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. 2020 Jun 29;22(1):164.
doi: 10.1186/s13075-020-02254-4.

Development of a multivariable improvement measure for gout

Naomi Schlesinger  1 , N Lawrence Edwards  2 , Anthony E Yeo  3 , Peter E Lipsky  4
Affiliations

Development of a multivariable improvement measure for gout

Naomi Schlesinger et al. Arthritis Res Ther. .

Abstract

Background: 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.

Methods: Results 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.

Results: Patients 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.

Conclusions: GMIM 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.

Keywords: Disease activity; Gout; Pegloticase.

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Conflict of interest statement

NS reports research grants from Pfizer and Amgen and advisory board/consulting fees from Novartis, Horizon Therapeutics, Selecta Biosciences, Olatec, IFM Therapeutics, and Mallinckrodt Pharmaceuticals.

NLE reports consulting fees from Astra Zeneca, Horizon Therapeutics, Ironwood Pharmaceuticals, and SOBI International.

AEY reports consulting from Horizon Therapeutics.

PEL reports consulting fees from Horizon Therapeutics.

Figures

Fig. 1
Fig. 1
Percentage of subjects treated with pegloticase q2w or placebo reaching GMIM criteria at 3 and 6 months in the RCTs. Number of evaluable subjects is shown for each group. The percentage of responders is shown above the bars. a Results for all GMIM criteria and b Results for all criteria except urate < 6.0 mg/dL. The statistical analysis of the data is shown in the supplementary material
Fig. 2
Fig. 2
Percentage of responders and nonresponders to pegloticase or placebo-treated subjects meeting GMIM criteria at 3 and 6 months. Data show percentage of subjects meeting GMIM criteria including serum urate < 6 mg/dL. Number of evaluable subjects is shown for each group. The percentage of responders is shown above the bars. The statistical analysis of the data is shown in the supplementary material
Fig. 3
Fig. 3
Percentage of responders and nonresponders to pegloticase or placebo-treated subjects meeting GMIM criteria at 3 and 6 months. Data show percentage of subjects meeting GMIM criteria excluding serum urate < 6 mg/dL. Number of evaluable subjects is shown for each group. The percentage of responders is shown above the bars. The statistical analysis of the data is shown in the supplementary material
Fig. 4
Fig. 4
Sensitivity analysis of the GMIM model. Data show the percentage of responders and nonresponders to pegloticase or placebo-treated subjects meeting GMIM criteria at 3 and 6 months. Data show percentage of subjects meeting the GMIM criteria excluding serum urate < 6 mg/dL. In each figure, data are calculated omitting one criterion. Number of evaluable subjects is shown for each group. The percentage of responders is shown above the bars. Data are shown in supplementary table 4
Fig. 5
Fig. 5
Percentage of subjects with GMIM20, 50, and 70 responses during the OLE for patients treated with biweekly pegloticase in the RCT and OLE. a Results for all criteria including urate < 6.0 mg/dL and b Results for all GMIM criteria excluding urate < 6 mg/dL
Fig. 6
Fig. 6
Percentage of subjects with GMIM20, 50, and 70 responses during the OLE for patients who were treated with placebo in the RCT and biweekly pegloticase in the OLE. a Results for all GMIM criteria including urate < 6 mg/dL and b Results for all criteria excluding urate < 6.0 mg/dL
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