Results from a post hoc analysis published in ACR Open Rheumatology validated the proposed remission criteria for gout and defined new criteria for complete response in patients with chronic gout treated with pegloticase.
The Gout Activity Score, typically used to assess the activity of gout, does not provide a target for remission of gout. Other proposed gout remission criteria require specific goals to be met, and have not been tested in longitudinal clinical trials. Therefore, the objective of this study was to generate evidence-based criteria for gout remission and develop new criteria for complete response using data from pegloticase trials.
In this study, researchers performed a post hoc analysis on results from 2 identical randomized controlled trials (ClinicalTrials.gov Identifiers: NCT00325195 and NCT01356498) in which pegloticase and their open-label extension were evaluated for response to treatment. All patients in both trials were aged ≥18 years, had chronic refractory gout (baseline serum urate acid, ≥8.0 mg/dL) and met at least 1 of the following inclusion criteria: ≥3 self-reported gout flares in the past 18 months, ≥1 tophi, presence of gouty arthropathy, and contraindication to treatment with allopurinol or history of failure to normalize serum urate despite ≥3 months of treatment with the maximum medically appropriate allopurinol dose. All patients received flare-prevention medication and were randomly assigned to receive 6 months of treatment of either pegloticase 8 mg at each infusion, pegloticase 8 mg alternating with placebo, or only placebo.
The primary end point was classification as a responder to treatment, defined as a serum urate level less than 6.0 mg/dL for ≥80% of the time during the third and sixth months of the study. Secondary end points included resolution of tophi, reduction in the percentage of patients with gout flares and in the number of per-patient flares between months 1 to 3 and 4 to 6, reductions in tender joint counts and swollen joint counts, and patient-reported changes in pain, physical function, and quality of life. Mixed‐effects modeling was used to identify components that best correlated with time to maximum benefit.
Study results revealed that among the 56 patients treated with biweekly pegloticase, 27 (48.2%) met the remission criteria. Of the 32 responders to pegloticase who entered the open-label extension trial, 27 (84.4%) met the remission criteria. When the requirement for the lowering of serum urate level was waived, only 2 of 24 (8.3%) nonresponders and none of 43 patients who received a placebo met the clinical remission criteria.
Results from mixed modeling indicated that the final criteria for complete response were serum urate level <6 mg/dL, resolution of tophi, and a score of <2 for swollen joints, tender joints, and patient global assessment. Using these criteria, 23 of the responders (71.9%) met complete response criteria, and among patients who achieved complete response, mean duration for maintenance was 507.4 days.
This study had several limitations. First, data were derived from 2 identical trials and required confirmation with other data sets. Second, the results of the validation exercised for the complete response criteria were obtained from a cohort from the same trials used to generate the composite measure, and could be optimistically biased. Lastly, the analysis was conducted in patients with advanced gout who met the criteria for chronic refractory gout, and it remains to be determined whether the proposed criteria can be used for patients with less advanced gout.
Study researchers concluded that their results validated proposed gout remission criteria, and that the newly defined criteria for complete response in chronic gout treated with pegloticase may be used to influence the design and end points of future clinical trials.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Schlesinger N, Edwards NL, Khanna PP, Yeo AE, Lipsky PE. Evaluation of proposed criteria for remission and evidence‐based development of criteria for complete response in patients with chronic refractory gout. ACR Open Rheumatol. 2019;1(4):236-243.