PMID- 34997911
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220602
IS  - 2198-6576 (Print)
IS  - 2198-6584 (Electronic)
IS  - 2198-6576 (Linking)
VI  - 9
IP  - 2
DP  - 2022 Apr
TI  - Effect of Leflunomide on Pegloticase Response Rate in Patients with Uncontrolled 
      Gout: A Retrospective Study.
PG  - 555-563
LID - 10.1007/s40744-021-00421-w [doi]
AB  - BACKGROUND: Pegloticase, a PEGylated uricase for uncontrolled gout, rapidly 
      lowers serum urate (SU). Not all patients complete a full-therapy course because 
      anti-pegloticase antibodies can develop, causing efficacy loss and infusion 
      reactions. The literature and clinical trial data indicate that methotrexate 
      co-administration markedly improves pegloticase response rates from the 
      established monotherapy response rate of 42%. Unfortunately, methotrexate use is 
      restricted by kidney disease, which is often present in uncontrolled gout 
      patients. Leflunomide is less restricted in patients with renal dysfunction. This 
      study examined the treatment response rate of pegloticase co-administered with 
      leflunomide. METHODS: Patients co-treated with pegloticase (8 mg biweekly 
      infusion) and oral leflunomide (20 mg/day) were included. Patient/treatment 
      characteristics and safety parameters (adverse events [AEs], laboratory 
      parameters) were examined. Pre-infusion prophylaxis was administered (day of 
      infusion: IV solumedrol, night before and morning of infusion: oral fexofenadine 
      or diphenhydramine). Patients were considered treatment responders if >/= 12 
      pegloticase infusions were administered and pre-infusion SU < 6 mg/dl at 
      infusion-12. RESULTS: Ten patients (five male, 72.7 +/- 12.5 years) were included. 
      The most common comorbidities were chronic kidney disease (90%), hypertension 
      (70%), diabetes mellitus (60%), obesity (60%), and congestive heart failure 
      (50%). Baseline SU was 7.1 +/- 2.4 mg/dl and nine patients (90%) had subcutaneous 
      tophi noted. Seven patients (70%) met responder criteria, receiving 26.6 +/- 14.0 
      infusions (range 13-55) with a pre-infusion-12 SU of 0.9 +/- 1.5 mg/dl. The three 
      non-responders received < 12 infusions because of unrelated AEs or loss of 
      follow-up. Three patients (30%) experienced AEs. One had unrelated cardiac 
      disease worsening and three gout flares, one had a pre-infusion solumedrol 
      reaction (wooziness/loss of consciousness), and one had two mild, transient 
      increases in liver enzymes. CONCLUSIONS: This study supports leflunomide as 
      co-therapy to pegloticase in uncontrolled gout patients. Heterogeneity and high 
      comorbidity burden in uncontrolled gout patients makes having a variety of 
      immunomodulators options important.
CI  - (c) 2022. The Author(s).
FAU - Masri, Karim Richard
AU  - Masri KR
AD  - Bon Secours Rheumatology Center, Richmond, VA, USA.
FAU - Padnick-Silver, Lissa
AU  - Padnick-Silver L
AD  - Horizon Therapeutics, Lake Forest, IL, USA.
FAU - Winterling, Kevin
AU  - Winterling K
AD  - Horizon Therapeutics, Lake Forest, IL, USA.
FAU - LaMoreaux, Brian
AU  - LaMoreaux B
AUID- ORCID: 0000-0001-7521-241X
AD  - Horizon Therapeutics, Lake Forest, IL, USA. blamoreaux@horizontherapeutics.com.
AD  - , 1 Horizon Way, Deerfield, IL, 600615, USA. blamoreaux@horizontherapeutics.com.
LA  - eng
PT  - Journal Article
DEP - 20220108
PL  - England
TA  - Rheumatol Ther
JT  - Rheumatology and therapy
JID - 101674543
PMC - PMC8964845
OTO - NOTNLM
OT  - Immunomodulation
OT  - Leflunomide
OT  - Pegloticase
OT  - Refractory gout
OT  - Uncontrolled gout
EDAT- 2022/01/09 06:00
MHDA- 2022/01/09 06:01
PMCR- 2022/01/08
CRDT- 2022/01/08 12:07
PHST- 2021/11/16 00:00 [received]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2022/01/09 06:00 [pubmed]
PHST- 2022/01/09 06:01 [medline]
PHST- 2022/01/08 12:07 [entrez]
PHST- 2022/01/08 00:00 [pmc-release]
AID - 10.1007/s40744-021-00421-w [pii]
AID - 421 [pii]
AID - 10.1007/s40744-021-00421-w [doi]
PST - ppublish
SO  - Rheumatol Ther. 2022 Apr;9(2):555-563. doi: 10.1007/s40744-021-00421-w. Epub 2022 
      Jan 8.