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. 2024 Apr 12;26(1):86.
doi: 10.1186/s13075-024-03318-5.

Urate-lowering therapy, serum urate, inflammatory biomarkers, and renal function in patients with gout following pegloticase discontinuation

Emily E Holladay  1 , Amy S Mudano  2 , Fenglong Xie  1 , Jingyi Zhang  1 , Ted R Mikuls  3 , Brian LaMoreaux  4 , Lissa Padnick-Silver  4 , Jeffrey R Curtis  5   6
Affiliations

Urate-lowering therapy, serum urate, inflammatory biomarkers, and renal function in patients with gout following pegloticase discontinuation

Emily E Holladay et al. Arthritis Res Ther. .

Abstract

Background/purpose: Little is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU), inflammatory biomarkers, and renal function following pegloticase discontinuation.

Methods: We conducted a retrospective analysis of gout patients who discontinued pegloticase using the Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 to 6/2022. We defined discontinuation as a gap ≥ 12 weeks after last infusion. We examined outcomes beginning two weeks after last dose and identified ULT therapy following pegloticase discontinuation. We evaluated changes in lab values (SU, eGFR, CRP and ESR), comparing on- treatment (≤ 15 days of the second pegloticase dose) to post-treatment.

Results: Of the 375 gout patients discontinuing pegloticase, median (IQR) laboratory changes following discontinuation were: SU: +2.4 mg/dL (0.0,6.3); eGFR: -1.9 mL/min (- 8.7,3.7); CRP: -0.8 mg/L (-12.8,0.0); and ESR: -4.0 mm/hr (-13.0,0.0). Therapy post-discontinuation included oral ULTs (86.0%), restarting pegloticase (4.5%), and no documentation of ULT (9.5%), excluding patients with multiple same-day prescriptions (n = 17). Oral ULTs following pegloticase were: 62.7% allopurinol, 34.1% febuxostat. The median (IQR) time to starting/restarting ULT was 92.0 days (55.0,173.0). Following ULT prescribing (≥ 30 days), only 51.0% of patients had SU < 6 mg/dL. Patients restarting pegloticase achieved a median SU of 0.9 mg/dL (IQR:0.2,9.7) and 58.3% had an SU < 6 mg/dL.

Conclusion: Pegloticase treats uncontrolled gout in patients with failed response to xanthine oxidase inhibitors, but among patients who discontinue, optimal treatment is unclear. Based on this analysis, only half of those starting another ULT achieved target SU. Close follow-up is needed to optimize outcomes after pegloticase discontinuation.

Keywords: Discontinuation; Gout; Pegloticase; Restart; Treatment gap.

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Conflict of interest statement

EEH, ASM, FX, and JZ declare no conflicts of interest. TRM receives support from Elsevier, UpToDate, Horizon (now Amgen Inc.), Pfizer, Sanofi, UCB, and the Rheumatology Research Foundation. BL and LPS are employees of and stockholders in Horizon Therapeutics (now Amgen Inc.). JRC receives support for unrelated work from AbbVie, Amgen, Aqtual, Bendcare, BMS, CorEvitas, FASTER, GSK, Janssen, Lilly, Moderna, Novartis, Pfizer, Sanofi, Scipher, Setpoint, TNacity Blue Ocean, and UCB.

Figures

Fig. 1
Fig. 1
Attrition Table for the ACR-RISE Registry Pegloticase Discontinuation Cohort. ICD = international classification of disease code; SU = serum urate; eGFR = estimated glomerular filtration rate; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein
Fig. 2
Fig. 2
ULT Initiated After Pegloticase Discontinuation (n = 358a). ULT = urate-lowering therapy. a Patients prescribed multiple ULT’s for medicine 1 or 2, after pegloticase discontinuation, were censored
Fig. 3
Fig. 3
Probability of Starting a ULT Following Pegloticase Discontinuation. Pegloticase discontinuation is defined as 14 days following the last pegloticase infusion. The gray shaded region represents the 95% confidence interval. ULT = urate-lowering therapy
Fig. 4
Fig. 4
Changes in Laboratory Values Following Pegloticase Discontinuation. SU = serum urate
See this image and copyright information in PMC

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