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 16-20 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 8 - 16/52 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.

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

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