Session Information
Date: Sunday, November 13, 2016
Title: Metabolic and Crystal Arthropathies - Poster I: Clinical Practice
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Pegloticase is a recombinant uricase conjugated to polyethylene glycol approved for the treatment of chronic refractory gout refractory. The pivotal clinical trials for pegloticase defined responders as patients with plasma uric acid (UA) <6.0 mg/dL for ³80% of the time during extensive monitoring from both the week 9 infusion to just before the week 13 infusion and from the week 21 infusion to week 25 (final visit). Nonresponders did not meet this stringent criterion, but had a substantial decrease in UA after the first pegloticase dose followed by a return to a UA level >6mg/dL after ~6 weeks of therapy.1Whether these subjects received persistent clinical benefit from the transient reduction in UA is not known and is the subject of this analysis.
Methods: This analysis used results from two randomized controlled trials (RCTs)1 to assess the clinical efficacy in responders and nonresponders to treatment (8 mg of pegloticase delivered every 2 weeks [q2w]). Serum UA was measured before each infusion and assessment of gout flares, tophus reduction, Patient Global Assessment (PGA), tender and swollen joints (TJC and SJC), pain measured with a 100 mm visual analog scale (VAS) and a variety of Patient Reported Outcomes were determined for four groups: responders, all nonresponders including those who exited the study and were not available for the UA assessments at 3 and 6 months, per-protocol (PP) nonresponders who received all planned pegloticase infusions in the 6-month RCTs, and patients who received placebo.
Results: The analysis included 36 responders, 49 nonresponders, 24 PP nonresponders, and 43 patients who received placebo. Responders exhibited mean reductions in serum UA to <0.5 mg/dL at 3 and 6 months. Both nonresponders and PP nonresponders had a transient decrease in UA that returned to a mean >6mg/dL by 7 weeks. Results for both responders and nonresponders indicated significant reduction in tophi and improvements from baseline in PGA, TJC, SJC, pain, and ASHI (Table). Improvements were greatest for responders, but were also significant for both groups of nonresponders. No significant improvements were observed in the patients who received placebo.
Conclusion: These results indicate that chronic refractory gout patients not achieving a protocol-defined biochemical response still have significant clinical benefits with pegloticase treatment. This suggests that the substantial, but transient, reduction in UA achieved in patients categorized as nonresponders in the RCTs can result in sustained clinical benefit. These benefits are not merely a result of being enrolled in a clinical trial or receiving hydrocortisone as prophylaxis for infusion reactions (IR) since they were not observed in patients who received placebo and a similar IR prevention protocol.
|
Tophus Resolution at 6 months |
Complete |
Partial |
||||||
| Responder (n=36) |
52.0% |
16% |
||||||
| Nonresponder (n=49) |
25.0 % |
25% |
||||||
| Per Protocol (PP) Nonresponder (35) |
26.9% |
26.9% |
||||||
| Placebo (n=43) |
10.0% |
20% |
||||||
| Time |
Mean |
SD |
P-value* |
Time |
Mean |
SD |
P-value* |
|
|
Flares |
Patient Global Assessment (PGA) |
|||||||
| Responder (n=36) | Responder (n=36) | |||||||
| Baseline |
2.1 |
1.9 |
– |
Baseline |
49.9 (n=35) |
28.1 |
– |
|
| 6 months |
1.0 |
1.4 |
P=0.009 |
6 months |
12.3 (n=36) |
14.2 |
p<0.0001 |
|
| Nonresponder (n=49) | Nonresponder (n=49) | |||||||
| Baseline |
1.3 |
1.5 |
– |
Baseline |
46.0 (n=49) |
28.5 |
– |
|
| 6 months |
0.6 |
1.0 |
P=0.0002 |
6 months |
22.7 (n=25) |
24.2 |
P=0.0009 |
|
| PP Nonresponder (n=24) | PP Nonresponder (n=24) | |||||||
| Baseline |
1.3 |
1.6 |
– |
Baseline |
52.1 (n=24) |
27.0 |
– |
|
| 6 months |
0.8 |
1.1 |
P=0.63 |
6 months |
20.2 (n=23) |
21.2 |
P=0.0002 |
|
| Placebo (n=43) | Placebo (n=43) | |||||||
| Baseline |
1.7 |
2.7 |
– |
Baseline |
52.6 (n=43) |
28.9 |
– |
|
| 6 months |
1.3 |
1.5 |
P=0.63 |
6 months |
43.8 (n=38) |
32.1 |
P=0.2 |
|
| Tender Joint Count (TJC) | Swollen Joint Count (SJC) | |||||||
| Responder (n=36) | Responder (n=36) | |||||||
| Baseline |
11.7 |
13.3 |
– |
Baseline |
10.5 |
11.7 |
– |
|
| 6 months |
2.7 |
6.4 |
p<0.0001 |
6 months |
2.1 |
3.8 |
p<0.0001 |
|
| Nonresponder (n=49) | Nonresponder (n=49) | |||||||
| Baseline |
11.6 (n=49) |
12.8 |
– |
Baseline |
7.7 |
10.6 |
– |
|
| 6 months |
6.4 (n=25) |
10.3 |
P=0.02 |
6 months |
3.8 (n=25) |
6.0 |
P=0.02 |
|
| PP Nonresponder (n=24) | PP Nonresponder (n=24) | |||||||
| Baseline |
13.5 (n=24) |
13.8 |
– |
Baseline |
7.8 (n=24) |
8.1 |
– |
|
| 6 months |
5.8 (n=23) |
9.5(n=23) |
P=0.02 |
6 months |
3.3 (n=23) |
5.3 |
P=0.008 |
|
| Placebo (n=43) | Placebo (n=43) | |||||||
| Baseline |
14.1 (n=43) |
14.8 |
– |
Baseline |
13.2 |
13.7 |
– |
|
| 6 months |
13.1 (n=38) |
15.9 (n=38) |
P=0.5 |
6 months |
10.1 (n=38) |
12.8 |
P=0.2 |
|
| SF-36 Bodily Pain | VAS Pain | |||||||
| Responder (n=36) | Responder (n=36) | |||||||
| Baseline |
41.2 |
26.6 |
– |
Baseline |
44.0 |
26.7 |
– |
|
| 6 months |
65.6 |
25.0 |
P=0.0004 |
6 months |
24.1 |
24.3 |
P=0.003 |
|
| Nonresponder (n=49) | Nonresponder (n=49) | |||||||
| Baseline |
40.4 |
24.3 |
– |
Baseline |
44.4 |
28.7 |
– |
|
| 6 months |
56.8 (n=25) |
25.1 |
P=0.003 |
6 months |
34.6.7 (n=25) |
27.7 |
P=0.2 |
|
| PP Nonresponder (n=24) | PP Nonresponder (n=24) | |||||||
| Baseline |
33.8 (n=23) |
21.2 |
– |
Baseline |
50.25 (n=23) |
30.9 |
– |
|
| 6 months |
57.4 |
21.4 |
P=0.0003 |
6 months |
34.5 |
27.2 |
P=0.08 |
|
| Placebo (n=43) | Placebo (n=43) | |||||||
| Baseline |
35.3 |
23.0 |
– |
Baseline |
53.9 |
28.1 |
– |
|
| 6 months |
35.8 |
21.7 |
P=0.7 |
6 months |
57.2 |
27.6 |
P=0.5 |
|
| SF-36 ASHI | HAQ-DI Functionality Index Scale | |||||||
| Responder (n=36) | Responder (n=36) | |||||||
| Baseline |
55.4 |
29.1 |
– |
Baseline |
1 |
0.8 |
– |
|
| 6 months |
78.8 |
28.3 |
P=0.002 |
6 months |
0.8 |
0.8 |
P=0.20 |
|
| Nonresponder (n=49) | Nonresponder (n=49) | |||||||
| Baseline |
53.6 |
28.3 |
– |
Baseline |
1.2 |
0.9 |
– |
|
| 6 months |
69.7 |
29.1 |
P=0.02 |
6 months |
0.9 |
0.8 |
P=0.20 |
|
| PP Nonresponder (n=24) | PP Nonresponder (n=24) | |||||||
| Baseline |
49.5 |
26.3 |
– |
Baseline |
1.3 |
0.9 |
– |
|
| 6 months |
70.3 |
24.6 |
P=0.004 |
6 months |
0.9 |
0.7 |
P=0.06 |
|
| Placebo (n=43) | Placebo (n=43) | |||||||
| Baseline |
45.8 |
27.3 |
– |
Baseline |
1.2 |
1.0 |
– |
|
| 6 months |
46.6 |
29.0 |
P=1.0 |
6 months |
1.3 |
0.9 |
P=0.7 |
|
| * vs baseline | ||||||||
References
- Lipsky PE, et al. Arthritis Ther Res. 2014;16:R60.
To cite this abstract in AMA style:
Mandell BF, Weisman M, Yeo A, Lipsky PE. Pegloticase Provides Clinical Benefit in Patients with Chronic Refractory Gout Who Did Not Meet the Clinical Trial Biochemical Definition of Response [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pegloticase-provides-clinical-benefit-in-patients-with-chronic-refractory-gout-who-did-not-meet-the-clinical-trial-biochemical-definition-of-response/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/pegloticase-provides-clinical-benefit-in-patients-with-chronic-refractory-gout-who-did-not-meet-the-clinical-trial-biochemical-definition-of-response/