADD-ON/MAINTENANCE
- Continue biologics
- Azathioprine/mercaptopurine
Benefits of Budenoside
Less effective and expensive
Used in disease affecting distal ileum, ileocecal, and ascending colon
Reduced s/e due to extensive first pass metabolism (less adrenal suppression)
5-ASA
5- aminoasalicylates (Others- olsalazine)
1) Sulfalazine (5-ASA + sulfapyridine)
- less commonly used now
- useful for patients with cross-overs e.g. suffer from RA/joint issues
2) Mesalazine (Coated 5-ASA designed for delivery in the colon)
- Released at pH 7
- Most commonly used
S/E - Blood dycrasias (abnormal material found) > brusising, bleeding, sore throat, malaise - Hypersensitivity - Reduced renal function - Hepatitis - Headaches - Dry Skin - Male infertility (reversible)
What immunosuppressant is suitable in pregnancy?
Azathioprine
When are immunosuppressants considered?
> 2 exacerbations within 2 months (meaning 2+ courses of steroids)
Steroid-dependent or resistant patients
What are the benefits of immunosuppressants?
Reduce need for steroids Mucosal healing (reduce T cell signalling)
Which immunosuppressants cannot be used in Crohn’s?
Tacrolimus or Ciclosporin
Overview: Thiopurines
Prodrug: Azathioprine
Metabolite: Mercaptopurine
- Inhibit ribonucleotide synthesis and induce T cell apoptosis
- Onset takes 2-3 months to occur
AZ 80% metabolised into MP
Extensively metabolised to active thioguanine nucleotides (checked 4-6 weeks after initiation)
TPMT (thiopurine methyl transferase) levels monitored prior to initiation (dose dependent- intermediate/deficient in enzymes require dose changes)
Side effects of immunosuppressants and monitoring
- Flu-Like symptoms (after 2-3 weeks; self limiting)
- Nausea
- Vomiting
- Idiosyncratic Pancreatitis
- Liver toxicity
- Bone marrow suppression
FBC, CRP, LFT, Thioguanine nucleotides
Overview: Methotrexate
25mg OW 16/52
Then 15mg OW 40/52
Measure methotrexate polyglutamate levels for first 8 weeks until steady state metabolism
S/E
- nausea and vomiting
- lung and liver disease
- bone marrow suppression
- mouth ulcers
- teratogenic
Overview: Ciclosporin
IV
- Steroid-resistant patients
- Duration 3-6 months
- Alternative: Tacrolimus
At what point must cover against infection be considered?
When on 3 immunosuppressants e.g. ciclosporin, azathioprine and steroid
Use co-trimoxazole
Risk of PCP (pneumocystis pneumonia)
Overview: Available biological therapies
ALL ANTI-TNFa
Patients progressively loose response overtime due to development of antibodies (immunosuppressants used when possible)
1) Infliximab
- genetically engineered murine-human monoclonal antibody antibody
- IV infusion 0, 2, 6, 8 weekly
- Must screen for latent infections such as TB, psoriasis, dermatitis, neuropathy
2) Adalimumab
- fully humanised monoclonal antibody
- better s/e compared to infliximab
- can be administered at home weekly
3) Golimumab
- S/C injection
- 4 weekly
- weight dependent
4) Vedolizumab
- 8 weekly infusion
- Preferred in geriatrics: gut-specific
- Binds to ‘gut homing’ lymphocytes and blocks recruitment of inflammatory cells
- Reduced s/e
Contraindications against biological therapies
Active infection
Moderate/severe heart failure
Hypersensitivity
Pre-screening before biological therapies
HIV Shingles Hepatitis B and C Chickenpox Tuberculosis Active malignancy
FBC
LFTs
CRP
Renal function
Different antibiotics that can be used
- Metronidazole
- 6 months after surgery
- 3 months after anastomosis surgery
- Active fistulating disease
- Bacterial overgrowth - Ciprofloxacin +/- Rifampicin
- Anti-MAP therapy
- treating bacterial overgrowth
- long course, low dose
Adjunctive treatments (holistic)
Smoking cessation
Diet (i.e. FODMAP diet)
Antimotility and antispasmodic drugs (codeine, loperamide)
Cholestyramine (diarrhoea due to bile acid malabsorption, especially after ileal resection)
Iron and vitamins
Stress management
Indications for surgery in UC
Types
Unresponsive to medical therapy
UC: toxic megacolon
Colorectal Cancer
- Colectomy (partial/full removal)
- maintain full anal function and consistency - Ileostomy
- permanent stoma fitted
- can cause malabsorption problems
Indications for surgery in CD
- Unresponsive to medical therapy
- Disease is treatable by surgery
- Severe perianal infection, cancer, obstruction, fistulae, abscess, strictures, perforations
- Short bowel syndrome
- Stoma
Limitations and risks of surgery
- Pouchitis
- Faecal incontinence
- Prolapse
- Anastomatic stricture/leak
Aims of treatment
Aggressive treatment during flare
Inducing remission
Maintaining and symptomatic treatment in remission
Choice of therapy depends on…
Severity of disease
Disease extent and location
Patient preference
Response to treatment
Generally, what do corticosteroids do?
Inhibit phospholipase A2 activity and AA-PG cascade
