Severe chronic plaque psoriasis toxicity and severity descriptors

Toxicity and severity descriptors for treatments required to be trialled before accessing PBS-subsidised biological medicines to treat severe chronic plaque psoriasis in adults.

Acitretin

At least 0.4mg/kg/day

Adverse eventBrief description of minimum grade of toxicityNational Institutes of Health common toxicity criteria grade
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 3 occasions over a 3-month period2 (or higher)
Serum alkaline phosphatase2.5 x ULN2 (or higher)
Use contraindicated in those with pre-existing significant renal diseaseCreatinine > 1.5 ULN2 (or higher)
Retinoic acid syndromeSymptoms of a degree to indicate steroid use2 (or higher)
Pseudotumour cerebriHeadache, nausea and vomiting associated with raised intracranial pressure 
NauseaOral intake significantly decreased2 (or higher)
Skin peelingDevelopment of fissures on the palms and soles which cause sufficient discomfort and pain to prevent normal day-to-day duties, and which haven't responded to regular and liberal applications of a moisturising agent 
Skin burningSufficient to disturb activities of daily living and to disturb the normal sleep pattern 

Cyclosporin

At least 2 mg/kg/day

Adverse eventBrief description of minimum grade of toxicityNational Institutes of Health
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)
Cardiovascular
HypertensionRecurrent/persistent rise of > 20 mmHg diastolic BP or rise to > 150/90 on 2 occasions if BP previously normal2 (or higher)
Fluid retentionSymptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation3 (or higher)
Dermatology/skin
Rash/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/day over pre-treatment2 (or higher)
NauseaOral intake significantly decreased2 (or higher)
PancreatitisAbdominal pain with pancreatic enzyme elevation3 (or higher)
Vomiting2 or more episodes/24 hours over pre-treatment2 (or higher)
Weight gain/loss20% or more weight gain or loss3 (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)
g Serum alkaline phosphatase2.5 x ULN2 (or higher)
Musculoskeletal
Muscle weaknessSymptomatic and interfering with function2 (or higher)
Neurology/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 that 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)
Renal
HaematuriaMacroscopic (or dipstick +++) confirmed on two 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 < 30mL/min2 (or higher)
Other
Allergic reactionUrticaria, drug fever > 38°C and/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)
HyperkalaemiaPotassium > 6 mmol/L3 (or higher)
InfectionSevere, systemic infection, requiring IV antimicrobial treatment or hospitalisation3 (or higher)
Secondary malignancySecondary malignancy present4

Methotrexate

At least 10 mg weekly

Adverse eventBrief description of minimum grade of toxicityNational Institutes of Health
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)
Cardiovascular
Pericardial effusion/pericarditisPericarditis (pericardial rub, ECG changes or chest pain)2 (or higher)
Thrombosis/embolismRequiring anticoagulant therapy3 (or higher)
Dermatology/skin
AlopeciaPronounced hair loss2 (or higher)
Rash/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/day over pre-treatment2 (or higher)
Nausea

Oral intake significantly decreased, and symptoms do not improve with at least 2 of the following measures:

  1. reduction of the methotrexate dose
  2. folinic acid/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/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)
g Serum alkaline phosphatase2.5 x ULN2 (or higher)
Musculoskeletal
OsteonecrosisSymptomatic and interfering with function2 (or higher) (avascular necrosis)
OsteoporosisSymptomatic and requiring treatment3 (or higher)
Neurology/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 that 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 treatment3 (or higher)
Pneumonitis/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 (e.g. cough, dyspnoea, fever, 
Renal
HaematuriaMacroscopic (or dipstick +++) confirmed on 2 separate occasions2 (or higher)
Renal impairmentCreatinine > 1.5 ULN or creatinine clearance < 30mL/min2 (or higher)
Other
Allergic reactionUrticaria, drug fever > 38°C and/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

Phototherapy toxicity

Required minimum dose of 3 treatments per week

Adverse eventBrief description of minimum grade of toxicityNational Institutes of Health
common toxicity criteria grade
Severe photosensitivity reactionErythema with desquamation3 (or higher)
PruritisIntense or widespread and interfering with activities of daily living (ADLs)3 (or higher)
Development of melanoma  
Development of non melanoma skin cancer  
Development of more than 10 actinic keratoses  
Nausea (PUVA)Oral intake significantly decreased. A minimum of 3 doses should be trialled2 (or higher)
More than 200 combined phototherapy treatments  

Apremilast

Required minimum dose of 30 mg twice daily

Adverse eventBrief description of minimum grade of toxicityNational Institutes of Health
common toxicity criteria grade
Gastrointestinal
DiarrhoeaIncrease of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline2 (or higher)
NauseaOral intake decreased without significant weight loss, dehydration or malnutrition2 (or higher)
Vomiting3-5 episodes (separated by 5 minutes) in 24 hrs2 (or higher)
Abdominal painModerate pain; limiting instrumental ADL2 (or higher)
GORDModerate symptoms; medical intervention indicated2 (or higher)
General Disorders/administrative site
FatigueFatigue not relieved by rest; limiting instrumental ADL2 (or higher)
Weight decrease10 - <20% from baseline; nutritional support indicated2 (or higher)
Immune System
HypersensitivityIntervention or interruption to treatment indicated; responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics); prophylactic medications indicated for <=24 hrs2 (or higher)
Infections/infestations
BronchitisModerate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, antiviral)2 (or higher)
Upper respiratory tract infectionModerate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, antiviral)2 (or higher)
Decreased appetiteOral intake altered without significant weight loss or malnutrition; oral nutritional supplements indicated2 (or higher)
Musculoskeletal/connective tissue
Back painModerate back pain; prescription analgesics indicated; limiting instrumental ADL2 (or higher)
Nervous system
MigraineModerate pain; limiting instrumental ADL2 (or higher)
Tension headacheModerate pain; limiting instrumental ADL2 (or higher)
Psychiatric
InsomniaModerate difficulty falling asleep, staying asleep or waking up early2 (or higher)
Respiratory/thoracic/mediastinal
CoughModerate symptoms, medical intervention indicated; limiting instrumental ADL2 (or higher)
Skin/subcutaneous tissue
RashLocalized; local intervention indicated (e.g., topical antibiotic, antifungal, or antiviral)2 (or higher)

Deucravacitinib

6 mg once daily

 

Adverse event

 

Brief description of minimum grade of toxicity

National Institutes of Health
common toxicity criteria grade
Infections
Upper respiratory tract infectionsModerate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, antiviral)2 (or higher)
Herpes simplex infectionsModerate symptoms; oral intervention indicated (e.g. antiviral)2 (or higher)
Cardiovascular
HypertensionRecurrent/persistent rise of > 20 mmHg diastolic BP or rise to > 150/90 on 2 occasions if BP previously normal2 (or higher)
Dermatology/skin

Acneiform rash/folliculitis

 

Papules and/or pustules covering 10-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness2 (or higher)
Gastrointestinal
DiarrhoeaIncrease of 4-6 stools/day over pre-treatment2 (or higher)
NauseaPersistent nausea resulting in decreased oral intake2 (or higher)
Oral ulcersPseudomembranes or ulcerations2 (or higher)
Laboratory abnormalities
Creatine phosphokinase and rhabdomyolysis2.5 x ULN - 5 x ULN2 (or higher)
TransaminasesALT and/or AST > 2.5 x ULN or ALT and/or AST > 1.5 x ULN on 3 occasions over a 3-month period2 (or higher)
Triglycerides50 mg/dL - 300 mg/dL; 1.71 mmol/L - 3.42 mmol/L1 (or higher)
Musculoskeletal
Back pain   Moderate back pain; prescription analgesics indicated; limiting instrumental ADL2 (or higher)
ArthralgiaJoint pain causing greater than minimal interference with usual social and functional activities2 (or higher)
Other
HeadacheSevere pain: pain or analgesics that severely interfere with activities of daily living3 (or higher)
Page last updated: 1 April 2024.
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