Psoriatic arthritis toxicity and severity descriptors

Toxicity and severity descriptors for Disease Modifying Anti Rheumatic Drug (DMARD) treatments required to be trialled before accessing PBS-subsidised biological medicines to treat psoriatic arthritis.

Use the following toxicity and severity descriptors in conjunction with the authority application when demonstrating patient’s intolerance to DMARDs treatment:

  • ALT - alanine aminotransferase
  • AST - aspartate aminotransferase
  • BP - blood pressure
  • ECG - electrocardiogram
  • IV - intravenous
  • LV - left ventricle
  • NIH - National Institutes of Health
  • PT - Prothrombin time
  • ULN - upper limit of normal
  • WCC - white cell count.
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
ArrhythmiaSymptomatic and requiring therapy3 (or higher)
Cardiac LV functionCongestive cardiac failure responsive to treatment3 (or higher)
Fluid retentionSymptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation3 (or higher)
HypertensionRecurrent or persistent rise of > 20 mmHg diastolic BP or rise to > 150 over 90 on 2 occasions if BP previously normal2 (or higher)
Pericardial effusion or pericarditisPericarditis (pericardial rub, ECG changes or chest pain)2 (or higher)
Thrombosis or embolismRequiring anticoagulant therapy3 (or higher)
Coagulation
Prothrombin timePT > 2 x ULN3 (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 where the causative DMARD is methotrexate, 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 to intramuscular dosing
  • 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)
Weight gain or loss20% or more weight gain or loss3 (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
Ataxia (incoordination)Mild symptoms interfering with function but not interfering with activities of daily living2 (or higher)
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)
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)
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 treatment3 (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)
Proteinuria> 1.0 g per 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 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
Page last updated: 1 March 2024.
QC 41441