Anti-TNF therapy

Anti-TNF Therapy

ECCO statement 5I (CD 2016)

Patients with objective evidence of active disease refractory to corticosteroids should be treated with an anti-TNF based strategy [EL1], although surgical options should also be considered and discussed at an early stage [EL5]

Further information

  • Severe disease
  • Steroid-refractory disease
  • Likelihood severe disease e.g. extensive small bowel disease; perianal disease
  • Avoid side effects of alternative treatment (steroids; surgery)
  • Lack of efficacy/contraindication/intolerance of classical immunomodulator
Clarify reasons for treatment

Initiating anti-TNF therapy

  • Reasons for Rx
    • Heal active disease
    • Reduce disease progression
    • Provide treatment safely, as per protocol
    • Prevent post-operative recurrence in high risk individuals
Define treatment objectives

 

Ideally vaccinate prior to biologic therapy

 

ECCO statement 5J (CD 2016)

All currently available anti-TNF therapies appear to have similar efficacy in luminal Crohn’s disease and similar adverse-event profiles, so the choice depends on availability, route of delivery, patient preference and cost [EL5]

Further information

Provide treatment information

Therapies in development include:

  • anti-integrins (Natalizumab (anti-α4; not available in Europe))
  • Vedolizumab (anti-α4β7) and Etrolizumab (anti-β7))
  • interleukin inhibitors (Ustekinumab (anti-IL12 p40), Fontolizumab (anti-IFNγ))
  • haematopoetic cytokines (Sargramostrim, Gm-CSF)

Some patients may require surgery

Describe alternative treatment e.g. trial therapies

  • 5mg/kg Infliximab is given IV at 0, 2 and 6 weeks
  • Azathioprine is usually given with Infliximab to enhance results (some centres use methotrexate)
Infliximab + immunomodulator induction

 

  • 160 mg Adalimumab (four pens) is given SC at week 0, 80 mg at week 2, then 40 mg EOW
  • Azathioprine can be given with Adalimumab, although the evidence for benefit is indirect (some centres prefer methotrexate)
Adalimumab +/- immunomodulator induction

ECCO statement 5K (CD 2016)

Particular care should be taken to consider serious infections as a complication of immunosuppressive therapy, including anti-TNF [EL3]

Further information

  • Assess response at 12/52 using predefined objective criteria
  • Always consider serious infection as a complication of immunosuppressive therapy
Assess primary response

No response

 

  • Response to anti-TNF determined by improvement in symptoms and bio-markers, supplemented with disease location specific imaging /endoscopy if required
  • Reassessment usually completed within 2 months of therapy change. Disease indices enable objective assessment
  • Remission defined as CDAI<150, equivalent to Harvey-Bradshaw </= 4 points
Remission or response

  • Treat primary non-responders to anti-TNF with alternative class of agent e.g. vedolizumab
  • Some patients may require surgery
  • Ensure immunomodulator therapy optimised
Alternative class of agent;
consider surgery

 

ECCO statement 6F (CD 2016)

If remission has been achieved with the combination of anti-TNF therapy and thiopurines in treatment naïve patients, maintenance with the same regimen is recommended [EL 1]. Thiopurines may be an option as monotherapy in selected patients who have achieved sustained remission on combination therapy [EL3]. If remission has been achieved with anti-TNF monotherapy, maintenance with anti-TNF monotherapy is appropriate [EL1]. Maintenance treatment with vedolizumab is appropriate in patients achieving remission with vedolizumab [EL1]

Further information

  • 5 mg/kg Infliximab IV is administered every 8 weeks
  • 40 mg Adalimumab SC is administered EOW (usually following home delivery)
Maintenance treatment

 

ECCO statement 5K (CD 2016)

Particular care should be taken to consider serious infections as a complication of immunosuppressive therapy, including anti-TNF [EL3]

Further information

  • Reassess predefined objective criteria ≈ four-monthly (e.g. initially 30 and 46 weeks after starting anti-TNF) or on request, with radiology and/or endoscopy & histology as appropriate if relapse
  • Some centres use “virtual biologic clinics” to ensure standardised, optimal care
  • Consider stopping immunomodulator at 30 weeks if sustained remission
  • Review management of medically induced remission algorithm
Regular reassessment

 
 

  • Relapse defined as CDAI>150 (HBI>4), with increase in CDAI >70-100 (increase in HBI >/= 3 points)
Relapse

  • Response to anti-TNF determined by improvement in symptoms and bio-markers, supplemented with disease location specific imaging /endoscopy if required
  • Reassessment usually completed within 2 months of therapy change. Disease indices enable objective assessment
  • Remission defined as CDAI<150, equivalent to Harvey-Bradshaw </= 4 points
Remission or response

 

ECCO statement 6B (CD 2016)

If a patient has a relapse, escalation of the maintenance treatment can be considered to prevent disease progression [EL2]. Steroids should not be used to maintain remission [EL1]. Surgery should always be considered as an option in localized disease [EL4]

Further information

  • Optimise immunomodulator
  • Optimise anti-TNF (consider need to shorten dose interval)
  • Consider surgery or trial therapies with persistent disease
  • Short course of steroids can be used to induce remission
Optimise medical therapy

ECCO statement 6G (CD 2016)

For patients in long term remission on thiopurine maintenance therapy, cessation of treatment may be considered in the absence of objective signs of inflammation [EL2]. No recommendation can be given for the duration of treatment with methotrexate. Prolonged use of anti-TNF agents may be considered if needed [EL3]

Further information

  • Consider annual objective as well as surrogate measures of mucosal healing (endoscopy and histology and/or radiology)
  • Consider withdrawal of therapy in those in deep remission
Regular assessment

 

  • Relapse defined as CDAI>150 (HBI>4), with increase in CDAI >70-100 (increase in HBI >/= 3 points)
Ongoing relapse

  • Remission for at least 1 year, with normal blood parameters, low faecal calprotectin, and healed mucosa
Prolonged anti-TNF remission

  • 5mg/kg Infliximab is given IV at 0, 2 and 6 weeks
  • Azathioprine is usually given with Infliximab to enhance results (some centres use methotrexate)
  • 160 mg Adalimumab (four pens) is given SC at week 0, 80 mg at week 2, then 40 mg EOW
  • Azathioprine can be given with Adalimumab, although the evidence for benefit is indirect (some centres prefer methotrexate)
Induction therapy with alternative anti-TNF

Therapies in development include:

  • anti-integrins (Natalizumab (anti-α4; not available in Europe))
  • Vedolizumab (anti-α4β7) and Etrolizumab (anti-β7))
  • interleukin inhibitors (Ustekinumab (anti-IL12 p40), Fontolizumab (anti-IFNγ))
  • haematopoetic cytokines (Sargramostrim, Gm-CSF)

Some patients may require surgery

Trial therapies, or surgery

Consider stopping anti-TNF with deep luminal remission

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