HARM APPRAISAL

Is the objective of the article on harm similar to your clinical dilemma?

• Yes the objective of the article on harm is similar to our clinical dilemma.

• Our case is a 50 year old male patient with gout, evaluated for azotemia.

• Dilemma - if the patient’s uric acid levels are markedly elevated is it safe to administer high does of allopurinol even when the creatinine clearance level of the patient is low?

• Objective of the study: “To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate.”

Were there clearly identified comparison groups?

• Yes. The study included patients with gout receiving regular treatment with allopurinol for at least 1 month before their inclusion in the analysis were reviewed.

• Retrospective cohort study divided the patients into two groups.

• Group A comprised patients whose allopurinol maintenance dose matched the dose schedule recommended by Hande et al according to their creatinine clearance rate

• Group B comprised patients whose maintenance dose exceeded the dose recommended for their creatinine clearance rate.

Were the exposures and outcomes measured in the same way in the groups compared?

• The study was not blinded, so we can not deduct if surveillance bias had occurred.

Was follow-up sufficiently long and complete?

• Yes the follow up was sufficiently long and complete.

• The follow up last for a mean duration 3.3 years, with allopurinol dosing ranging from 100 to 450 mg.

• This would be ample time to note any adverse effects of allopurinol in each study group.

Is the temporal relationship between the exposure and outcome correct

and dose response gradient present?

• No. The study’s intention was not to measure a temporal response between the exposure and outcome, but to measure if using a high dose regimen would increase the prevalance of established adverse effects from Allopurinol treatment.

What is the magnitude of the association between exposure and outcome? Was the estimate of the risk precise?

Are the study patients similar to my own?

YES

Our patient• Male• 50 years old• Azotemia• Gout

Study characteristics• 118 out of 120 patients

were male• Mean age of 52 years old• Studied the effects of

allopurinol on patients with gout in relations to creatine clearance.

Should I stop the Exposure?

• How large and precise is the risk of harm?• What are the consequences if I withdraw the

exposure?• Do I have any alternative for the exposure?

• How large and precise is the risk of harm?– The risk of harm from high dose allopurinol is low.

However increasing allopurinol dosing should be done with caution.

• What are the consequences if I withdraw the exposure?– The usual complications of gout would occur, such

as:• Gout spreading to other joints• Inflamed tophi• Damage to the kidneys

• Do I have any alternative for the exposure?– Febuxostat– Pegloticase (Urate oxidase) – Probenecid (Uricosuric)– Ethylenediaminetetraacetic acid (EDTA)