INFLUENCE OF RENAL FUNCTION ON THE VELOCITY OF TOPHUS RESOLUTION AND ACHEIVEMENT OF DISEASE REMISSION IN PATIENTS WITH CHRONIC REFRACTORY GOUT TREATED WITH PEGLOTICASE

Background/Purpose: Impaired kidney function is a recognized comorbidity of gout,¹ but it is not known whether chronic kidney disease (CKD) alters the velocity of resolution of tophi or time required to achieve disease remission in response to pegloticase therapy in subjects with chronic refractory gout.

Methods: This analysis used results from two 6-month randomized controlled trials of pegloticase² in patients with chronic refractory gout to address these issues. Velocity of tophus resolution was determined in 18 subjects with chronic refractory gout and visible tophi who responded to pegloticase (8 mg every 2 weeks) with sustained serum urate reductions (<6 mg/dL) over 6 months. Achievement of remission³ was evaluated in all 34 such subjects who had persistent lowering of serum urate in response to biweekly pegloticase. eGFR was determined at baseline and after 3 and 6 months of treatment. Tophi were photographed and measured at baseline, 3, 4.5, and 6 months.

Results: At baseline, the mean area of photographed tophi was 585.8 mm². The velocity of tophus resolution for all subjects was 60.1 mm² per month. There was no significant relationship between baseline eGFR and velocity of tophus resolution (P=0.5) (Figure 1A). In addition, there were no significant differences in the velocity of tophus resolution for patients with Stage 1 chronic kidney disease (CKD) vs Stage 2 CKD (P=0.7), Stage 3 CKD (P=0.9), or Stage 4 CKD (P=0.7). The relationship between baseline CKD severity and time to achieve remission is shown in Figure 1B. Here, 29/34 (85.3%) subjects with persistent urate lowering in response to pegloticase achieved remission. There were no significant differences in the achievement of remission in those with various stages of CKD determined by eGFR. Notably, there was no significant change in eGFR in response to pegloticase therapy through the 6-month duration of the study.

Conclusion: The results from this analysis indicate that renal impairment does not compromise the ability of pegloticase to resolve tophi rapidly in patients who respond with sustained reductions in serum urate. They also suggest that severity of renal disease does not influence achievement of remission in pegloticase-treated subjects with chronic refractory gout who have persistent urate lowering.

References:

1.     Nyberg F, et al. Adv Ther. 2016;33:1180.

2.     Sundy JS, et al. JAMA. 2011;306:711.

3.     de Lautour H, et al. Arthritis Care Res (Hoboken). 2016;68:667.

Figure 1. Relationship between baseline eGFR and velocity of tophus reduction (A) and

times to remission in the subjects in the different CKD groups (B)