Systemic lupus erythematosus toxicity and severity descriptors

Toxicity and severity descriptors for treatments required to be trialled before accessing PBS-subsidised biological medicines to treat systemic lupus erythematosus.

ALT - alanine aminotransferase
AST - aspartate aminotransferase
BP - blood pressure
ECG - electrocardiogram
IV - intravenous
NIH - National Institutes of Health
ULN - upper limit of normal
WCC - white cell count

Prednisolone

Adverse eventBrief description of minimum gradeNIH 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  

Hydroxychloroquine

Only valid for adult patients.

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Blood or bone marrow
AnaemiaHaemoglobin < 80 g per L3 (or higher)
LeukopeniaTotal WCC < 3 x 109 per L2 (or higher)
ThrombocytopeniaPlatelets < 50 x 109 per L3 (or higher)
NeutropeniaTotal neutrophils < 1.0 x 109 per L3 (or higher)
Dermatology or skin
AlopeciaPronounced hair loss2 (or higher)
Rash or desquamationScattered macular or papular eruption or erythema with pruritis 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 per day over pre-treatment2 (or higher)
NauseaOral intake significantly decreased2 (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 or AST > 2.5 x ULN or ALT or AST > 1.5 x ULN on 3 occasions over a 3-month period2 (or higher)
Serum alkaline phosphatase2.5 x ULN2 (or higher)
Musculoskeletal
Muscle weaknessSymptomatic and interfering with function2 (or higher)
Neurology or 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)
Neuropathy - motorObjective weakness interfering with function but not interfering with activities of daily living2 (or higher)
Seizure(s)Seizures in which consciousness is altered3 (or higher)
VisionSymptomatic and interfering with function but not interfering with activities of daily living2 (or higher)
Vision - cornea or retinaSymptomatic corneal or retinal changes present1 (or higher)
Other
Allergic reactionUrticaria, drug fever > 38 °C or bronchospasm2 (or higher)

Methotrexate

Only valid for adult patients.

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Blood or bone marrow
AnaemiaHaemoglobin < 80 g per L3 (or higher)
LeukopeniaTotal WCC < 3 x 109 per L2 (or higher)
ThrombocytopeniaPlatelets < 50 x 109 per L3 (or higher)
NeutropeniaTotal neutrophils < 1.0 x 109 per L3 (or higher)
Cardiovascular
Pericardial effusion or pericarditisPericarditis (pericardial rub, ECG changes or chest pain)2 (or higher)
Thrombosis or embolismRequiring anticoagulant therapy3 (or higher)
Dermatology or skin
AlopeciaPronounced hair loss2 (or higher)
Rash or desquamationScattered macular or papular eruption or erythema with pruritis 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 per day over pre-treatment2 (or higher)
Nausea

Oral intake significantly decreased, and symptoms don't improve with at least 2 of the following measures:

  1. reduction of the methotrexate dose
  2. folinic acid or folic acid supplementation
  3. switching from oral to intramuscular dosing
  4. dividing the methotrexate dose over 12 hours

A minimum of 3 doses of methotrexate should have been trialled

2 (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 or AST > 2.5 x ULN or ALT or AST > 1.5 x ULN on 3 occasions over a 3-month period2 (or higher)
Serum alkaline phosphatase2.5 x ULN2 (or higher)
Musculoskeletal
Osteonecrosis
(avascular necrosis)
Symptomatic and interfering with function2 (or higher)
OsteoporosisSymptomatic and requiring treatment3 (or higher)
Neurology or senses
Decreased level of consciousnessSomnolence or sedation interfering with function but not interfering with activities of daily living2 (or higher)
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)
Seizure(s)Seizures in which consciousness is altered3 (or higher)
VisionSymptomatic and interfering with function but not interfering with activities of daily living2 (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 or pulmonary infiltratesRadiographic changes, respiratory function test abnormalities and requiring steroids or diuretics2 (or higher)
Pulmonary fibrosisRespiratory function test abnormalities and requiring steroids or diuretics2 (or higher)
Pulmonary symptoms - new or worsening (probable drug-induced pneumonitis)Development of syndrome consistent with drug-induced pneumonitis (for example, cough, dyspnoea, fever, hypoxaemia) with lung infiltrates on imaging
(refer Searles McKendry criteria)
 
Renal
HaematuriaMacroscopic (or dipstick +++) confirmed on 2 separate occasions2 (or higher)
Renal impairmentCreatinine > 1.5 ULN or creatinine clearance < 30 mL per min2 (or higher)
Other
Allergic reactionUrticaria, drug fever > 38 °C or bronchospasm2 (or higher)
Fatigue, malaiseSevere, loss of ability to perform some activities3 (or higher)
Fever (in the absence of neutropenia)Body temp > 39 °C (oral or tympanic)2 (or higher)
InfectionSevere, systemic infection, requiring IV antimicrobial treatment or hospitalisation3 (or higher)
Nodulosis (following introduction of methotrexate therapy)Development of multiple new nodules causing significant local pressure symptoms and distress to patient 
Secondary malignancySecondary malignancy present4

Azathioprine

Only valid for adult patients.

Adverse eventBrief description of minimum gradeNIH common toxicity criteria grade
Blood or bone marrow
AnaemiaHaemoglobin < 80 g per L3 (or higher)
LeukopeniaTotal WCC < 3 x 109 per L2 (or higher)
ThrombocytopeniaPlatelets < 50 x 109 per L3 (or higher)
NeutropeniaTotal neutrophils < 1.0 x 109 per L3 (or higher)
Dermatology or skin
AlopeciaPronounced hair loss2 (or higher)
Rash or desquamationScattered macular or papular eruption or erythema with pruritis 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 per 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 or AST > 2.5 x ULN or ALT or AST > 1.5 x ULN on 3 occasions over a 3-month period2 (or higher)
Ç Serum alkaline phosphatase2.5 x ULN2 (or higher)
Neurology or senses
Headaches (severe)Severe pain; pain or analgesics severely interfere with activities of daily living3 (or higher)
Pulmonary
Pneumonitis or pulmonary infiltratesRadiographic changes, respiratory function test abnormalities and requiring steroids or diuretics2 (or higher)
Other
Allergic reactionUrticaria, drug fever > 38 °C or bronchospasm2 (or higher)
Fatigue, malaiseSevere, loss of ability to perform some activities3 (or higher)
Fever (in the absence of neutropenia)Body temp > 39 °C (oral or tympanic)2 (or higher)
InfectionSevere, systemic infection, requiring IV antimicrobial treatment or hospitalisation3 (or higher)
Secondary malignancySecondary malignancy present4

Mycophenolate

Adverse eventBrief description of minimum gradeNIH 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)
DiarrhoeaIncrease of more than 4 stools per day over pre-treatment, or incontinence2 (or higher)
Central nervous system
Altered mental statusConfusion, memory impairment, lethargy or somnolence causing inability to perform usual social and functional activities3 (or higher)
DizzinessModerate unsteadiness; limiting activities of daily living2 (or higher)
TremorModerate symptoms; limiting activities of daily living2 (or higher)
InsomniaFrequent insomnia interfering with activities of daily living3 (or higher)
Dermatological
InfectionOral intervention indicated (e.g. antibiotic, antifungal, antiviral)2 (or higher)
RashRash with associated symptoms over less than 50% of body surface2 (or higher)
Blood or bone marrow
AnaemiaHaemoglobin < 80 g per L3 (or higher)
LeukopeniaTotal WCC < 3 x 109 per L2 (or higher)
ThrombocytopeniaPlatelets < 50 x 109 per L3 (or higher)
Pulmonary
InfectionOral intervention indicated (e.g. antibiotic, antifungal, antiviral)2 (or higher)
Body as a whole
SepsisLife-threatening consequences4
InfectionOral intervention indicated (e.g. antibiotic, antifungal, antiviral)2 (or higher)
HeadacheModerate pain; limiting activities of daily living2 (or higher)
FeverBody temp > 39 °C (oral or tympanic)2 (or higher)
Abdominal painSevere pain, analgesia interfering with activities of daily living3 (or higher)
NeoplasmNew malignancy present4
Page last updated: 1 July 2024.
QC 74345