Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Use of Pegloticase in Chronic Gout Refractory to Conventional Therapy Is Associated with Significant Clinical Benefit: Tender Joint and Swollen Joint Counts and Patient Global Assessment (Health Assessment Questionnaire).

Mandel3,  David R., Baraf1,  Herbert, Rehrig5,  Claudia, Horowitz6,  Zebulun D., Ottery4,  Faith D., Yood2,  Robert A.

Arthritis & Rheumatism Association, Wheaton, MD
Fallon Clinic, Worcester, MA
Private Practive, Mayfield Village, OH
Savient Pharmaceuticals, Inc
Savient Pharmaceuticals, Inc.
Savient Pharmaceuticals, Inc., Baskingridge, NJ

Purpose:

To assess the therapy response of pegloticase for a spectrum of non-flare, non-tophus, gout-related rheumatologic variables in patients (pts) with treatment refractory chronic gout (TRCG) in 2 replicate Phase 3, randomized, double-blind, placebo-controlled trials (RCTs).

Methods:

TRCG was defined as: >=3 flares in the previous 18 months, or >=1 tophus, or gouty arthropathy; serum urate >8.0 mg/dL; and prior failure of maximum medically appropriate dose of allopurinol or contraindication to allopurinol. 212 pts were treated with IV pegloticase or placebo (PBO) in the Phase 3 RCTs. Pts were randomized to PGL 8 mg q2wk (n=85), 8 mg q4wk (n=84), or PBO (n=43) and were infused every 2 weeks for 6 months in a blinded fashion. Primary response endpoint was plasma uric acid (PUA) <6.0 mg/dL 80% of the time in months 3 and 6. Data were pooled for secondary endpoints: reduction of tophus size, gout flare incidence, swollen joints (SJ), tender joints (TJ), pt-reported outcomes by SF-36 and Health Assessment Questionnaire (HAQ). Change from baseline for each secondary rheumatologic variable was compared by regimen and PUA responder status.

Results:

Baseline characteristics: 82% male; mean age 55 yrs; high degree of comorbidity: hypertension (71%), chronic kidney disease (43%), cardiovascular disease (31%), and diabetes (22%). As previously reported at ACR 2008, both pegloticase groups were significantly superior to PBO for the primary efficacy endpoint in both studies. Tender joint or swollen joint counts (Table 1) and HAQ-Patient Global Assessment (Table 2), assessed for change from baseline to last visit (last observation carried forward) or week 25, were significant for pooled PGL vs PBO (<=0.001). Changes within each pegloticase group were consistently better in PUA responders® vs non-responders (NR).

Table 1. Tender Joint and Swollen Joint Counts

Swollen Joint CountPeglotlcase q2wkPeglotlcase q4wkPlacebo
 RNRTotalRNRTotal 
Baseline, n36498429548343
Baseline, mean (SD)10.5 (11.7)7.7 (10.6)8.9 (11.1)10.3 (11.5)9.9 (9.2)10.1 (10.0)13.2 (13.7)
Week 25, n36256129346338
Week 25, mean D(SD)-8.6 (10.3)-3.4 (9.4)-6.4 (10.2)-8.0 (9.3)-3.4 (5.3)-5.6 (7.78)-2.1 (12.2)
Final visit, n35437829487743
Final visit, mean D(SD)-8.6 (10.3)-3.0 (10.0)**-6.5 (10.5)-8.0 (9.3)-3.3 (6.20)**-6.1 (7.8)-2.6 (11.6)
p-value [1]      0.001
Tender Joint CountPeglotlcase q2wkPeglotlcase q4wkPlacebo
 RNRTotalRNRTotal 
Baseline, n36498429548343
Baseline, mean (SD)11.7 (13.3)11.6 (12.8)11.7 (13.0)12.3 (15.3)10.4 (12.6)11.1 (13.5)14.1 (14.8)
Week 25, n36256129346338
Week 25, mean D(SD)-8.9 (12.0)-7.7 (12.1)-8.4 (11.9)-9.9 (12.8)-3.9 (8.89)-6.7 (11.2)-0.9 (12.8)
Final visit, n35437829487743
Final visit, mean D(SD)-8.9 (12.0)-6.1 (11.9)**-7.4 (12.0)*-9.9 (12.8)-3.9 (8.5)**-6.1 (10.6)*-1.2 (12.3)
p-value [1]      <0.001
Week 25 = 14 days after dose 12[1]P-value for pooled PGL vs PBO.*P-value significant or comparison of corresponding peglotlcase group vs. placebo.**P-value significant or comparison of with in group P vs. NR

Table 2. HAQ Patient Global Assessment

 Pegloticase q2wkPeglotlcase q4wkPlacebo
 RNRTotalRNRTotal 
Baseline, n33407325537840
Baseline, mean (SD)42.7 (26.1)42.2 (24.0)42.4 (24.8)49.6 (25.2)49.9 (25.0)49.8 (24.9)51.6 (24.9)
Week 25, n32205225335835
Week 25, mean (SD)23.3 (20.7)33.1 (24.6)27.1 (2.6)26.2 (19.6)41.4 (26.3)34.9 (24.7)53.4 (25.5)
A from BL-20.0 (27.0)-13.2 (21.1)**-17.5 (24.9)*-23.4 (24.8)-6.2 (23.7)**-13.6 (25.5)*4.2 (20.2)
P-value [1]      <0.001
Final visit, n3336*6925477240
Final visit, mean (SD)22.8 (20.7)37.5 (27.2)30.4 (25.2)26.2 (19.6)42.9 (25.3)37.1 (24.7)52.4 (26.2)
A from BL-19.94 (26.5)-4.2 (27.6)**-11.9 (28.0)*-23.4 (24.8)-6.9 (26.6)**-12.6 (27.0)*0.8 (25.0)
P-value [1]      <0.001
[1] P-value for pooled PGL vs PBO.*P-value significant for comparison of corresponding pegloticase group vs. placebo**P-value significant for comparison of within group R vs. NR§Change from baseline only includes 19 (or 35) subjects based on lacking baseline for one subject

Conclusions:

Successful pegloticase therapy in patients with chronic gout refractory to conventional urate-lowering therapy (defined as UA < 6 mg/dL 80% of the time in months 3 and 6 during replicate Phase 3 trials), is associated with improvement in tender joint and swollen joint counts and Patient Global Assessment.

To cite this abstract, please use the following information:
Mandel, David R., Baraf, Herbert, Rehrig, Claudia, Horowitz, Zebulun D., Ottery, Faith D., Yood, Robert A.; Use of Pegloticase in Chronic Gout Refractory to Conventional Therapy Is Associated with Significant Clinical Benefit: Tender Joint and Swollen Joint Counts and Patient Global Assessment (Health Assessment Questionnaire). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :166
DOI: 10.1002/art.27935

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