1. Crohn’s Disease Biologic Pathway
Anti-TNFs in Crohn’s Disease used for:
Severe active CD: HBI = >8 CDAI = >300
Inadequate response for tolerance of contraindication to conventional therapies
Chronic active CD with failure to control with immunosuppression
Consider earlier biological use in the young (<40), those with fulminant disease or those with anastomic recurrence despite immunosuppression.
Treatment should be started with the least expensive appropriate drug.
Consider IFX for – penetrating/fistulating disease, patient with poor compliance/difficulties administering S/C.
Anti-TNF therapy should be given as a planned course until failure.
Reassess at 12 months and continue therapy only if evidence of on-going active disease (clinical /lab tests/investigations)
Biosimilar anti-TNF may be prescribed (switching of stable patients should be discussed with the patient)
Golimumab is not licensed in CD.
Pathway A
Crohn’s Disease Biologic Pathway
Severe active Crohn’s (TA 187, TA 456)
Failure or intolerance of immunosuppression
Adalimumab SC , Infliximab IV, ustekinumab
Active Fistulating (TA 187, TA 352, TA 456)
Infliximab = 1st Line
Consider Adalimumab/Vedolizumab/ ustekinumab
Assess response at 12 weeks = NICE REVIEW
Review may be at weeks for vedolizumab
Clinical response (HBI)
Bloods +/- faecal calprotecin
Good Response
Poor Response
Primary Non-Response
Add/optimize immunosuppressant
(if suitable + not already on)
Optimise Anti-TNF (drug trough + antibody levels )
Alternative biologic Vedolizumab (TA 352) or ustekinumab (TA 456)
Surgery
Good Clinical Response
Assess response after /52
eg. repeat drug and antibody levels
Continue scheduled prescribing + clinical review for response
Poor Response
Clinical response (HBI)
Faecal calprotectin
Colonoscopy/Radiology (Small Bowel)
Reassess response at 12/12 = NICE REVIEW
Alternative biologic Vedolizumab (TA 352)
Clinical Trial
Surgery
Remission*
Partial/Incomplete Response
No Response
Consider stopping biologic + maintaining immunosuppressant
Continue + optimise biologic therapy +/- immunosuppressant.
Consider switching therapy.
Switch to alternative biologic Vedolizumab (TA 352) or ustekinumab (TA456)
*Remission for biologic cessation is defined as asymptomatic and biochemical and /or radiological evidence of healing.

2. Ulcerative Colitis Biologics Pathway NICE CG 166
Pathway B
Ulcerative Colitis Biologics Pathway
NICE CG 166
Moderately to severe active UC
Acute severely active UC, if not responding to IV steroids
Anti-TNF (TA329)
Infliximab(IV), Golimumab (s/c), Adalimumab (s/c)
Vedolizumab (IV) (TA342)
Infliximab (IV) (TA 183)
5mg/kg at week 0, 2, 6
Ciclosporin (IV)
2mg/kg 24 hours IV
Consider giving second dose at week 1 if patient has high CRP and low serum albumin
Assess response by 12/52
Assess response by 12/52
Assess response daily
Assess response daily
Clinical response (simple colitis index)
Bloods +/- Faecal calprotectin
Poor Response
Clinical Response
Clinical Response
Poor Response
Clinical Response
Optimise Anti-TNF (trough + Ab levels)
Add/optimize immunosuppressant
Consider a Flexible Sigmoidoscopy
Wean steroids
Commence Azathioprine
Commence oral Ciclosporin
(5mg/kg in two divided doses)
Commence Azathioprine
Co-trimoxazole 960mg/3 times a week
Prophylaxis (if on dual Rx)
Oral Ciclo = 3-6/12
Clinical Response
Colectomy
Repeat cycle x2 times if needed to optimise
Assess response after 4-8/52
No benefits switching between Ciclo and IFX if fail one therapy
(Master EA, 2008)
Continue scheduled prescribing + clinical review (Drug + Ab monitoring if loss of response)
Poor Response
Remission for UC:
Total or partial Mayo score <2 (no score >1) + steroid free
Response in UC:
Total Mayo <3
Partial Mayo <2
Assess response at 3/12
Alternative Biologic
Clinical
Trial
Surgery
Assess response by 12/52
Poor Response
Response
Colonoscopy/ sigmoidoscopy Calprotectin
Clinical Response
Alternative Biologic Therapy
Stop Ciclosporin
+ continue Aza
Remission
Partial/Incomplete Response
No Response
Consider stopping biologic + maintaining immunosuppressant
Optimise biologic +
immunosuppresent
Alternative biologic/
surgery
Partial Response = optimise therapy
Response
No response = Colectomy

3. Loss or poor response to biologic anti-TNF therapy
Pathway C
Loss or poor response to biologic anti-TNF therapy
Confirmation of IBD flare
Faceal calprotectin
Endoscopic/radiological evidence
Bloods
Exclude alternative pathology
Stricture
Cancer
Infection
IBS
Anti-TNF drug trough level
Undetectable
Anti TNF drug trough level
Detectable
Anti TNF drug antibody may be positive or negative
Anti-TNF drug antibodies
Detectable
Anti –TNF drug antibodies
Undetectable
Drug being neutralised by drug antibodies
Insufficient drug available
Check adherence
Increased drug clearance
Low drug trough & antibody low/undetectable
Low drug trough & high antibody
Trough level within or therapeutic range & loss of clinical response
Anti – TNF antibody level >10
Stop anti- TNF
Switch drug
Anti-TNF antibody level <10
Add/optimise immunosuprresant
Increase dose/frequency of anti -TNF
Improve adherence
If adherence is good
Reduce time between doses or increase drug dose
Increase drug dose/frequency/add in immunosuppression/ ??switch to alternative biologic
Consider switch to alternative biologic (in or out of class)
Switch to an alternative biologic out of class
Antibodies
The precise level of antibody significance is currently undefined.
A low level of antibody can be clinically significant if it is neutralizing the drug
An antibody level greater than 40 is unlikely to be cleared by immunosuppression or anti-TNF dose adjustment.
Following anti-TNF dose adjustment/adding in immunosuppressant
Repeat clinical review and antibody & drug trough level testing after 2-4 months
If response = continue therapy and review after 6 months
If partial response = optimise biologic therapy/immunosupression (following further drug level and antibody testing)
If no response = consider entry in to clinical trial/alternative biologic/surgery