Abstract
BackgroundGout is a heterogeneous inflammatory disease with numerous clinical manifestations. A composite means to assess the impact of therapy on numerous aspects of gout could be useful.MethodsResults from patients treated with pegloticase or placebo in two randomized clinical trials and their open-label extension were assessed using a novel evidence-based Gout Multivariable Improvement Measure (GMIM) derived from previously reported criteria for remission and complete response. Improvement was defined as serum urate (sU) < 6 mg/dL and absence of flares during the preceding 3 months plus 20, 50, and 70% improvement in tophus size, patient global assessment, pain, and swollen and tender joints.ResultsPatients treated with pegloticase manifested a significantly greater GMIM20, 50, and 70 response vs those treated with placebo (GMIM20 at 6 months 37.1% vs 0%, respectively). Higher response rates were significantly more frequent in subjects with persistent urate lowering (GMIM 58.1% at 6 months) in response to pegloticase versus those with only transient urate lowering (GMIM 7.1% at 6 months). However, when the requirement for a decrease in sU to < 6 mg/dL was omitted, a substantial percentage of subjects with transient urate lowering met the GMIM clinical criteria. A sensitivity analysis indicated that gout flares contributed minimally to the model. The response measured by GMIM persisted into the open-level extension for as long as 2 years. Finally, subjects who received placebo in the randomized control trials, but pegloticase in the open-label extension, manifested GMIM responses comparable to that noted with pegloticase-treated subjects in the randomized controlled trials.ConclusionsGMIM captures changes in disease activity in response to treatment with pegloticase and may serve as an evidence-based tool for assessment of responses to other urate-lowering therapies in gout patients.
Highlights
Gout is a heterogeneous inflammatory disease with numerous clinical manifestations
Patients from the Randomized controlled trial (RCT) could continue into the open-label extension (OLE) in which they were given the choice of receiving pegloticase q2w or q4w [35]
Some criteria contributed little to the complete response model, such as pain and flares [34], they were included in the final Gout Multivariable Improvement Measure (GMIM) because they were thought to be important in evaluating patients with gout
Summary
Gout is a heterogeneous inflammatory disease with numerous clinical manifestations. A composite means to assess the impact of therapy on numerous aspects of gout could be useful. Inflammatory rheumatic diseases are generally multifaceted disorders, and the complex pathology underlying these conditions makes it difficult to assess patient status and the efficacy of therapy with a single representative outcome measure [1]. Even though the cause of gout, namely hyperuricemia, is known, patients experience a wide range of symptoms, including severe pain, acute and persistent inflammatory arthritis, tophi, and disability associated with both flares and chronic disease [15, 16]. Assessment of urate-lowering therapy (ULT) for this disease has focused primarily on the ability to lower serum urate (sU) and decrease in the frequency of flares [21,22,23,24,25], some trials have included additional endpoints to address effects of treatment on pain, arthritis, and disability [26, 27]
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