CONFIRMS was a Phase 3, double-blind randomized controlled trial (RCT) that examined the comparative efficacy and safety of febuxostat in 2,269 subjects, who were randomized in 1:1:1 ratio to a daily dose of febuxostat 40 mg, febuxostat 80 mg, or allopurinol 300 mg (200 mg in patients with moderate renal impairment) [
13]. In a recent article published in
BMC Musculoskeletal Disorders, Wells et al., conducted a secondary analysis of the CONFIRMS trial, analyzing the efficacy and safety outcomes for African-Americans (10%) versus Caucasians (82%) enrolled in the trial [
19]. They reported that febuxostat at both doses as well as allopurinol at the 300/200 mg dose was equally efficacious in achieving target serum urate < 6 mg/dl in both African-Americans as compared to Caucasians, as well as in subgroups of patients with mild renal insufficiency or moderate renal insufficiency. The risk of gout flares and the safety profile also seemed comparable between African-Americans and Caucasians, i.e., similar proportions reported at least one adverse event. Febuxostat 80 mg dose was more efficacious than 40 mg dose and allopurinol 300/200 mg dose. However, the low dose of allopurinol used in this study is effective in achieving target serum urate < 50% gout patients [
20], and is considered suboptimal as per the current state-of-the-art gout treatment, where titration to the maximum approved dose of 800 mg in the U.S. is recommended, since the rate of allopurinol hypersensitivity seems to be independent of allopurinol dose used [
21], contrary to what was previously suspected. An interesting observation, not discussed by authors, was that a lower proportion of African-Americans had liver function test abnormality (ALT elevation 2-times or higher, 2% vs. 13%, respectively) compared to Caucasians; however, these data were provided as an aggregate and not by treatment group and the rate of AST elevations seemed similar. Another observation was that febuxostat 40 mg was associated with significantly lower rates of achieving target serum urate < 6 mg/dl in African-Americans than Caucasians (38% vs. 55%, p = 0.046). The authors attribute this, at least partially, to lower compliance with Febuxostat 40 mg in African-Americans compared to Caucasians (66% vs. 82%), greater for this treatment arm than the other two (febuxostat 80 mg and allopurinol).
This is the first large randomized gout trial, for which separate analyses have been performed by race. It is reassuring to see that the chances of successful treatment with ULT are not different between African-Americans and Caucasians. These findings have significant implications. They support the notion that if treated optimally, both African-Americans and Caucasians with gout respond similarly to ULT. More importantly, the safety seemed similar in African-Americans and Caucasians with gout, and a possibility of lower risk of liver toxicity in African-Americans, which should be investigated further in future studies. The results of this study provide at least one way to reduce racial disparities in heath care of patients with gout, i.e., by increasing awareness of the public and providers' that patients' race/ethnicity does not impact the efficacy and safety of ULT in gout. Evidence-based gout quality indicators published 7 years ago emphasize the importance of achieving target serum urate < 6 mg/dl and using ULT as the main treatment strategy in gout [
22].
What is known about racial disparities and their elimination in other musculoskeletal disorders? Racial [
23,
24] disparities in joint arthroplasty have been demonstrated with African Americans and Hispanics with lower utilization rates of knee and hip arthroplasty. A recent study also indicates smaller gains in well-being and pain/functional improvements after total joint arthroplasty in African Americans compared to Caucasians [
25]. Fewer black patients (16%) with rheumatoid arthritis preferred aggressive treatment compared with white patients (51%) [
26]. To our knowledge, very limited literature exists regarding how to best eliminate these disparities. It seems likely that increasing patient awareness of gout and its effective treatments and institution of aggressive treatment of gout in African Americans are two strategies that are likely to be most helpful first steps in addressing health disparities in gout.