Ulcerative colitis toxicity and severity descriptors

Toxicity criteria and severity descriptors for treatments required to be trialled before accessing PBS-subsidised biological medicines to treat ulcerative colitis.

ADL - activities of daily living
NIH - National Institutes of Health
LLN - lower limit of normal
ULN - upper limit of normal

Prednisolone

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Gastro-intestinal
Gastric irritation/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 not a contraindication
InsomniaFrequent insomnia interfering with ADL3 (or higher)
Mood alterationSevere mood alteration interfering with ADL3 (or higher)
Personality/behaviouralDisruptive to patient/family, requiring mental health intervention3 (or higher)
RestlessnessSevere3 (or higher)
Dermatological
Acne/dermatological conditionsSevere3 (or higher)
Purpura/bruisingGeneralised or mucosal petechiae3 (or higher)
Impaired healingRequiring medical management2 (or higher)
Laboratory
HyperglycaemiaGlucose 13.9 mmol/L or higher3 (or higher)
Hypertriglyceridemia> 5-10 x ULN3 (or higher)
Hypokalaemia< 3.0 mmol/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/fractureSymptomatic, interfering with ADL 
Avascular necrosisSymptomatic, interfering with function2 (or higher)
MyopathySymptomatic, interfering with function2 (or higher)
Miscellaneous
Immuno-suppressionSevere, requiring treatment withdrawal3 (or higher)
Impaired healingSymptomatic, interfering with ADL 
Growth retardation  

Azathioprine

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Haematological
Leucocytes< 2 x 109 / L3 (or higher)
Haemoglobin< 80 g/L3 (or higher)
Thrombocytes< 50 x 109 / L3 (or higher)
Neoplasms
New malignancySerious malignancy present4
Gastro-intestinal
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/swallow2 (or higher)
Abdominal painSevere pain/analgesia interfering with ADL3 (or higher)
PancreatitisAbdominal pain with pancreatic enzyme elevation3 (or higher)
Hepatic  
Bilirubin> 1.5 x ULN2 (or higher)
Hepatic enzymes> 2.5 x ULN2(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 > 380, aches etc.2 (or higher)
Immuno-suppression/atypical infectionSevere/systemic infection requiring IV antibiotic/antifungal treatment or hospitalisation3 (or higher)

Mercaptopurine

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Haematological
Leucocytes< 2 x 109 / L3 (or higher)
Haemoglobin< 80 g/ L3 (or higher)
Thrombocytes< 50 x 109 / L3 (or higher)
Gastro-intestinal   
NauseaOral intake significantly reduced2 (or higher)
Vomiting2 or more episodes in 24 hours over pre-treatment2 (or higher)
AnorexiaOral intake significantly reduced2 (or higher)
Stomatitis (oral ulcers etc.)Painful erythema, oedema or ulcers but can eat/swallow2 (or higher)
PancreatitisAbdominal pain with pancreatic enzyme elevation3 (or higher)
Hepatic
Bilirubin> 1.5 x ULN2 (or higher)
Hepatic enzymes> 2.5 x ULN2 (or higher)
Dermatological
RashRash with associated symptoms over less than 50% of body surface2 (or higher)
AlopeciaPronounced hair loss3 (or higher)
Neoplasia
Secondary malignancy (e.g. leukaemia)Present4
Miscellaneous
HypersensitivityRash, drug fever > 38°C, arthralgia etc.2 (or higher)
Joint painModerate pain/analgesics, significantly interferes with function2 (or higher)

5-aminosalicylates

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Blood / Bone Marrow
AnaemiaHaemoglobin < 80 g/L3 (or higher)
LeukopeniaTotal WCC < 3 x 109 / L2 (or higher)
ThrombocytopeniaPlatelets < 50 x 109 / L3 (or higher)
NeutropeniaTotal neutrophils < 1.0 x 109 / L3 (or higher)
Dermatology / Skin
AlopeciaPronounced hair loss2 (or higher)
Rash / desquamationScattered macular or papular eruption or erythema with pruritus or other associated symptoms covering < 50% of body surface or localised desquamation or other lesions covering < 50% of body2 (or higher)
Gastrointestinal
DiarrhoeaIncrease of 4-6 stools/day over pre-treatment2 (or higher)
NauseaOral intake significantly decreased2 (or higher)
PancreatitisAbdominal pain with pancreatic enzyme elevation3 (or higher)
StomatitisPainful erythema, oedema or ulcers but able to eat or swallow2 (or higher)
Vomiting2 or more episodes per 24 hours over pre-treatment2 (or higher)
Hepatic
Bilirubin> 1.5 x ULN2 (or higher)
TransaminasesALT and/or AST > 2.5 x ULN or ALT and/or AST > 1.5 x ULN on three occasions over a 3-month period2 (or higher)
^Serum alkaline phosphatase2.5 x ULN2 (or higher)
Neurology / Senses
Headaches (severe)Severe pain: pain or analgesics severely interfere with activities of daily living3 (or higher)
HearingTinnitus or hearing loss not requiring hearing aid or treatment2 (or higher)
Mood alterationModerate mood alteration interfering with function but not interfering with activities of daily living2 (or higher)
Neuropathy - SensoryObjective sensory loss or paraesthesia interfering with function but not interfering with activities of daily living2 (or higher)
Seizure(s)Seizures in which consciousness is altered3 (or higher)
Pulmonary 
Cough (severe)Severe cough or coughing spasm, poor control or unresponsive to treatment. Evidence of reversal on cessation of treatment.3 (or higher)
Pneumonitis/pulmonary infiltratesRadiographic changes, Respiratory Function Test abnormalities and requiring steroids or diuretics2 (or higher)
Renal
HaematuriaMacroscopic (or dipstick +++) confirmed on 2 separate occasions2 (or higher)
Proteinuria> 1.0g/24 hours, elevated urine protein/creatinine ratios, (dipstick protein ++ or greater), confirmed on 2 separate occasions2 (or higher)
Renal impairmentCreatinine > 1.5 ULN or creatinine clearance < 30 mL/min2 (or higher)
Other 
Allergic reactionUrticaria, drug fever > 38°C and / or bronchospasm2 (or higher)
Fever (in the absence of neutropenia)Body temp > 39°C (oral or tympanic)2 (or higher)
Page last updated: 28 March 2024.
QC 31936