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
Assumptions:
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].
Drug Status Not / Never Given Failure Prior Successful |
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 Infliximab intolerance Adalimumab therapy Certolizumab therapy Natalizumab therapy Assumptions: a) Low moderate luminal Crohn's Disease (CDAI > 300-450)
b) Severe luminal Crohn's Disease (CDAI > 450- 600) Limited or extensive disease
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].
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 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 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 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"
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].
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.
Small bowel disease involved < 50cm |
Small bowel disease involved >= 50cm |
Limited colonic disease (<= 2 segments) |
Pancolitis +/- rectitis |
/ |
Risk of loss of critical bowel segments by surgery |
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy 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].
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 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 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)"
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Limited or extensive disease
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 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 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
Small bowel disease involved < 50cm |
Small bowel disease involved >= 50cm |
Limited colonic disease (<= 2 segments) |
Pancolitis +/- rectitis |
/ |
Risk of loss of critical bowel segments by surgery |
Corticosteroid-refractory Crohn's Disease is defined as failing to respond to treatment with prednisone, assuming adequate doses (up to 1 mg/kg) within a 4-week time-frame (relapse to moderate-to-severe disease) [4].
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Limited or extensive disease
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 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 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
Small bowel disease involved < 50cm |
Small bowel disease involved >= 50cm |
Limited colonic disease (<= 2 segments) |
Pancolitis +/- rectitis |
/ |
Risk of loss of critical bowel segments by surgery |
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:
The type of fistula is desribed following a complete investigation
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Conservative Surgery Non-conservative ("aggressive") surgery
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 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 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
Includes : flaps, seton, glue
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
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Assumption: 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
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 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 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"
Maintenance of medically-induced remission, without relapse [3].
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)
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Wait & see Assumption: 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
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 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 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
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"
Maintenance of medically-induced remission, without relapse [3].
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)
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Wait & see Patient's category of risk
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 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 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
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"
Preventing relapse in patients who have undergone surgical resection without gross evidence of residual disease 9
Evaluation of flare's prognosis based on the classification of high and low risk, according to the risk factors listed in this table:
=>2 |
Prior operations for Crohn's Disease |
<2 |
Female |
Gender |
Male |
YES |
Previous resection > 1 m |
NO |
YES |
Smoking |
NO |
YES |
Ileocolonic disease |
NO |
YES |
Perianal disease |
NO |
YES |
Severe lesion at endoscopy (at about 6-12 months) |
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy Watch & wait 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).
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 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 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
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"
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy 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.
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 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 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"
Drug Status Not / Never Given Failure Prior Successful |
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 Important Note: for this chapter, the term appropriateness applies to drug safety in pregnancy :
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"
1 = very unsafe, 9 = extremely safe ·
Drug Status Not / Never Given Failure Prior Successful |
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 Certolizumab therapy Natalizumab therapy CysA / Tacrolimus therapy Probiotic treatment Mycophenolate mofetil therapy Azathioprine treatment Infliximab therapy Prednisone treatment Methotrexate REFERENCES
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 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 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
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 = oral bacteriotherapy = ingestion of a mixture of various "healthy bacterias" to replace endogenic pathogenous flora.
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 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 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).
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 10-25 mg/week treatment for at least 2 months with clinical improvement or healing