Definitions for EPACT chapters

Mild to Low Moderate Active Luminal Crohn's Disease
High Moderate to Severe Active Luminal Crohn's Disease
Steroid-Dependent Crohn's Disease
Steroid-Refractory Crohn's Disease
Fistulizing Crohn's Disease
Fibro-stenotic Crohn's Disease
Maintenance of Medically-induced Remission of Crohn's Disease obtained by steroids
Maintenance of Medically-induced Remission of Crohn's Disease obtained by biologicals
Maintenance of Surgically-induced Remission of Crohn's Disease
Upper Gastroduodenal Crohn's Disease
Extraintestinal Manifestations of Crohn's Disease
Pregnancy and Crohn's Disease
Administration of concomittant thiopurines and infliximab therapy

Definitions for chapter "Mild to Low Moderate Active Luminal Crohn's Disease"

Assumptions:

• current episode similar to prior episodes
• current episode treated by the same doctor
• treatment of acute episode only (not introducing maintenance therapy)
• patient not on maintenance therapy, not on immunosuppressive agent
• current episode not resolved
• extensive disease, includes a colonic location (not just distal ileon disease)
• no abscesses
• no fistula
• not steroid-dependent

a) Mild luminal Crohn's Disease (CDAI > 150-220)
Mildly-active disease clinically applies to ambulatory patients able to tolerate oral alimentation, without manifestation of dehydration, toxicity (high fever, rigor, prostration), abdominal tenderness, painful mass, obstruction, or >10% weight loss [1]. Crohn's Disease is defined as quiescent when Crohn's Disease Activity Index (CDAI) is calculated to be less than 150 points [2]. (Quiescent disease = Crohn?s Disease in remission)

b) Low moderate luminal Crohn's Disease (CDAI > 220-300)
Moderately-active disease clinically applies to patients who have failed to respond to treatment for mild-moderate disease or those with more prominent symptoms of fever, significant weight-loss, abdominal pain or tenderness, intermittent nausea or vomiting (without obstructive findings), or significant anaemia [1].

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [13]

Antibiotic treatment
Metronidazole 10 to 20 mg/kg/d or Ciprofloxacine 1000-2000 mg/d or both, daily treatment with one of the following for at least 6-8 weeks with clinical improvement or healing

Budesonide treatment
Budesonide 9 mg/d for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed.

Prednisone treatment
Daily Prednisone (40-60 mg or 1-1.5 mg/kg/d) or equivalent for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after prednisone treatment was completed

Azathioprine / 6 MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Methotrexate therapy
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Infliximab up
An increase of the dose of infliximab from 5 mg/kg to 10 or 15 mg/kg

Loss of response to infliximab
Presence of symptoms or evidence of disease activity despite an increase of infliximab dosing to 10 mg/kg and a decrease in interval to 4 weeks between infliximab infusions [15].

Infliximab intolerance
Inability to tolerate infliximab was defined when acute or delayed hypersensitivity reactions (as defined by the investigator) led to discontinuation of infliximab therapy [18].

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Definitions for chapter "High moderate to Severe or fulminant luminal Crohn's Disease"

Assumptions:

• patient is very sick, very active disease
• no abcesses, or abcess treated (drained)
• no mechanical intestinal obstruction / no stenotic disease

a) Low moderate luminal Crohn's Disease (CDAI > 300-450)
Moderately-active disease clinically applies to patients who have failed to respond to treatment for mild-moderate disease or those with more prominent symptoms of fever, significant weight-loss, abdominal pain or tenderness, intermittent nausea or vomiting (without obstructive findings), or significant anaemia [1].

b) Severe luminal Crohn's Disease (CDAI > 450- 600)
Severely-active disease refers to patients with high fever and persisting symptoms (e.g. persistent vomiting, rebound tenderness, evidence of intestinal obstruction, cachexia or evidence of an abscess) despite the introduction of steroids. This definition was derived from Hanauer and Sandborn ⁹.

Limited or extensive disease

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [13]

Prednisone treatment
Daily Prednisone (40-60 mg or 1-1.5 mg/kg/d) or equivalent for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after prednisone treatment was completed.

Budesonide treatment
Budesonide 9 mg/d for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed.

High Dose Steroids
= iv or high dose peroral administration.

Fast-acting immunosupressors
Tacrolimus 0.01-0.02 mg/kg/d IV for <7 days and then an oral treatment of 0.1-0.2 mg/kg/d bid for at least 6 weeks with clinical improvement or healing [23],[24].
OR
Cyclosporine 2-4 mg /kg/d intravenous or 5-8 mg/kg/d orally, treatment for at least 2 months with clinical improvement or healing evident after 2 weeks [21],[22]. The drug should not be continued for more than 3–6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine.
OR
Mycophenolate mofetil 750 mg -2g/d or 15 mg/kg/d treatment with clinical improvement or healing [25],[26],[27].

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Immunomodulation (= Drug-induced immunosuppression state)
Patient under azathioprine, 6-mercaptopurine or methotrexate therapy at adequate doses and duration.

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Definition for chapter "Steroid-dependant Crohn's Disease (CDAI < 220)"

Complete clinical remission or improvement to mild-to-moderate disease with corticosteroid treatment (prednisone 40-60mg/day or equivalent) and relapse within 30 days after prednisone treatment was completed, or relapse with a dose reduction of prednisone resulting in the use of prednisone at doses less than or equal to 15-25 mg/day for at least 6 months [3].

Azathioprine / 6 MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Methotrexate treatment
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Immunomodulation (= Drug-induced immunosuppression state)
Patient under azathioprine, 6-mercaptopurine or methotrexate therapy at adequate doses and duration.

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Limited or extensive disease

Definitions for chapter "Fistulizing Crohn's Disease"

Documented by one or more of the following: digital rectal examination and insertion of probes into fistula tracks (gold standard), fistulography, computed tomography, MRI or endoscopic ultrasonography [5].

Assumptions:

• Any abscess have been drained before this evaluation.
• Internal (entero-enteric) and entero-cutaneous fistulas are not considered in this chapter.

The type of fistula is desribed following a complete investigation

• Low simple fistula
  Perianal fistula, without rectal involvement (below the dentate line).
• High complex fistula
  Complex CD fistula : high fistula, rectal involvement (including transphincteric and rectovaginal fistulas).
  
  

Antibiotic treatment
Metronidazole 10 to 20 mg/kg/d or Ciprofloxacine 1000-2000 mg/d or both, daily treatment with one of the following for at least 6-8 weeks with clinical improvement or healing

CysA / Tacrolimus therapy
Tacrolimus 0.01-0.02 mg/kg/d IV for <7 days and then an oral treatment of 0.1-0.2 mg/kg/d bid for at least 6 weeks with clinical improvement or healing ^11,4.

Azathioprine / 6MP therapy
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Methotrexate therapy
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Conservative Surgery
Includes : flaps, seton, glue

Non-conservative ("aggressive") surgery
Includes : proctocolectomy, diversion (stoma)

Definitions for chapter "Fibro-stenotic Crohn's Disease (= B2; Vienna Classification)"

Documented with compatible symptoms, confirmed by barium radiography or CT, without laboratory and clinical signs of inflammation and where inflammatory stenosis was excluded by a corticosteroid test (1mg/kg/d intravenous for 5-7 days) [3].

Assumption

• Balloon dilatation implies endoscopically-reachable stenosis

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [13]

Azathioprine / 6MP therapy
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Methotrexate therapy
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

Antibiotic treatment
Metronidazole 10 to 20 mg/kg/d or Ciprofloxacine 1000-2000 mg/d or both, daily treatment with one of the following for at least 6-8 weeks with clinical improvement or healing

Steroid treatment
Prednisone 40-60mg (1-1.5 mg/kg/d) or equivalent, or Budesonide 9mg/d for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed [14].

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Definitions for chapter "Maintenance of medically-induced remission of Crohn's Disease obtained by steroids"

Assumption:

• For this chapter: assume that remission was obtained with steroids.

5a) Remission (= quiescent disease) Clinical remission (CDAI <150), possibly confirmed by endoscopy, refers to patients who are asymptomatic or without inflammatory sequelae and includes patients who have responded to acute medical intervention [1].

5b) Relapses
Defined as both a CDAI >150 points and a minimum increase of the baseline CDAI score of >70 points [3]. (Relapse is a clinical definition whereas recurrence means the presence of lesions)

• Low frequency of relapses : < 1 years
• High frequency of relapses : > 1 years
  
  
  

Azathioprine / 6MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Methotrexate
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [5].

Budesonide treatment
Budesonide 9 mg/d for at least two weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed.

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Probiotic treatment
Probiotic treatment = oral bacteriotherapy = ingestion of a mixture of various "healthy bacterias" to replace endogenic pathogenous flora.

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Wait & see
Means to follow the course of the disease clinically and/or endoscopically, in absence of any maintenance therapy, at least every 6 to 12 months.

Definitions for chapter "Maintenance of medically-induced remission of Crohn's Disease obtained by biologicals"

Assumption:

• For this chapter: assume that remission was obtained with biologicals (infliximab, adalimumab, certolizumab).

5a) Remission (= quiescent disease) Clinical remission (CDAI <150), possibly confirmed by endoscopy, refers to patients who are asymptomatic or without inflammatory sequelae and includes patients who have responded to acute medical intervention [1].

5b) Relapses
Defined as both a CDAI >150 points and a minimum increase of the baseline CDAI score of >70 points [3]. (Relapse is a clinical definition whereas recurrence means the presence of lesions)

• Low frequency of relapses : < 1 years
• High frequency of relapses : > 1 years
  
  
  

Azathioprine / 6MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Methotrexate
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [5].

Budesonide treatment
Budesonide 9 mg/d for at least two weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed.

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Probiotic treatment
Probiotic treatment = oral bacteriotherapy = ingestion of a mixture of various "healthy bacterias" to replace endogenic pathogenous flora.

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Wait & see
Means to follow the course of the disease clinically and/or endoscopically, in absence of any maintenance therapy, at least every 6 to 12 months.

Definitions for chapter "Maintenance of surgically-induced remission of Crohn's Disease"

Patient's category of risk
Evaluation of flare's prognosis based on the classification of high and low risk, according to the risk factors listed in this table:

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [5].

Antibiotic treatment
Metronidazole 10 to 20 mg/kg/d or Ciprofloxacine 1000-2000 mg/d or both, daily treatment with one of the following for at least 6-8 weeks with clinical improvement or healing

Azathioprine / 6MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of these for at least 2 months with clinical improvement or healing

Methotrexate
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

Infliximab treatment
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Watch & wait
Means to follow the course of the disease clinically and/or endoscopically, in absence of any maintenance therapy, at least every 6 to 12 months[6].

Definitions for chapter "Upper Gastroduodenal Crohn's Disease"

Documented by endoscopic appearance or mucosal biopsy AND excluding severe stenosis. Two criteria for diagnosis: suggested by Nugent et al [7],[8] and considering comments from Wagtmans et al (van Hogezand, Witte et al. 2001).

1. Histological presence of non caseing granulomatous inflammation in the upper digestive tract with or without Crohn's disease elsewhere in the intestinal tract and without evidence of systemic granulomatous disorders, OR
2. Crohn's disease of the small or large bowel and radiological and /or endoscopic findings of diffuse inflammatory change in the upper digestive tract consistent with Crohn's disease.

Proton pump inhibitor treatment
Daily therapy with a PPI (e.g. omeprazole 20 mg/d, lanzoprazole 30mg/d or pantoprazole 40mg/d) for at least 6 weeks [12].

5-ASA treatment
Mesalazine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks [5].

Steroid treatment
Prednisone 40-60mg (1-1.5 mg/kg/d) or equivalent, or Budesonide 9mg/d for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed [14].

Azathioprine / 6MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

Definitions for chapter "Extraintestinal Manifestations of Crohn's Disease"

Inflammatory manifestations outside of the digestive tract related to underlying disease activity ( peripheral arthritis, erythema nodosum or aphtous ulcers, episcleritis) or independent ( pyoderma gangrenosum, uveitis, spondylarthropathy -axial arthropathy- , primary sclerosing cholangitis )[9]. Extradigestive associated diseases (gallstones, nephrolithiasis) and non disease specific complications (amyloidosis, osteoporosis, thromboembolic complication) are not included [10]. Extraintestinal side effects of Crohn’s disease therapy have to be excluded.

Methotrexate
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

Azathioprine / 6MP treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

CysA / Tacrolimus therapy
Tacrolimus 0.01-0.02 mg/kg/d IV for <7 days and then an oral treatment of 0.1-0.2 mg/kg/d bid for at least 6 weeks with clinical improvement or healing ^11,4.

Steroid treatment
Prednisone 40-60mg (1-1.5 mg/kg/d) or equivalent, or Budesonide 9mg/d for at least 2 weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed [14].

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Definitions for chapter "Pregnancy and Crohn's Disease"

• Therapeutic considerations concerning a woman with Crohn's Disease who is pregnant or contemplating pregnancy
• Includes control of Crohn's Disease activity before and during pregnancy, the effects of this treatment on fertility, as well as the safety of drugs on the embryogenesis development and maturation of the foetus and of the nursing newborn
• Early pregnancy is considered as being until the end of the first trimester
• Quiescent disease = CD in remission: asymptomatic patient, CDAI score < 150

5-ASA treatment
Mesalamine : 3.2 to 4 g/d or Sulfasalazine: 3 to 6 g in divided doses, daily treatment with one of the following for at least 2 to 4 weeks ⁵.

Antibiotic treatment
Metronidazole 10 to 20 mg/kg/d or Ciprofloxacine 1000-2000 mg/d or both, daily treatment with one of the following for at least 6-8 weeks with clinical improvement or healing

Budesonide treatment
Budesonide 9 mg/d for at least two weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after corticosteroid treatment was completed.

Prednisone treatment
Daily Prednisone (40-60 mg or 1-1.5 mg/kg/d) or equivalent for at least two weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after prednisone treatment was completed

Azathioprine treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Adalimumab therapy
Adalimumab 160 mg subcutaneously at week 0 and 80 mg at week 2 with clinical improvement or healing at week 4, then as maintenance schedule at 40 mg every other week [16],[17].

Certolizumab therapy
Certolizumab 400 mg subcutaneously at week 0, 2, 4, 8 with clinical improvement or healing, then as maintenance schedule (once every 4 weeks) [18],[19].

Natalizumab therapy
Natalizumab 300 mg (weight-based doses 3 to 4 mg/kg) intravenously every 4 weeks with clinical improvement or healing, then as maintenance schedule every 4 weeks

CysA / Tacrolimus therapy
Tacrolimus 0.01-0.02 mg/kg/d IV for <7 days and then an oral treatment of 0.1-0.2 mg/kg/d bid for at least 6 weeks with clinical improvement or healing ^11,4.

Probiotic treatment
Probiotic treatment = oral bacteriotherapy = ingestion of a mixture of various "healthy bacterias" to replace endogenic pathogenous flora.

Mycophenolate mofetil therapy
Mycophenolate mofetil 750 mg -2g/d or 15 mg/kg/d treatment with clinical improvement or healing [25],[26],[27].

Definitions for chapter "Administration of Concomittant Thiopurines and Infliximab Therapy"

Azathioprine treatment
Azathioprine 2-3 mg/kg/d or 6-Mercaptopurine 1-1.5 mg/kg/ daily treatment with one of the following for at least 2 months with clinical improvement or healing

Infliximab therapy
Infliximab 5-10 mg/kg/d treatment at week 0, 2 and 6 with clinical improvement or healing, then as maintenance therapy on a symptom-directed or a fixed (every 8 weeks) schedule. Should be given with antibody-preventive therapy (steroids premedication or effective immunosuppressive treatment).

Prednisone treatment
Daily Prednisone (40-60 mg or 1-1.5 mg/kg/d) or equivalent for at least two weeks with complete or partial clinical response and no regression of clinical symptoms 30 days after prednisone treatment was completed

Methotrexate
Methotrexate 10-25 mg/week treatment for at least 2 months with clinical improvement or healing

REFERENCES

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