Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Pegloticase, a methoxyPEG-conjugated mammalian recombinant uricase, has been approved in the US and EU for the treatment of chronic gout refractory to xanthine oxidase inhibitors. The pegloticase development program included 2 replicate randomized placebo-controlled trials (RCTs) followed by an open-label extension (OLE) study for a maximum therapy duration of up to 3 years.1,2 The pegloticase trials were unique in enrolling a majority of patients with baseline tophi (155/212 or 73%) and in the use of detailed digital quantitative assessment of each tophus. Here we present data on long-term treatment with pegloticase and tophus response rates as a function of tophus size.
Methods: Patients enrolled in the RCTs (n=212) were ≥18 years of age with baseline serum uric acid (UA) ≥8 mg/dL and at least 1 of the following: ≥3 self-reported gout flares in the past 18 months, ≥1 tophi, or gouty arthropathy; and contraindication to allopurinol or failure to normalize UA after ≥3 months of treatment at the maximum medically appropriate dose. Target subcutaneous tophi identified at baseline were photographed and assessed at multiple study time points using computer-assisted quantitative digital image analysis in patients receiving pegloticase (8 mg; q2wks or q4wks) or placebo in the RCTs, and pegloticase in the OLE. Complete response was defined as complete resolution of the target tophus. Tophus size was assessed at the baseline visit of the RCTs and categorized as small (<250 mm2), medium (250-750 mm2), or large (>750 mm2).
Results: This tophus size analysis focused on patients receiving the approved twice-monthly pegloticase dose who entered the OLE study. These included patients treated with either q2wk pegloticase (both UA responders and nonresponders; see table for definition) or placebo in the RCTs who received q2wk pegloticase at OLE study entry. The table presents the number of tophi undergoing complete resolution for each of these subgroups by tophus size. Among patients who showed response to therapy, the majority of small and medium tophi resolved within 6-9 months of therapy. For larger tophi, 12 to 18 months of therapy resulted in complete response in over 60% of tophi.
Conclusion: Many small and medium subcutaneous tophi resolved within the first 6 months of pegloticase therapy. These data show that substantial incremental benefit in tophus response for unresolved small to medium tophi can be gained with 9-12 months of therapy in UA responders. Longer periods of treatment (up to 18 months) with pegloticase were shown to resolve large tophi.
References:
1. Sundy et al. JAMA. 2011.
2. Becker et al. Ann Rheum Dis. 2012.
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Percentage of Target Tophi With Complete Response Over Time Based on Size
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Pegloticase q2wks UA Responders* in the RCTs
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Study Visit |
Small <250 mm2 |
Medium 250-750 mm2 |
Large >750 mm2 |
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RCT 25 weeks Total n**=37 |
42% (11/26) |
30% (7/23) |
8% (1/12) |
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OLE 13 weeks Total n=35 |
76% (19/25) |
55% (12/22) |
8% (1/12) |
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OLE 25 weeks Total n=34 |
84% (21/25) |
67% (14/21) |
18% (2/11) |
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OLE 53 weeks Total n=32 |
86% (19/22) |
65% (13/20) |
18% (2/11) |
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OLE 77 weeks Total n=32 |
79% (19/24) |
90% (18/20) |
64% (7/11) |
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Progressing tophi at 53 weeks Total n=32 |
0/22 |
0/20 |
0/11 |
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Pegloticase q2wks UA Nonresponders* in the RCTs
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RCT 25 weeks Total n=30 |
6% (1/17) |
16% (3/19) |
6% (1/18) |
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OLE 13 weeks Total n=30 |
27% (4/15) |
32% (6/19) |
0/15 |
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OLE 25 weeks Total n=18 |
67% (4/6) |
36% (5/14) |
0/11 |
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OLE 53 weeks Total n=21 |
60% (6/10) |
38% (6/16) |
8% (1/13) |
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OLE 77 weeks Total n=19 |
60% (6/10) |
27% (4/15) |
8% (1/12) |
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Progressing tophi at 53 weeks Total n=21 |
0/10 |
6% (1/16) |
23% (3/13) |
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Placebo → q2wks at OLE Entry
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RCT 25 weeks Total n=37 |
6% (1/17) |
7% (2/31) |
0/20 |
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OLE 13 weeks Total n=30 |
44% (7/16) |
26% (6/23) |
0/16 |
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OLE 25 weeks Total n=25 |
85% (11/13) |
50% (11/22) |
33% (4/12) |
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OLE 53 weeks Total n=21 |
100% (12/12) |
82% (14/17) |
90% (9/10) |
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OLE 77 weeks Total n=21 |
92% (11/12) |
94% (16/17) |
70% (7/10) |
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Progressing tophi at 53 weeks Total n=21 |
0/12 |
0/17 |
0/10 |
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*Responders were patients who met the primary endpoint of UA reduction defined as UA <6 mg/dL for 80% of time during RCT study months 3 and 6. **Total n is all patients in the subgroup irrespective of tophus response. |
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Disclosure:
R. T. Keenan,
Savient Pharmaceuticals, Inc.,
5;
N. Dalbeth,
Takeda, Ardea, AstraZeneca, Novartis, Abbott, Fonterra, and Roche,
9,
Fonterra,
2,
Novartis, Savient,
8;
H. S. B. Baraf,
Savient, Takeda, Regeneron, and Ardea,
2,
Savient, Takeda,
9,
Takeda, Savient,
8.
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