POS0239 ACHIEVEMENT OF “GOUT REMISSION” DURING INTENSIVE URATE-LOWERING OVER 52 WEEKS OF PEGLOTICASE THERAPY

Background:

The harmful effects of gout are apparent with growing evidence supporting detrimental musculoskeletal and systemic health consequences of this condition,[1-3] particularly of acute gout flares.[4-7] Akin to treatment goals of other rheumatic diseases, the concept of treating gout to remission is important for improving patient care and better understanding its impact on patient quality of life (QOL). Gout remission has been previously defined as meeting all of the following criteria: serum urate level (SU) <6 mg/dL, absence of acute gout flare, absence of tophi, minimal gout-related pain (<2 on a 10-point scale), and minimal gout-related quality of life (QOL) impact (patient global assessment of gout [GA]<2 on a 10-point scale) over a 12-month period.[8]

Objectives:

Here we investigate clinical trial data^[9,10] to evaluate gout remission rates with intensive urate-lowering.

Methods:

This post hoc analysis of MIRROR RCT data examined gout remission in patients administered 52 weeks of pegloticase therapy (8 mg infusion every 2 weeks). Using available MIRROR RCT data, gout remission was defined as meeting all of the following criteria: SU<6 mg/dL, no gout flare during the treatment month of interest, physician GA (PhGA) ≤1 (score range: 0-10 points), Health Assessment Questionnaire Pain (HAQ-Pain) ≤10 (0-100 points), swollen joint count (SJC) ≤1 (0-66 joints), and resolution of ≥1 tophus (in patients with tophi prior to treatment). Though methotrexate (MTX) co-therapy increases pegloticase SU-lowering response rate and‌‌ lowers infusion reaction risk,^[9] all evidence indicates that MTX itself does not directly impact examined gout remission criteria. Therefore, patients receiving MTX and placebo (PBO) as co-therapy to pegloticase were combined for this remission analysis. Patients with 2 consecutive SU >6 mg/dL after Week 2 discontinued treatment and were excluded from analysis after pegloticase discontinuation (only data from patients on-therapy at the listed timepoint included).

Results:

Of the 145 patients who received ≥1 pegloticase infusion (Table 1), 90 (70 MTX, 20 PBO) remained on treatment through Week 24 (SU<6 mg/dL in 89/90 [99%]) and 74 (58 MTX, 16 PBO) remained on treatment through Week 52 (SU<6 mg/dL in 73/74 [99%]). At Week 24, 20% (18/90) of patients had achieved gout remission; at Week 52, 47% (35/74) of patients had achieved gout remission (Figure 1). The proportion of patients meeting each remission criterion had gains between Week 24 and Week 52 of therapy, most notably tophus resolution (34% to 68%), PhGA (52% to 74%), HAQ-Pain (48% to 73%), and flare (no flare during treatment Month 6 [82%; Weeks 20-24] and 12 [97%; Weeks 48-52]). Resolution of ≥1 tophus was the criterion met by the fewest number of patients both at Week 24 (17/50 [34%]) and Week 52 (28/41 [68%]).

Conclusion:

Pegloticase treatment resulted in achievement of gout remission in nearly half (47%) of patients remaining on therapy for 52 weeks. These data demonstrate that successful intensive SU-lowering with pegloticase and subsequent urate depletion[^11,12] result in marked improvements in both gout signs/symptoms and patient QOL. Additionally, these data further demonstrate that many patients benefit from pegloticase treatment that is longer than 6 months.

REFERENCES:

[1] Francis-Sedlak M, et al. Rheumatol Ther 2021;8:183-97. [2] Khanna P, et al. J Clin Med 2020;9:3204. [3] Amatucci AJ, et al. Rheumatol Ther 2023;10:809-23. [4] Pillinger M, et al. Arthritis Rheumatol. 2022;74 (suppl 9). [5] Cipolletta E, et al. JAMA 2022;328:440-50. [6[Cipolletta E, et al. Arthritis Rheumatol 2023;75:1638-47. [7] Schlesinger N, et al. Ann Rheum Dis 2022;74 (suppl 9). [8] de Lautour H, et al. Arthritis Care Res (Hoboken) 2016;68:667-72. [9] Botson JK, et al. Arthritis Rheumatol 2023;75:293-304. [10] Botson JK, et al. ACR Open Rheumatol 2023;5:407-18. [11] Dalbeth N, et al. Rheumatology (Oxford) 2022;61:4898-904. [12] Dalbeth N, et al. Arthritis Rheumatol 2023;74 (suppl 9).

Acknowledgements:

NIL.

Disclosure of Interests:

Yael Klionsky MediQ, Amgen, Inc., AstraZeneca, and Lilly, Karina Torralba Aurinia, AstraZeneca, Bioclinica, Amgen, Inc., AstraZeneca, Human Genome Sciences, Novartis, and UCB, Katie Obermeyer Amgen, Inc., Amgen, Inc., Lissa Padnick-Silver Amgen, Inc., Amgen, Inc., Brian LaMoreaux Amgen, Inc., Amgen, Inc., Gordon Lam Amgen, Inc., Amgen, Inc.