Pathway A Anti-TNFs in - PowerPoint Presentation

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Pathway A

Anti-TNFs in Crohn’s Disease used for:Severe active CD: HBI = >8 CDAI = >300Inadequate response for tolerance of contraindication to conventional therapiesChronic active CD with failure to control with immunosuppressionConsider 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.

Crohn’s Disease Biologic Pathway

Severe active Crohn’s (TA 187, TA 456)Failure or intolerance of immunosuppressionAdalimumab SC , Infliximab IV, ustekinumab

Active Fistulating (TA 187, TA 352, TA 456)Infliximab = 1st LineConsider 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

Continue scheduled prescribing + clinical review for response

Reassess response at 12/12 = NICE REVIEW

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.

Assess response after 8 - 16/52eg. repeat drug and antibody levels

Clinical response (HBI)

Faecal

calprotectin

Colonoscopy/Radiology (Small Bowel)

Poor Response

Clinical Trial

Alternative biologic

Vedolizumab

(

TA 352

)

Surgery

Pathway B

Ulcerative Colitis Biologics PathwayNICE CG 166Moderately to severe active UCAcute 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

Assess response by 12/52

Assess response by 12/52

Poor Response

Clinical Response

Clinical response (simple colitis index)

Bloods +/- Faecal

calprotectin

Optimise Anti-TNF (trough +

A

b

levels)Add/optimize immunosuppressantConsider a Flexible

Sigmoidoscopy

Assess response after 4-8/52Poor Response

Surgery

Clinical Trial

Alternative Biologic

Clinical Response

Continue scheduled prescribing + clinical review (Drug +

A

b

monitoring if loss of response)

Assess response by 12/52

Remission

Partial/Incomplete Response

No Response

Consider stopping biologic + maintaining immunosuppressant

Optimise biologic +immunosuppresent

Alternative biologic/ surgery

Repeat cycle x2 times if needed to optimise

Colonoscopy/

sigmoidoscopy

Calprotectin

Clinical Response

Assess response daily

Assess response daily

Clinical Response

Poor Response

Clinical Response

Colectomy

Assess response at 3/12

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

Poor Response

Response

Stop

Ciclosporin

+ continue

Aza

Alternative Biologic Therapy

Response

Partial Response = optimise therapy

No response = Colectomy

Wean steroids

Commence Azathioprine

Remission for UC:

Total or partial Mayo score <2 (no score >1) + steroid free

Response in UC:

Total Mayo <3

Partial Mayo <2

No benefits switching between

Ciclo

and IFX if fail one therapy

(Master EA, 2008)

Consider giving second dose at week 1 if patient has high CRP and low serum albumin

Pathway C

Antibodies The precise level of antibody significance is currently undefined. A low level of antibody can be clinically significant if it is neutralizing the drugAn antibody level greater than 40 is unlikely to be cleared by immunosuppression or anti-TNF dose adjustment.Following anti-TNF dose adjustment/adding in immunosuppressantRepeat clinical review and antibody & drug trough level testing after 2-4 monthsIf response = continue therapy and review after 6 monthsIf partial response = optimise biologic therapy/immunosupression (following further drug level and antibody testing)If no response = consider entry in to clinical trial/alternative biologic/surgeryLoss or poor response to biologic anti-TNF therapyAnti-TNF drug trough level

Undetectable

Anti TNF drug trough levelDetectable Confirmation of IBD flareFaceal calprotectinEndoscopic/radiological evidence

Bloods

Anti –TNF drug antibodies

Undetectable

Anti – TNF antibody level >10

Stop anti- TNF

Switch drug

Anti-TNF antibody level <10Add/optimise immunosuprresant

Increase dose/frequency of anti -TNF

Insufficient drug available

Check adherence

Increased drug clearance

Anti TNF drug antibody may be positive or negative

Anti-TNF drug antibodies

D

etectable

Drug being neutralised by drug antibodies

Improve adherence

If adherence is good

Reduce time between doses or increase drug doseExclude alternative pathology

StrictureCancerInfectionIBS

Low drug trough & antibody low/undetectable

Increase drug dose/frequency/add in immunosuppression/

??switch to alternative biologic

Low drug trough & high antibody

Consider switch to alternative biologic (in or out of class)

Trough level within or therapeutic range & loss of clinical response

Switch to an alternative biologic out of class