PMID- 33750034
OWN - NLM
STAT- MEDLINE
DCOM- 20210908
LR  - 20220802
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 73
IP  - 8
DP  - 2021 Aug
TI  - Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate 
      Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double-Blind, 
      Placebo-Controlled Trial.
PG  - 1523-1532
LID - 10.1002/art.41731 [doi]
AB  - OBJECTIVE: Pegloticase is used for the treatment of severe gout, but its use is 
      limited by immunogenicity. This study was undertaken to evaluate whether 
      mycophenolate mofetil (MMF) prolongs the efficacy of pegloticase. METHODS: 
      Participants were randomized 3:1 to receive 1,000 mg MMF twice daily or placebo 
      for 14 weeks, starting 2 weeks before receiving pegloticase and continuing while 
      receiving intravenous pegloticase 8 mg biweekly for 12 weeks. Participants then 
      received pegloticase alone from week 12 to week 24. The primary end points were 
      the proportion of patients who sustained a serum urate level of </=6 mg/dl at 12 
      weeks and the rate of adverse events (AEs). Secondary end points included 24-week 
      durability of serum urate level </=6 mg/dl. Fisher's exact test and Wilcoxon's 
      2-sample test were used for analyses, along with Kaplan-Meier estimates and log 
      rank tests. RESULTS: A total of 32 participants received >/=1 dose of pegloticase. 
      Participants were predominantly men (88%), with a mean age of 55.2 years, mean 
      gout duration of 13.4 years, and mean baseline serum urate level of 9.2 mg/dl. At 
      12 weeks, a serum urate level of </=6 mg/dl was achieved in 19 (86%) of 22 
      participants in the MMF arm compared to 4 (40%) of 10 in the placebo arm (P = 
      0.01). At week 24, the serum urate level was </=6 mg/dl in 68% of MMF-treated 
      patients versus 30% of placebo-treated patients (P = 0.06), and rates of AEs were 
      similar between groups, with more infusion reactions occurring in the placebo arm 
      (30% versus 0%). CONCLUSION: Our findings indicate that MMF therapy with 
      pegloticase is well tolerated and shows a clinically meaningful improvement in 
      targeted serum urate level of </=6 mg/dl at 12 and 24 weeks. This study suggests an 
      innovative approach to pegloticase therapy in gout.
CI  - (c) 2021, American College of Rheumatology.
FAU - Khanna, Puja P
AU  - Khanna PP
AUID- ORCID: 0000-0002-0264-1317
AD  - University of Michigan, Ann Arbor.
FAU - Khanna, Dinesh
AU  - Khanna D
AUID- ORCID: 0000-0003-1412-4453
AD  - University of Michigan, Ann Arbor.
FAU - Cutter, Gary
AU  - Cutter G
AD  - University of Alabama at Birmingham.
FAU - Foster, Jeff
AU  - Foster J
AD  - University of Alabama at Birmingham.
FAU - Melnick, Joshua
AU  - Melnick J
AD  - University of Alabama at Birmingham.
FAU - Jaafar, Sara
AU  - Jaafar S
AD  - University of Michigan, Ann Arbor.
FAU - Biggers, Stephanie
AU  - Biggers S
AD  - University of Alabama at Birmingham.
FAU - Rahman, A K M Fazlur
AU  - Rahman AKMF
AD  - University of Alabama at Birmingham.
FAU - Kuo, Hui-Chien
AU  - Kuo HC
AD  - University of Alabama at Birmingham.
FAU - Feese, Michelle
AU  - Feese M
AD  - University of Alabama at Birmingham.
FAU - Kivitz, Alan
AU  - Kivitz A
AD  - Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.
FAU - King, Charles
AU  - King C
AD  - North Mississippi Medical Center, Tupelo.
FAU - Shergy, William
AU  - Shergy W
AD  - Rheumatology Associates of North Alabama, Huntsville.
FAU - Kent, Jeff
AU  - Kent J
AD  - Horizon Therapeutics, Lake Forest, Illinois, USA.
FAU - Peloso, Paul M
AU  - Peloso PM
AD  - Horizon Therapeutics, Lake Forest, Illinois, USA.
FAU - Danila, Maria I
AU  - Danila MI
AUID- ORCID: 0000-0001-9246-6200
AD  - University of Alabama at Birmingham.
FAU - Saag, Kenneth G
AU  - Saag KG
AD  - University of Alabama at Birmingham.
LA  - eng
SI  - ClinicalTrials.gov/NCT03303989
GR  - K24 AR063120/AR/NIAMS NIH HHS/United States
GR  - R21 AR071684/AR/NIAMS NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20210519
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Gout Suppressants)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 1.7.3.3 (Urate Oxidase)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - R581OT55EA (Pegloticase)
SB  - IM
MH  - Adaptive Immunity/*drug effects
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Gout/*drug therapy/immunology
MH  - Gout Suppressants/*administration & dosage/immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/*administration & dosage/immunology
MH  - Polyethylene Glycols/*administration & dosage
MH  - Proof of Concept Study
MH  - Treatment Outcome
MH  - Urate Oxidase/*administration & dosage/immunology
PMC - PMC8324571
MID - NIHMS1683488
EDAT- 2021/03/23 06:00
MHDA- 2021/09/09 06:00
PMCR- 2022/08/01
CRDT- 2021/03/22 13:05
PHST- 2021/02/18 00:00 [revised]
PHST- 2020/10/16 00:00 [received]
PHST- 2021/03/09 00:00 [accepted]
PHST- 2021/03/23 06:00 [pubmed]
PHST- 2021/09/09 06:00 [medline]
PHST- 2021/03/22 13:05 [entrez]
PHST- 2022/08/01 00:00 [pmc-release]
AID - 10.1002/art.41731 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2021 Aug;73(8):1523-1532. doi: 10.1002/art.41731. Epub 2021 
      May 19.