Week 11: Crohn's Disease Flashcards
State what factors is associated with the Crohn’s Disease Activity Index score.(7)
No. of liquid stools.
Ab. pain
General wellbeing
No. of extraintestinal complications.
Use of anti-diarrhoeal medications.
Presence of ab. mass.
Haematocrit
Weight
What are the points range of CDAI? (3)
0-600 points
Remission = < 150
Moderate = > 220
Severe = > 300
Outline the treatment options for inducing remission in a patient with Crohn’s Disease. (3)
1st line: CS
2nd line: Thiopurine/MTX
3rd line: Biologics
What is the first line tx for inducing remission in a px with Crohn’s Disease? (3)
CS:
- Offer monotherapy with conventional glucocorticosteroid (prednisolone, methylprednisolone or IV hydrocortisone)
- This introduces remission in px with FIRST presentation or single inflammatory exacerbation of CD in a 12-month period.
What alt. tx option can be given to px with CD if they can’t tolerate the first line? (2)
Px with ≥1 distal ileal, ileocaecal or right-sided colonic disease who decline/can’t tolerate/CS is contranidicated, give Budesonide.
Budesonide = less effective than trad. glucocorticosteroid but has fewer s/e.
Give e.g. of CS used for inducing remission in CD. (10)
Severe cases: IV Hydrocortisone 100mg (can go up to 500mg QDS)
Oral:
- Prednisolone 30-40mg daily in the morning.
- Consider oral budesonide (Entocort/Budenofalk) if prednisolone is c/i or declined = effective in ileal disease due to site of release.
- Tapering - more severe the exacerbation, the slower the schedule should be. (Av. 5mg/week)
- Need of adjusting / slow down to cover intro. of aza/6mp (3 months to effect)
Topical:
- Suppositories = proctitis
- Enemas = effective up to splenic flexures.
What other treatment option is available for px’s who decline/can’t tolerate or trad. glucocorticosteroid is c/i in CD? (2)
Give 5-Aminosalicylate for a first presentation or single inflammatory exacerbation in 12-month period.
5-ASA = less effective than trad. glucocorticosteroid/budesonide but has fewer s/e than trad. glucocorticosteroid.
Explain the 2nd line therapy which would be considered as add-on therapy for CD. (3)
Add Azathioprine/6-Mercaptopurine to trad. glucocorticosteroid or budesonide if:
- there are ≥ 2 inflammatory exacerbations in a 12-month period
- glucocorticosteroid dose can’t be tapered.
When would MTX be considered as add-on treatment for CD? (2)
Azathioprine + 6-MP = not tolerated/c/i.
Explain the 3rd line tx option for inducing remission in CD. (3)
Biologics:
- Can be used as monotherapy if 1st and 2nd line options are c/i or not tolerated.
- Can be used in combination with immunomodulators.
Explain the prescribing safety of Thiopurines. (8)
Azathioprine:
- Pro drug, metabolised by xanthine oxidase to mercaptopurine.
6-Mercaptopurine:
- Azathioprine’s metabolite
- May be better tolerated and more effective for some px.
Assess TPMT before offering Azathioprine/Mercaptopurine:
- Don’t offer Azathioprine/Mercaptopurine if TPMT is very low or absent.
- Consider AZA/6-Mer at low dose if TPMT activity = < normal but not deficient.
What pre-treatment bloods/monitoring is considered for thiopurines? (5)
FBC
LFT
CRP
U+E
Renal Finction
What pre-tx screening is used for thiopurines? (4)
Hep. B + C
HIV
Varicella
EBV
What are the dosing regimens for AZA + 6-Mer? (2)
Azathioprine = 2-2.5mg/kg daily.
6-Mercaptopurine = 1-1.5mg/kg daily.
What counselling points should be given to patient who are taking thiopurines for CD? (5)
Blood tests - weekly for 1 month, then 3 months.
Avoid direct sunlight.
Avoid live vaccines
Increased risk of infection, cancer + bone marrow suppression:
- Px warned about bone marrow suppression development i.e. infection/unexplained bleeding/bruising,
- Report to GP ASAP!
What are the common drug interactions with thiopurines? (10)
Allopurinol:
- Increased risk of toxicity
- Life-threatening
Warfarin:
- Reduced INR
- Monitor closely + may take 3 months for effect
Trimethoprim / co-trimoxazole:
- Increased risk of thrombocytopenia + neutropenia = AVOID!
Clozapine:
- Increased risk of agranulocytosis = AVOID!
Explain the process of safely prescribing MTX.
Use of AZA / 6MP = ineffective or not tolerated.
Rx Folic Acid 5mg weekly alongside (usually 2 days after MTX dose)
Monitoring:
- FBC + LFTs before and every month.
Warning:
- weekly dosing
- 1 strength of MTX is Rx and dispensed.
What are the serious s/e that px should report when taking MTX? (10)
Report for any signs of blood toxicity:
- Sore Throat
- Bruising
- Mouth Ulcers
Report for signs of liver toxicity:
- N+V
- Ab. discomfort
- Dark urine
Report for signs of respiratory effects:
- SOB
What immediate actions should be taken if a px suffers from a serious s/e of MTX? (9)
Bone marrow suppression:
- Occurs abruptly
- Clinically significant drop in WBC or platelet count = immediate withdrawal of MTX + supportive therapy.
Liver toxicity:
- Tx not started or should be discontinued if any changes to liver function occurs.
Pulmonary toxicity:
- Monitor symptoms,
- Discontinue if pneumonitis occurs.
GI toxicity:
- Withdraw if stomatitis occurs.
What are the common drug interactions of MTX? (2)
Drugs that reduce renal excretion of MTX = NSAIDs
Drugs with antifolate activity = Trimethoprim.
Explain the main function of TNF-a and how does this relate with CD. (5)
Pro-inflammatory mediator.
Overly expressed in IBD
Partially responsible for chronic inflammatory processes in the intestinal tissue.
Forms basis of biologic therapy used in CD.
Used to induce remission as monotherapy or in combination with an immunosuppressant.
What are biologics? (3)
Large, complex molecules.
Chemically synthesised:
- Made from protein + other natural substances.
- Made in a living system e.g. modified plant + animal cells.
Give e.g. of biologics used in IBD. (6)
Infliximab (Remicade)
Adalimumab (Humira)
Vedolizumab (CD) - Entyvio
Ustekinuma (CD) - Stelara
Golimumab (UC) - Simponi
(Brand Rx)
What are the licensed indications of Infliximab and Adalimumab? (3)
For adults with severe active CD
Whose disease hasn’t responded to conventional therapy
Who are intolerant of / have c/i to conventional tx.
What pre-tx checks should be made prior to starting Infliximab + Adalimumab? (10)
Chest X ray = TB*
Quantiferon Gold test - TB
Hep. B + C
HIV
Varicella, HSV
EBV
Baseline CRP, FBC, U&E, LFTs, ANA.
Weight (dosing)
Vaccine advice
Urine sample
*Use of biologics can affect the immune system. If px has latent TB, these agents can reactivate TB. Screening performed to rule TB out before initiation. If identified, TB is treated first.
What ongoing monitoring is taken place for Infliximab + Adalimumab?
FBC, ESR, CRP, LFTs every 6 months
ANA levels - yearly.
When should Inflximab / Adalimumab be given? (2)
As a planned course of tx until tx failure (incl. need for surgery) or
Until 12 months after the start of treatment, whichever is shorter.
Which patients can’t take Infliximab & Adalimumab? (8)
Crohn’s related abscess
Moderate to severe HF
Possible demyelination / multiple sclerosis
TB
Lymphoma
Recurrent Infections
Hep. B. infection (adalimumab only)
Evidence of active infection
When would you consider stopping/witholding Infliximab & Adalimumab? (6)
Px presents with an active infection.
Transaminases = raised > 3x ULN
Severe injection site reaction.
Rash
Low Neutrophil count
Ahead of elective surgery
What are the common symptoms for an infusion reaction with Infliximab? (8)
Itching
Fever
Chills
Chest Pain
Changes in BP
Problems with breathing
May be reduced by reducing the infusion rate or by stopping it for a while.
Rarely, reactions are severe, infusion is stopped.
What are the common side effects of Infliximab & Adalimumab? (10)
Headaches
Sore Throat
Dysphagia
Muscle/joint aches + pains
Leg/face swelling
Nausea, diarrhoea + ab. pain.
Worsening heart problems
Liver dysfunction
How long does it take for Infliximab + Adalimumab to leave the body? (1)
6 months.
What counselling points should be given to patients taking Infliximab + Adalimumab? (6)
Immunosuppression:
- Advise px to tell their doctor ASAP if they notice any:
- Skin rashes
- Hives
- Frequent infections
- Even if they occur several weeks after stopping the drugs.
What are the long-term effects of using Infliximab + Adalimumab? (3)
Lymphoma (higher risk)
Cancer (higher risk in COPD + Heavy smokers)
Multiple Sclerosis (higher risk)
What are biosimilars? (1)
Copy of an original biological agent already licensed for use.
Rx by brand = no substitution
Explain the potential cancer risk with IBD and its tx. (9)
Colon cancer = IBD
Immunomodulators:
- lymphoma
- non-melanoma skin cancers
- cervical dysplasia
Anti-TNF’s:
- Melanoma
Combination of both tx:
- Increases risk of solid organ malignancy.
Explain the maintenance therapy for CD. (4)
Px specific
No tx
Tx:
- Aza/6MP (MTX)
- Biologics (continued if needed to induce remission)
What do you need to do to manage medicines appropriate in IBD px? (6)
Steroids: BMs, K+ levels + supplements
OP: Tx + prevention
Px counselling: AZA/6MP
Monitoring: TPMT interpretation / checking, FBC, LFTs, U&Es
Interactions
Pregnancy/Conception
What vaccinations are advised that IBD px should receive? (5)
Influenza (inactivated) vaccine annually
Pneumococcal vaccine
Hepatitis B (in all HBV seronegative px)
HPV
Varicella zoster vaccine (if no hx of shingles or chicken pox in VZV seronegative px)
