Background/Purpose:
Effectiveness of the IL-1 receptor antagonist anakinra, in resolving flares of acute gout, has been reported in several case series. Here, studying a VA gout cohort with a plurality of minorities, we analyzed patient characteristics in those who needed anakinra prescription to control acute gout flares. In doing so we tested the hypothesis that anakinra was prescribed for gout patients who were sicker (more comorbidities and ultimate mortality), and with higher urate burden (uncontrolled hyperuricemia, palpable tophi). We also analyzed ethnic/racial factors, since in East Asians the ABCG2 variant Q141K is very common (with an allele frequency up to 0.5) in gout. An emerging line of investigation links inflammation with the ABCG2 Q141K variant, and is associated with hyperuricemia and subsequent early onset tophaceous gout. ABCG2 Q141K inhibits autophagy and may increase systemic inflammation.

Methods:
More than 6000 patients fulfilling 2015 ACR/EULAR criteria for gout were seen at the VA between 01/2003 and 01/2015, with more than 1300 of these evaluated at least once for management by Rheumatology. During this time period, 14 patients (100% male) received anakinra at varying times, for a total of 55 courses. Demographics of the gout cohort were 52% White, 12% Black, 34% East Asian (including ~25% Pacific Islanders), and 2% other. In retrospective case-control analyses, for each patient, 4 age and gender matched controls were chosen. Each patient’s first visit with the Rheumatology department was analyzed for factors predictive of the patient eventually requiring anakinra for gout. Demographics, urate burden, baseline co-morbidities, and all-cause mortality were analyzed for anakinra use.

Results:
Patients who were prescribed or not prescribed anakinra had no significant difference in mean number of comorbidities, (mean of 3.9 in anakinra, 3.1 in controls), p = 0.08, CI -0.11 to 1.65. Patients receiving anakinra were more likely to have very poorly controlled hyperuricemia and a high body urate burden at baseline (anakinra group 10/14 with tophi vs. controls 17/56 with tophi, p = 0.018; anakinra group had mean serum urate of 10.2 mg/dL vs. 7.6 mg/dL in controls, p = 0.0002). The anakinra treated group had higher all-cause mortality (7/14 in anakinra group, 9/56 in controls p = 0.012) as well as greater predominance of East Asian patients (8/14 in anakinra group vs. 16/56 in control group, p = 0.049). In contrast, the distribution of Black patients was not statistically significant between groups (p = 0.18)

Conclusion:
Anakinra use for acute gout was associated with patient characteristics including East Asian descent, uncontrolled hyperuricemia and a high body urate burden (reflected by palpable tophi), and significant increases in both the number of co-morbidities and all-cause mortality. The results suggest not only that in gout, patients who are sicker and have less poorly controlled serum urate, more frequently require anakinra to help control acute gout flares. Moreover, the possibility that East Asian patients have a genetic predisposition for more refractory inflammation in gout merits further investigation.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-case-control-study-of-anakinra-use-for-acute-gout-in-a-va-patient-cohort-reveals-association-with-east-asian-descent-high-urate-burden-and-increased-co-morbidities-and-all-cause-mortality/