Crohn's disease toxicity and severity descriptors

Toxicity and severity descriptors for treatments required to be trialled before accessing PBS-subsidised biological medicines to treat Crohn's disease.

Prednisolone

Adverse eventBrief description of minimum gradeNational Institutes of Health common toxicity criteria grade
Gastrointestinal
Gastric irritation or ulcerRequiring medical management2 (or higher)
NauseaOral intake significantly reduced2 (or higher)
Vomiting2 or more episodes in 24 hours over pre-treatment2 (or higher)
Weight gain≥ 20% weight gain3 (or higher)
Cardiovascular
HypertensionRequiring therapy or more intensive therapy than previously3 (or higher)
Fluid retentionSymptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation3 (or higher)
Central nervous system 
past psychiatric history is not a contraindication
InsomniaFrequent insomnia interfering with activities of daily living3 (or higher)
Mood alterationSevere mood alteration interfering with activities of daily living3 (or higher)
Personality or behaviourDisruptive to patient or family, requiring mental health intervention3 (or higher)
RestlessnessSevere3 (or higher)
Dermatological
Acne or dermatological conditionsSevere3 (or higher)
Purpura or bruisingGeneralised or mucosal petechiae3 (or higher)
Impaired healingRequiring medical management2 (or higher)
Laboratory
HyperglycaemiaGlucose 13.9 mmol per L or higher3 (or higher)
Hypertriglyceridaemia> 5-10 x upper limit of normal3 (or higher)
Hypokalaemia< 3.0 mmol per L3 (or higher)
Endocrine
Cushingoid appearancePresent3 (or higher)
Disordered menstruationVery irregular over pre-treatment2 (or higher)
Ocular
CataractsSymptomatic visual loss requiring treatment or interfering with function3 (or higher)
GlaucomaIncrease in intraocular pressure with retinal changes2 (or higher)
Musculoskeletal
Osteoporosis or fractureSymptomatic, interfering with activities of daily living 
Avascular necrosisSymptomatic, interfering with function2 (or higher)
MyopathySymptomatic, interfering with function2 (or higher)
Miscellaneous
ImmunosuppressionSevere, requiring treatment withdrawal 
Impaired healingSymptomatic, interfering with activities of daily living 
Growth retardation  

Azathioprine

Adverse eventBrief description of minimum gradeNational Institutes of Health common toxicity criteria grade
Neoplasms
New malignancySerious malignancy present4
Gastrointestinal
NauseaOral intake significantly reduced2 (or higher)
Vomiting2 or more episodes in 24 hours over pre-treatment2 (or higher)
DiarrhoeaIncrease of more than 4 stools per day over pre-treatment, or incontinence2 (or higher)
StomatitisPainful erythema, oedema or ulcers but can eat or swallow2 (or higher)
Abdominal painSevere pain, analgesia interfering with activities of daily living3 (or higher)
PancreatitisAbdominal pain with pancreatic enzyme elevation3 (or higher)
Hepatic
Bilirubin> 1.5 x upper limit of normal2 (or higher)
Hepatic enzymes> 2.5 x upper limit of normal2(or higher)
Dermatological
RashRash with associated symptoms over less than 50% of body surface2 (or higher)
AlopeciaPronounced hair loss3 (or higher)
Pulmonary
PneumonitisX-ray changes, requiring steroids and diuretics2 (or higher)
Miscellaneous
HypersensitivityRash, drug fever >38 °C, aches, etc.2 (or higher)
Immunosuppression or atypical infectionSevere or systemic infection requiring intravenous antimicrobial treatment or hospitalisation3 (or higher)
Haematological
Leukocytes< 2 x 109 per L3 (or higher)
Haemoglobin< 80 g per L3 (or higher)
Thrombocytes< 50 x 109 per L3 (or higher)

Mercaptopurine

Adverse eventBrief description of minimum gradeNational Institutes of Health common toxicity criteria grade
Haematological
Leukocytes< 2 x 109 per L3 (or higher)
Haemoglobin< 80 g per L3 (or higher)
Thrombocytes< 50 x 109 per L3 (or higher)
Neoplasms  
New malignancySerious malignancy present4
Gastrointestinal
NauseaOral intake significantly reduced2 (or higher)
Vomiting2 or more episodes in 24 hours over pre-treatment2 (or higher)
DiarrhoeaIncrease of more than 4 stools per day over pre-treatment, or incontinence2 (or higher)
StomatitisPainful erythema, oedema or ulcers but can eat or swallow2 (or higher)
Abdominal painSevere pain, analgesia interfering with activities of daily living3 (or higher)
PancreatitisAbdominal pain with pancreatic enzyme elevation3 (or higher)
Hepatic
Bilirubin> 1.5 x upper limit of normal2 (or higher)
Hepatic enzymes> 2.5 x upper limit of normal2 (or higher)
Dermatological
RashRash with associated symptoms over less than 50% of body surface2 (or higher)
AlopeciaPronounced hair loss3 (or higher)
Pulmonary
PneumonitisX-ray changes, requiring steroids and diuretics2 (or higher)
Miscellaneous
HypersensitivityRash, drug fever >38 °C, aches, etc.2 (or higher)
Immunosuppression or atypical infectionSevere or systemic infection requiring intravenous antimicrobial treatment or hospitalisation3 (or higher)

Methotrexate

Adverse eventBrief description of minimum gradeNational Institutes of Health common toxicity criteria grade
Alimentary tract
DiarrhoeaIncrease of more than 4 stools per day over pre-treatment, or incontinence2 (or higher)
Nausea

Oral intake significantly decreased and symptoms that don't respond to at least 2 of the following:

  • reduction of the methotrexate dose
  • folinic acid or folic acid supplementation
  • switching from oral dosing to intramuscular dosing
  • splitting the methotrexate dose over 12 hours

A minimum of 3 doses of methotrexate should have been trialled

2 (or higher)
StomatitisPainful erythema, oedema or ulcers but able to eat or swallow2 (or higher)
Vomiting2 or more episodes in 24 hours over pre-treatment2 (or higher)
Blood
Haemoglobin< 80 g per L3 (or higher)
Clinical haemorrhageRequiring transfusion3 (or higher)
Leukocytes< 2 x 109 per L3 (or higher)
PhlebitisPresent2 (or higher)
Thrombocytes< 50 x109 per L3 (or higher)
Central nervous system
AtaxiaMild symptoms interfering with function but not interfering with activities of daily living2 (or higher)
HearingTinnitus or hearing loss not requiring treatment2 (or higher)
IncoordinationMild symptoms interfering with function but not interfering with activities of daily living2 (or higher)
Mood alterationModerate mood alteration interfering with function but not interfering with activities of daily living2 (or higher)
VisionSymptomatic and interfering with function but not interfering with activities of daily living3 (or higher)
Dermatological
AlopeciaPronounced hair loss2 (or higher)
RashRash with associated symptoms over less than 50% of body surface2 (or higher)
Hepatic
Bilirubin> 1.5 x upper limit of normal2 (or higher)
Elevated transaminases
  • Alanine aminotransferase and/or aspartate aminotransferase > 2.5 x upper limit of normal
    or
  • Alanine aminotransferase and/or aspartate aminotransferase > 1.5 x upper limit of normal on 3 occasions over a 3-month period
2 (or higher)
Elevated serum alkaline phosphatase2.5 x upper limit of normal2 (or higher)
Respiratory 
Pneumonitis/pulmonary infiltratesRadiographic changes requiring steroids/diuretics2 (or higher)
Pulmonary fibrosisRequiring steroids/diuretics2 (or higher)
Cough (severe)Severe cough/coughing spasm that is poorly controlled or unresponsive to treatment. Evidence of reversal on treatment withdrawal3 (or higher)
Renal
Renal impairmentCreatinine clearance <30 mL/min3 (or higher)
Other
Allergic reactionUrticaria, drug >38 °C or bronchospasm2 (or higher)
InfectionSevere, systemic infection, requiring IV antimicrobial treatment or hospitalisation3 (or higher)
Headaches (severe)Severe pain (requiring compound analgesics) where pain/analgesics severely interfere with activities of daily living3 (or higher)
Nodulosis (following introduction of methotrexate therapy)Development of multiple new nodules causing significant local pressure symptoms and distress to the patient 
Page last updated: 1 March 2024.
QC 31856