Medically-induced remission

Medically-induced remission of Crohn's disease

Avoid risk factors associated with relapse:

  • Stop smoking (refer to smoking cessation service)
  • Avoid infectious gastroenteritis; provide dietary advice and nutritional support
  • Reduce “stress”: empower patients and consider need for psychological support
  • Ensure compliance with medical therapy
  • Optimise dose and type of medical therapy
  • Avoid NSAID use

Also prevent associated disease

Reduce risk factors & prevent associated disease

Anti-TNF
induced remission

  • Daily prednisolone >/=10mg (Budesonide >/= 3mg) beyond 3/12
Steroid-dependent
remission

Steroid-induced
remission

Spontaneous
remission

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]

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]

Continue anti-TNF

 
 

ECCO statement 6A (CD 2016)

After the first presentation if remission has been achieved with systemic steroids, a thiopurine [EL1] or methotrexate [EL3] should be considered. No maintenance treatment is an option for some patients [EL5]

Further information

  • 5-ASA are not recommended, providing little benefit (39.1% vs. 32.5%; NNT = 16). One systematic review suggests pH7-dependent mesalazine (e.g. Asacol) may be superior (NNT = 5)
  • Evidence for effectiveness of antibiotics is lacking
  • Corticosteroids not effective. 6 mg Budesonide may delay relapse but is ineffective when assessed after 12 months
No treatment

ECCO statement 6D (CD 2016)

Immunosupressive naïve patients who are dependent on corticosteroids should be treated with a thiopurine [EL1] or methotrexate [EL2] or anti-TNF based strategy [EL1]. Surgical options should also be discussed [EL4]

Further information

  • Immunomodulators (thiopurines and methotrexate) are steroid-sparring agents
  • Corticosteroids are not recommended for maintenance of remission. However, switching steroid dependent patients with ileo-caecal disease to Budesonide reduces side-effects, and relapse rates are less than switching to placebo (32% cf. 65% at 13 weeks). Ultimately, aim to avoid any use of steroids
Immunomodulator,
anti-TNF or methotrexate

ECCO statement 6A (CD 2016)

After the first presentation if remission has been achieved with systemic steroids, a thiopurine [EL1] or methotrexate [EL3] should be considered. No maintenance treatment is an option for some patients [EL5]

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]

ECCO statement 6C (CD 2016)

For patients with extensive disease, thiopurines are recommended for maintenance of remission [EL1]. In patients with aggressive/severe disease course or poor prognostic factors, an anti-TNF-based strategy should be considered [EL5]

Immunomodulator,
anti-TNF or methotrexate

 

  • Anti-TNF is more effective when provided early in the disease course
Poor prognostic factors

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

  • Steroids should no longer be required after 4/12 immunomodulator therapy
  • Steroid-dependence defined as daily prednisolone >/=10mg (Budesonide >/= 3mg) beyond 3/12
Steroid-dependent

ECCO statement 6K (CD 2016)

Treatment with thiopurines is associated with an increased risk of lymphoma [EL1], non melanoma skin cancers [EL3], and cervical dysplasia [EL3]. Anti-TNF agents increase the risk of melanomas [EL3]. There is currently insufficient data to suggest that anti-TNF agents alone increase the risk of lymphoproliferative disorders or solid tumors. In contrast, their combination with thiopurines significantly increases the risk of lymphoproliferative disorders [EL3]. However, the absolute rates of these malignancies remain low and risks should always be balanced carefully against the substantial benefits associated with these treatments and discussed with the patient [EL5]

Further information

  • Reassess between 3 & 12 months, dependent on course and extent of disease, with biomarkers; with facility for urgent review if symptoms recur
  • Consider objective assessments with endoscopy and/or radiology at or after 1 year
  • Ensure treatments optimized (correct therapy, correct dose, and compliance)
Regular reassessment

 

Consider addition anti-TNF

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]

ECCO statement 6E (CD 2016)

Patients receiving thiopurines who relapse should be evaluated for adherence to therapy, and objective signs of inflammation [EL5]. Dose optimisation may improve response rates [EL4]. Where appropriate, therapy should be changed to methotrexate [EL2] or anti-TNF therapy [EL1]. Surgery should always be considered as an option in localised disease [EL4]

Further information

  • Confirm active disease (consider need to re-evaluate extent). Treatment depends on duration of remission, concurrent therapy, adherence to therapy and patient preference
  • Relapse defined as CDAI>150 (HBI>4), with increase in CDAI >70-100 (increase in HBI >/= 3 points)
  • Exclude infection as a precipitant for relapse
Relapse

  • Remission for at least 1 year, with normal blood parameters, low faecal calprotectin, and healed mucosa
  • Healed mucosa usually represents a low CD-SES, without visible ulceration
Long term, deep remission

  • Ciclosporin - two negative placebo controlled trials assessing induction and maintainance of remission
  • Mycophenalate, tacrolimus, cyclophosphamide – no controlled studies to determine effect
  • Efficacy for Omega-3 fatty acids to maintain remission is controversial. The heterogeneous trial results do not support their use.
  • Partial provision or supplementation with an elemental diet may be effective to help maintain remission, although the two published studies are insufficient to determine this
  • There is no evidence that probiotics (E. coli Nissle, S. boulardii, Lactobacillus GG) assist maintenance of CD remission
  • Only one study of cytapheresis for maintenance of CD in remission has been published, and showed no effect. Peripheral blood stem cell transplantation is an exciting development. Randomised trials are ongoing

Unsubstantiated therapies

 

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]

Consider stopping therapy

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