Background/Purpose: A Delphi exercise reached consensus on a definition for gout remission that included serum uric acid (sUA) <6 mg/dL, no flares, resolution of all tophi, limited pain, and low disease impact by patient global assessment (PGA).¹ The frequency with which these criteria are achieved in response to treatment has not been assessed. Our study evaluated these criteria using results from patients with chronic refractory gout who received pegloticase (8 mg every 2 weeks), a mammalian recombinant uricase conjugated to polyethylene glycol approved for treatment of adults with chronic gout refractory to oral urate lowering therapy².

Methods: The results from two identical randomized controlled trials (RCTs) of pegloticase were analyzed.² Patients received 6 months of treatment with 8 mg of pegloticase or placebo, and responders were defined as those with persistent urate lowering². Overall, 42% (n=36) of the patients who received pegloticase 8 mg every 2 weeks were responders in the RCTs and 34 continued in the open-label extension. Initially, individual patient data was reviewed to establish the frequency with which pegloticase responders met the proposed remission criteria.¹ Subsequently, using mixed modelling, we determined the best criteria for a “complete response” (CR) using a repeated-measures, mixed-effects model to relate the time when a patient’s response was noted, assessed by patient global assessment (PGA), SF-36 bodily pain scores, visual analog scale pain levels, numbers of tender and swollen joints, number of flares, and the degree of tophus resolution controlling for repeated measures. Variables were eliminated by dropping the least statistically significant item. All components of the final model were statistically significant.

Results: Of 34 pegloticase responders, 29 (85.3%) met the published criteria for remission. However, comparison of various components of the composite criteria indicated weak or absent correlations. Mixed effects modelling defined the following criteria for a CR: sUA <6 mg/dL, resolution of all measured tophi, PGA ≤1, swollen joint count ≤1, and tender joint count ≤1. The mean time from the beginning of the RCT to reach CR criteria was 11.5 months. All patients who achieved a CR maintained it until the end of follow-up. The mean duration of CR was 507.4 days and there was a significant inverse relationship between the time to CR and the duration of the response (P=0.0008).

Conclusion:

These results defined criteria for a CR in individuals with chronic refractory gout treated with pegloticase, suggesting that, the majority of patients who persistently lower sUA, reach criteria for CR, and do so within 1 year from the initiation of therapy. CR persisted for the length of treatment.

This composite CR index can serve as an evidence-based target goal for a “Treat to Target” strategy in clinical practice and in future clinical trials.

1. deLautour H, et al. Arthritis Care Res. 2016;68:667. 2. Sundy JS, et al. JAMA. 2011;306:711.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evidence-based-development-of-criteria-for-complete-response-in-patients-with-chronic-refractory-gout/