Background Allopurinol is the most commonly used first-line urate-lowering therapy for the management of gout. Although allopurinol is generally safe, it is associated with severe allopurinol-hypersensitivity syndrome (AHS) (i.e., Steven Johnson Syndrome and Toxic Epidermal Necrolysis). AHS is fatal in up to 30% of cases. Patients with the human leukocyte antigen HLA-B*5801 are at higher risk of developing AHS. The prevalence of HLA-B*5801 and risk of AHS varies by race and is highest in Asians. The 2012 ACR gout guideline recommends testing for HLA-B*5801 in Asians prior to the allopurinol initiation, but the guideline did not take into account its cost-effectiveness.
Objectives We evaluate the cost-effectiveness of testing for HLA-B*5801 prior to initiation of allopurinol according to race.
Methods We modified a previously developed Markov decision model to evaluate the cost-effectiveness of testing for HLA-B*5801 prior to the initiation of allopurinol (300mg) – febuxostat (80mg) sequential therapy compared to treating with allopurinol (300mg) –febuxostat (80mg) sequential therapy without testing. Hypothetical patients in the testing strategy received a polymerase chain reaction test for HLA-B*5801 prior to the initiation of therapy. Patients that tested positive for HLA-B*5801 were assumed to be treated with febuxostat. Patients that tested negative for HLA-B*5801 and those in the no testing strategy were assumed to initially receive allopurinol. We took account of the variation in risk of hypersensitivity by race (Caucasians 0.0003; African Americans 0.0015; Asian Americans 0.0034) and prevalence of HLA-B*5801 by race (Caucasians 0.007; African Americans 0.038; Asian Americans 0.074). Patients on allopurinol could experience a minor (e.g., erythema multiforme minor) or major (e.g., Stevens-Johnson Syndrome) AHS event. Cost and quality-adjusted life years (QALYs) were evaluated over the lifetime of a hypothetical gout cohort. Finally, we conducted a sensitivity analysis to evaluate the effect variation in cost of testing, the prevalence of HLA-B*5801, and background AHS risk on the cost-effectiveness of testing.
Results Given a willingness-to-pay threshold of $110,000 per QALY, HLA-B*5801 testing is not cost-effective for Caucasians (incremental cost-effectiveness ratio $268,020), but it is cost-effective for African Americans (incremental cost-effectiveness ratio $91,870) and Asian Americans (incremental cost-effectiveness ratio $64,140). As the prevalence of HLA-B*5801 increases the incremental cost-effectiveness ratio of testing decreases (Figure 1). When the prevalence of HLA-B*5801 is greater than 0.029 testing is cost-effective.
Conclusions Testing for the presence of HLA-B*5801 is cost effective in African American and Asian Americans compared with accepted willingness-to-pay thresholds.
Disclosure of Interest E. Jutkowitz: None declared, M. Dubreuil: None declared, N. Lu: None declared, K. Kuntz: None declared, H. Choi Grant/research support from: Takeda and Astra-Zeneca, Consultant for: Takeda and Astra-Zeneca