Papers by Brian LaMoreaux
Rheumatology and therapy, Jun 5, 2024
Introduction: Gout, a common comorbidity of chronic kidney disease (CKD), is associated with high... more Introduction: Gout, a common comorbidity of chronic kidney disease (CKD), is associated with high morbidity and healthcare utilization. However, a large proportion of gout remains undermanaged or untreated which may lead to worse patient outcomes and greater healthcare costs. This study estimates the present and future health and economic burden of controlled and uncontrolled gout in a virtual United States (US) CKD population. Methods: A validated microsimulation model was used to project the burden of gout in patients with CKD in the USA through 2035. Databases were utilized to build a virtual CKD population of "individuals" with controlled or uncontrolled gout. Modelling assumptions were made on the basis of the literature, which was sparse in some cases. Health and economic outcomes with the current care (baseline) scenario were evaluated, along with potential benefits of urate-lowering intervention scenarios. Results: The prevalence of comorbid gout and CKD in the USA was projected to increase by 29%, from 7.9 million in 2023 to 9.6 million in 2035 in the baseline scenario. Gout flares, tophi, and comorbidity development were also projected to increase markedly through 2035, with the economic burden of gout in the CKD population subsequently increasing from $38.9 billion in 2023 to $47.3 billion in 2035. An increased use of oral urate-lowering therapies in undermanaged patients, and pegloticase use in patients refractory to oral urate-lowering therapies were also project to result in 744,000 and 353,000 fewer uncontrolled gout cases, respectively, by 2035. Marked reductions in complications and costs ensued. Lise Retat's affiliation has changed since the time of this study. Prior Presentation: Marder B, et al. 2023. Projected benefits of gout control on the health and economic burden of patients with CKD and uncontrolled gout. FR-PO921. Poster presented at the 2023 annual meeting of the American Society of Nephrology (ASN), November 2-5 (Philadelphia, PA). Card-Gowers J, et al. 2023. Present and Future Health and Economic Burden of Controlled and Uncontrolled Gout in Patients with Chronic Kidney Disease in the United States. Poster presented at the European Congress of Rheumatology (EULAR), May 31-June 3 (Milan, Italy).
Journal of the American Society of Nephrology, Nov 1, 2022
Journal of the American Society of Nephrology, Oct 1, 2020
Journal of the American Society of Nephrology, Oct 1, 2021
Annals of the Rheumatic Diseases
BackgroundThere is a strong association between gout and kidney disease due to the kidney’s key r... more BackgroundThere is a strong association between gout and kidney disease due to the kidney’s key role in uric acid excretion.1-4 Several studies have also demonstrated that serum uric acid is an independent risk factor for decline in renal function1,2. There are little national data available regarding the clinical burden of kidney disease in gout patients in the US.ObjectivesTo estimate the percentage of US hospitalizations with a concomitant diagnosis of gout and either acute or chronic kidney disease compared with percentage of hospitalizations with kidney disease in the general population.MethodsThe Nationwide Inpatient Sample (NIS) is a stratified random sample of all US community hospitals. It is the only US national hospital database with information on all patients, regardless of payer, including persons covered by Medicare, Medicaid, private insurance, and the uninsured. Detailed information including clinical and nonclinical data elements on each hospital stay including Int...
Arthritis research & therapy, Apr 12, 2024
Background/Purpose Little is known about long-term clinical outcomes or urate-lowering (ULT) ther... more Background/Purpose Little is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU), inflammatory biomarkers, and renal function following pegloticase discontinuation. Methods We conducted a retrospective analysis of gout patients who discontinued pegloticase using the Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 to 6/2022. We defined discontinuation as a gap ≥ 12 weeks after last infusion. We examined outcomes beginning two weeks after last dose and identified ULT therapy following pegloticase discontinuation. We evaluated changes in lab values (SU, eGFR, CRP and ESR), comparing on-treatment (≤ 15 days of the second pegloticase dose) to post-treatment. Results Of the 375 gout patients discontinuing pegloticase, median (IQR) laboratory changes following discontinuation were: SU: +2.4 mg/dL (0.0,6.3); eGFR:-1.9 mL/min (− 8.7,3.7); CRP:-0.8 mg/L (-12.8,0.0); and ESR:-4.0 mm/hr (-13.0,0.0). Therapy post-discontinuation included oral ULTs (86.0%), restarting pegloticase (4.5%), and no documentation of ULT (9.5%), excluding patients with multiple same-day prescriptions (n = 17). Oral ULTs following pegloticase were: 62.7% allopurinol, 34.1% febuxostat. The median (IQR) time to starting/restarting ULT was 92.0 days (55.0,173.0). Following ULT prescribing (≥ 30 days), only 51.0% of patients had SU < 6 mg/dL. Patients restarting pegloticase achieved a median SU of 0.9 mg/dL (IQR:0.2,9.7) and 58.3% had an SU < 6 mg/dL. Conclusion Pegloticase treats uncontrolled gout in patients with failed response to xanthine oxidase inhibitors, but among patients who discontinue, optimal treatment is unclear. Based on this analysis, only half of those starting another ULT achieved target SU. Close follow-up is needed to optimize outcomes after pegloticase discontinuation. Rheumatology key messages • Information about gout treatment following pegloticase discontinuation is limited. We found that after discontinuing pegloticase, patients frequently used oral ULTs (86% of those discontinuing pegloticase).
ACR open rheumatology, Jun 29, 2023
ObjectiveTo assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus peglot... more ObjectiveTo assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]).MethodsPatients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level &lt;6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values.ResultsMonth 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks.ConclusionTwelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect.
Background: Pegloticase is a PEGylated recombinant uricase approved in the US for treating adult ... more Background: Pegloticase is a PEGylated recombinant uricase approved in the US for treating adult patients with chronic refractory gout. As a biologic medication, pegloticase is administered intravenously every 2 weeks. It is currently not known whether a gap in the standard biweekly regimen can be tolerated or would be associated with a loss of efficacy. During the pivotal trial testing of pegloticase, some patients experienced a delay between participation in the randomized controlled trial (RCT) and the open-label extension (OLE) that followed. Analysis of the clinical impact of this gap was carried out to understand whether therapeutic benefit would be affected. Objectives: The objective of this analysis was to determine, among pegloticase responders, the effect of a 28 or more day gap between doses of pegloticase on the subsequent urate lowering response and frequency of infusion reactions. Methods: These analyses utilized results from two RCTs of pegloticase and a 2-year OLE. In the RCTs, 36 of 85 patients, who were dosed with pegloticase every two weeks, were classified as responders (persistent urate lowering during intensive monitoring at 3 and 6 months of the RCT), and went on to enroll in the OLE and receive additional doses of pegloticase. Of these 36 patients, 14 had a gap between pegloticase doses of more than 28 days. Results: Among the 14 patients with a gap of more than 28 days between doses of pegloticase therapy the length of the gap ranged from 34 to 167 days (mean =72.5 days, median =59.5 days). Of these 14 patients, 8 received pegloticase on an every-4-week dosing schedule in the OLE and 6 remained on every-2-week dosing. Ten of the 14 patients maintained their serum urate level <6mg/dL in the OLE. Five of 6 that remained on every 2 week dosing and 5 of 8 that went to every 4 week dosing continued to have serum urate <6mg/dL. (see table 1). By logistic regression analysis, the length of the gap had no significant effect on the subsequent urate lowering effect of pegloticase. Of the fourteen patients with a gap in pegloticase therapy, 2 (14%) had infusion reactions during a total of 632 infusions in the OLE yielding a re-treatment IR rate of 0.32%.
Rheumatology and therapy, May 3, 2018
Introduction: Pegloticase, a potent uricolytic biologic enzyme, has been shown to be an effective... more Introduction: Pegloticase, a potent uricolytic biologic enzyme, has been shown to be an effective therapeutic option in patients with uncontrolled gout. However, there are limited data on clinical response after a gap in therapy and retreatment with pegloticase. Case Series: This report describes four patients with chronic gout who were successfully managed with pegloticase and were retreated following a gap in therapy. Patient charts from a practice-based rheumatology clinic were retrospectively analyzed; four male patients, aged 70-75 years, with chronic gout and a more than 4-week gap in pegloticase therapy were reviewed. Before pegloticase treatment, patients had received allopurinol or febuxostat, but they continued exhibiting symptoms, including visible tophi and serum uric acid (SUA) levels of 5.2-10.2 mg/dL (309-607 lmol/L), despite oral urate-lowering therapy. The first pegloticase treatment (8-mg infusion every 2 weeks) lasted 22-124 weeks. Pegloticase resolved tophi and improved SUA to below 1.5 mg/dL (less than 89 lmol/L); however, patients discontinued pegloticase because of symptom resolution, poor adherence, or personal reasons. Following treatment gaps (12-156 weeks), symptoms and SUA levels increased and patients were retreated with pegloticase (4-147 weeks). In three of four patients, reinitiating pegloticase lowered SUA levels to below 1.0 mg/dL (less than 59 lmol/L) and resolved symptoms. One patient experienced an infusion reaction and discontinued; no infusion reactions, gout flares, or adverse events occurred among the other three patients. Conclusion: Retreatment with pegloticase after a gap in therapy appears to be an effective and tolerated option in prior responders. Funding: Horizon Pharma.
Annals of Transplantation, Apr 14, 2020
Research funding provided by Horizon Pharma Background: Kidney transplantation is associated with... more Research funding provided by Horizon Pharma Background: Kidney transplantation is associated with increased prevalence of gout. However, evidence of the effect of gout on long-term kidney transplantation outcomes is mixed. This study examined mortality risk among patients with a history of kidney transplantation with vs. without gout. Material/Methods: A retrospective study was conducted using Medicare Fee-for-Service administrative claims of patients with a history of kidney transplantation. Cox proportional hazards models determined the effect of gout on all-cause mortality, controlling for confounders, including comorbid mortality risk, via the Charlson Comorbidity Index. Because the relationships between gout and components of the Charlson Comorbidity Index are also debated, 3 different model assumptions were used: 1) gout shares a common cause with these comorbidities, 2) gout is upstream of these comorbidities, 3) the effect of gout on mortality is modified by these comorbidities. Results: Gout increased the risk of all-cause mortality in the unadjusted model (hazard ratio: 1.44, 95% CI 1.27-1.63) and after adjustment for demographics and transplant vintage (hazard ratio: 1.16, 95% CI 1.02-1.32). Gout was not a significant risk after adjustment for baseline Charlson Comorbidity Index (hazard ratio: 1.03, 95% CI 0.90-1.17). Gout was associated with greater mortality among patients without baseline comorbidities (Charlson Comorbidity Index=0; hazard ratio: 3.48, 95% CI 1.27-9.57) in the stratified model. Conclusions: Among patients with a history of kidney transplantation, gout did not have an independent effect on all-cause mortality. However, gout was a predictor of mortality among patients with no comorbidities, suggesting that gout is an early warning sign of poor health in kidney transplantation patients.
Pediatric Rheumatology, Jun 26, 2018
Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology,... more Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Methods: Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, − 50, − 70, − 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Results: Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, − 50, − 70, and − 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect.
AB1084-Table 1 Calprotectin (mg/mL) (range) PCR (mg/dL) (range) ESR (mmHg) (range)
Current Rheumatology Reports, Nov 24, 2020
Purpose of Review Medical treatment with urate-lowering therapy (ULT) is efficacious. A recent pu... more Purpose of Review Medical treatment with urate-lowering therapy (ULT) is efficacious. A recent publication suggested that surgery in gout is more prevalent than previously reported. This revelation led us to review what is known about surgical treatment of gout. Recent Findings The Google Scholar database (January 1, 2014-January 1, 2020) found 104 publications with a total of 169 gout patients, with an average disease duration of 6.7 years. Most (68%) were not on ULT. The mean pre-operative serum urate levels were 9.19 mg/dL. One hundred thirteen patients underwent tophi excision, while in 33 patients, tophi were found during surgery. The majority of the surgeries were performed in Asia and Europe. Summary Most patients were not taking ULT at the time of surgery, leading to hyperuricemia. This can result in tophi reformation post-surgery. The role of surgery should be a last-line treatment and until recently has only been demonstrated through case reports.
Annals of the Rheumatic Diseases, May 23, 2022
homozygous CC genotype and CA or AA genotypes did not differ: 17 (33%) and 11 (35%) cases, respec... more homozygous CC genotype and CA or AA genotypes did not differ: 17 (33%) and 11 (35%) cases, respectively. It turned out that CA and AA pts required a significantly higher dose of allopurinol (365±102 mg/day) than CC pts (290±85 mg/day), p=0.002. Of 54 pts treated with febuxostat who did not achieve the target sUA level, 30 (56%) pts had the CC genotype and 24 (44%) pts had the CA genotype. The opportunity of the target sUA level achievement was comparable (p=0.22). Conclusion: The opportunity of achieving the target sUA level in pts with gout taking allopurinol is not associated with the C>A polymorphism of the ABCG2 gene, but the presence of the CA and AA genotypes is associated with the need to prescribe large doses of allopurinol. REFERENCES: [1] Wen CC, Yee SW, Liang X et al. Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response.
Annals of the Rheumatic Diseases, May 23, 2022
Background: Primary synovial chondromatosis (prSynCh) is a metaplastic disorder of the synovial m... more Background: Primary synovial chondromatosis (prSynCh) is a metaplastic disorder of the synovial membrane, characterized by chondrocyte differentiation of synovial pluripotent stem cells, and chondroid tissue production. The prSynCh may be accompanied with amorphous calcium phosphate or carbonate deposition and bone formation, with or without true medullary spaces. The cause of stem cell differentiation is unknown; different irritative agents (infective, toxic, mechanic, etc.) are mentioned, but the condition may occur spontaneously as well [1, 2]. Crystal deposits as irritative agents of primary synovial chondromatosis due to a clinically latent metabolic disorder are not mentioned. Objectives: The aim of this study was to determine the formal pathogenesis of synovial chondromatosis, and to detect crystal deposits in synovial membrane in order to explore the possible role of metabolic diseases in transformation of stem cells into chondrocytes, i.e., to demonstrate the metabolic origin of prSynCh. Methods: Surgical specimens (synovial membranes of 14 knees, 4 hips and 2 elbows) of 20 patients (females 13. mean age of 50.17 years, range 40-74; males 7, mean age of 40.64 years, range 30-76years) with primary synovial chondromatosis were studied histologically. Cases of secondary synovial chondromatosis, i.e., due to osteoarthritis, rheumatoid arthritis, aseptic (avascular) bone necrosis, osteochondral traumatic injury, etc. were excluded. Serial sections (5 microns) of tissue samples were stained with HE , Alizarin red S (specific for calcium), and von Kossa's reaction (specific for phosphate and/or carbonate), and were compared with unstained sections according to Bély and Apáthy (2013). The non-staining technique is a very sensitive method to detect small crystals with weak birefringence viewed under polarized light [3-5]. Results: Chondromatosis (chondroid formation without osteoid or bone formation) was found in 8, osteochondromatosis (chondroid with osteoid and bone formation) in 11, and only bone formation in 1 of 20 patients. True medullary spaces accompanied bone formation in 8 of 12 cases. Different stages of chondroid and/or bone formation existed side by side in the same histologic section. In non-stained sections HA [Ca 5 (PO 4) 3 (OH)], CPPD [Ca 2 P 2 O 7 .2H 2 O] crystals, and/ or unidentified crystal fragments were detected in all cases. Amorphous calcium phosphate and/or carbonate deposits were present in 12 of 20 patients.
Annals of the Rheumatic Diseases, Jun 1, 2020
Objectives: This study aimed to evaluate the association of serum vitamin A, vitamin E and folate... more Objectives: This study aimed to evaluate the association of serum vitamin A, vitamin E and folate level with hyperuricemia in the Korean general population. Methods: The present study included 6023 participants (2722 men and 3301 women) aged ≥19 years with available data on serum vitamin A, vitamin E, folate and serum uric acid. General characteristics of participants were compared using the Chi-square test and Student's t test. The association between serum vitamin A, E and folate and serum uric acid levels were evaluated using general linear regression model. Multivariate logistic regression analyses were performed to estimate the effects of these micronutrients on hyperuricemia. Results: Serum uric acid levels were increased from the lowest quintile of vitamin A levels to the highest quintile after adjustment for covariates (P trend < 0.001 in both sexes). In addition, dose-dependent relationship was observed between vitamin A levels and the risk of hyperuricemia in fully-adjusted analyses (P trend < 0.001 in both sexes). However, neither serum vitamin E nor serum folate was associated with hyperuricemia across analyses models. Conclusion: This study suggested that vitamin A could be a risk factor of hyperuricemia and further studies are warranted to elucidate underlying mechanism of the observed findings. References: [1] Choi, Woo-Joo, et al. "Independent association of serum retinol and βcarotene levels with hyperuricemia: A national population study." Arthritis care & research 64.3 (2012): 389-396.
Annals of the Rheumatic Diseases, Jun 1, 2020
Transplantation Proceedings, Dec 1, 2019
Purpose. Although incidence and survival are frequent topics within the solid organ transplantati... more Purpose. Although incidence and survival are frequent topics within the solid organ transplantation (SOT) literature, the size of the surviving SOT population is not well known. Existing studies of gout in patients with SOT have focused on the incident SOT population. This analysis was performed to characterize the prevalent SOT population and the prevalence of gout within it. Methods. This study includes the 2017 United States (US) population size of recipients of kidney, heart, liver, and lung transplants that was estimated by combining primary transplant recipient cohort sizes (1988-2017) with previously published survival rates for each annual cohort's time since transplantation (0-29 years). Gout among prevalent patients with SOT was assessed using Medicare and commercial claims. Results. A total of 637,231 US patients received a primary kidney (393,953), liver (142,186), heart (66,637), or lung (34,455) transplant between 1988 and 2017. An estimated 356,000 (55.8%) recipients were alive in 2017 (233,000 kidney; 78,700 liver; 29,300 heart; 14,700 lung). Gout was identified in 11% of prevalent patients with SOT in 2016. Higher rates of gout were seen in recipients of kidney (13.1%) and heart (12.7%) compared to recipients of liver (6.7%) and lung (5.6%) (P < .0001 in both datasets). Active diagnosed gout prevalence in the US population without a SOT history was 1.1% in 2016. Conclusions. Hundreds of thousands of US patients are living with a transplanted organ today and these numbers are likely to increase. In patients with SOT, gout is a frequent comorbidity of which physicians should be aware. This study suggests a markedly higher rate of gout among transplant recipients compared to the general US population. S OLID organ transplantation (SOT) was a dramatic therapeutic advance of the 20th century that provided patients with numerous clinical benefits, including significantly extended longevity [1e3]. The first successful kidney transplantation was performed in the United States in 1954, but the procedure remained relatively uncommon for several decades due to limited organ availability and high rates of rejection [1]. Over time, the list of feasible Research funding provided by Horizon Pharma. The sponsor was involved in the study design, writing of the report, and in the decision to submit the article for publication via authors employed by Horizon Pharma.
Annals of the Rheumatic Diseases, May 23, 2022
Annals of the Rheumatic Diseases, May 23, 2022
homozygous CC genotype and CA or AA genotypes did not differ: 17 (33%) and 11 (35%) cases, respec... more homozygous CC genotype and CA or AA genotypes did not differ: 17 (33%) and 11 (35%) cases, respectively. It turned out that CA and AA pts required a significantly higher dose of allopurinol (365±102 mg/day) than CC pts (290±85 mg/day), p=0.002. Of 54 pts treated with febuxostat who did not achieve the target sUA level, 30 (56%) pts had the CC genotype and 24 (44%) pts had the CA genotype. The opportunity of the target sUA level achievement was comparable (p=0.22). Conclusion: The opportunity of achieving the target sUA level in pts with gout taking allopurinol is not associated with the C>A polymorphism of the ABCG2 gene, but the presence of the CA and AA genotypes is associated with the need to prescribe large doses of allopurinol. REFERENCES: [1] Wen CC, Yee SW, Liang X et al. Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response.
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Papers by Brian LaMoreaux