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Nicola Dalbeth - One of the best experts on this subject based on the ideXlab platform.

  • AB1058 Time to resolution of tophi with urate lowering agents: A literature analysis of randomized trials
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Michael Becker, Fernando Perez-ruiz, R. Yood, Nicola Dalbeth
    Abstract:

    Background The tophus is a pathognomonic feature of chronic gout and may cause disability and joint damage. Accordingly, OMERACT has endorsed tophus measurement as a key domain in clinical trials of chronic gout. The approval of febuxostat (FEB) in 2009 and pegloticase (PGL) in 2010 has been accompanied by publications describing clinical trials of urate-lowering therapies (ULTs). These trials also provide detailed data, not previously available, on change in tophus burden in response to treatment in defined gout populations. Objectives We compared tophus resolution in published clinical trials of ULTs that included such measurements. Methods A PubMed search using the terms “gout” and “tophi OR tophus” was performed with the following limits applied: clinical trial, humans, and English. The 15 articles retrieved were evaluated for appropriateness and used to identify additional publications/abstracts. Six trials met the analysis criteria. Results Conclusions Clinical trials of ULTs have not used consistent methods or timepoints to evaluate tophus response. Nevertheless, pegloticase treatment results in more robust and rapid resolution of tophi compared to treatment with febuxostat or allopurinol. References Wallace et al. Arth Rheum 1977;20:895-900. Disclosure of Interest M. Becker Grant/Research support from: Savient, Takeda, Consultant for: Savient, Takeda, Ardea, BioCryst, Regeneron, URL/Mutual/Metabolex/Chugai, R. Yood Grant/Research support from: Savient, Takeda, F. Perez-Ruiz Consultant for: Ardea, Menarini, Novartis, Savient, Speakers Bureau: Ardea, Menarini, Novartis, Savient, N. Dalbeth Grant/Research support from: Fonterra, Consultant for: Takeda, Ardea, Novartis, Abbott, Roche

  • Review: Gout: A Roadmap to Approaches for Improving Global Outcomes.
    Arthritis & Rheumatism, 2016
    Co-Authors: Nicola Dalbeth, Hyon K. Choi, Robert Terkeltaub
    Abstract:

    Gout: A roadmap to approaches for improving global outcomes Nicola Dalbeth 1 *, Hyon K. Choi 2 *, Robert Terkeltaub 3 *contributed equally to this manuscript Nicola Dalbeth MB ChB, MD, Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz Hyon K. Choi, MD, PhD, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA hchoi@mgh.harvard.edu Robert Terkeltaub, MD, VA San Diego Healthcare System, San Diego, CA, Dept. of Medicine, University of California San Diego, San Diego, CA rterkeltaub@ucsd.edu Supported by the Health Research Council of New Zealand (9101-3708025)(ND), NIH (R01AR065944)(HKC), and VA Research Service (RT). Dr. Dalbeth has received grant support from AstraZeneca and has participated on speaker bureaus for Menarini, ARDEA/Astra-Zeneca, Takeda, and as a consultant for Astra-Zeneca, Fonterra, Takeda, Pfizer, CymaBay, and Crealta. Dr. Choi has served as consultant for Takeda and ARDEA/Astra-Zeneca. Dr. Terkeltaub has served as a consultant for ARDEA/Astra-Zeneca, SOBI, Revive, Selecta, Aequus, ProteoThera, Horizon, Relburn, and CymaBay. Correspondence to: Robert Terkeltaub MD, VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, CA 92161. Telephone: 858 642 3519. Fax: 858 552 7425, email: rterkeltaub@ucsd.edu Running Head: Roadmap to improved gout outcomes Keywords: Hyperuricemia, ABCG2, URAT1, NLRP3 inflammasome, Precision Medicine

  • THU0537 Clinical Response of Tophus and Flares To Extended Use of Lesinurad in Combination with A Xanthine Oxidase Inhibitor in Patients with Gout
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Thomas Bardin, Nicola Dalbeth, C. Storgard, Robert Terkeltaub, Maple Fung, J Hu, Fernando Perez-ruiz
    Abstract:

    Background Three randomized, double-blind, Phase III trials reported that greater proportions of patients treated with lesinurad 200 mg (LESU200) or 400 mg (LESU400), combined with the xanthine oxidase inhibitor (XOI) allopurinol (ALLO; CLEAR 1 and 2) or febuxostat (FBX; CRYSTAL), achieved serum uric acid (sUA) targets at 6 months versus xanthine oxidase inhibitor (XOI) + placebo (PBO). Objectives To evaluate the impact of long-term treatment with lesinurad + XOI on tophus and flares for at least 1 year and up to 2 years. Methods Patients completing 12 months in the core CLEAR and CRYSTAL studies could enroll in respective uncontrolled, open-label extension studies (NCT01808131; NCT01808144). Patients randomized to LESU200 + XOI or LESU400 + XOI in the core studies who continued on combination therapy in the extension studies were analyzed. Efficacy endpoints included: (1) proportions of patients with complete resolution (CR) of ≥1 target tophus (i.e. measurable tophus on hands/wrists and/or feet/ankles 5–20 mm in longest diameter), (2) percent reductions in the total area of all target tophi, and (3) proportions of patients experiencing gout flares requiring treatment (GFRT). Results A total of 239 (LESU200+ALLO) and 232 (LESU400+ALLO) patients continued in the CLEAR extension; 64 (LESU200+FBX) and 65 (LESU400+FBX) patients continued in the CRYSTAL extension. Proportions of patients with CR of ≥1 target tophus increased from end of core study (1 year) to 2 years: from 25.0% to 43.8% in LESU200+ALLO and 30.3% to 36.4% in LESU400+ALLO, and from 26.6% to 53.1% in LESU200+FBX and 35.4% to 58.5% in LESU400+FBX (LOCF). Percent reduction in the total area of all target tophi versus baseline changed from end of core study to 2 years: from 11.6% to 41.8% in LESU200+ALLO and 42.7% to 49.3% in LESU400+ALLO, and from 54.8% to 68.3% in LESU200+FBX and 58.6% to 72.4% in LESU400+FBX (LOCF). Proportions of subjects with a GFRT per month decreased during continued combination treatment in both extension studies (Figure). The proportions of patients with a GFRT during Months 1, 12, and 24 were, respectively, 16.3, 7.9, and 5.6 in LESU200+ALLO; 18.1, 6.9, and 3.0 in LESU400+ALLO; 26.6, 10.9, 6.3 in LESU200+FBX; and 36.9, 4.6, 1.9 in LESU400+FBX. Extended treatment with LESU + XOI did not result in increased exposure-adjusted incidence rates of adverse events (AEs), AEs leading to discontinuation of lesinurad, serious AEs, or clinical laboratory abnormalities. Conclusions The CLEAR and CRYSTAL extension studies showed that patients treated with lesinurad + XOI for up to 2 years exhibited continued increases in the rate of complete resolution of tophi and reduction in tophus area, as well as decreased rates of GFRT. Acknowledgement This study was funded by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca. Disclosure of Interest T. Bardin Grant/research support from: Ipsen, Menarini., Consultant for: AstraZeneca, Ipsen, Menarini, Novartis, Savient, Sobi, Takeda, Cymabay., N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis., Consultant for: AstraZeneca, Fonterra, Pfizer, Takeda, Crealta, Cymabay., Speakers bureau: AstraZeneca, Teijin., R. Terkeltaub Consultant for: Ardea Biosciences, AstraZeneca, Takeda, Relburn, REVIVE., C. Storgard Employee of: Ardea Biosciences, a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, a member of the AstraZeneca Group., J. Hu Employee of: Ardea Biosciences, a member of the AstraZeneca Group., F. Perez-Ruiz Consultant for: AstraZeneca, Menarini, Pfizer., Speakers bureau: AstraZeneca, Menarini, Pfizer.

  • SAT0307 Lesinurad Monotherapy in Gout Patients Intolerant to Xanthine Oxidase Inhibitors (Light): A Randomized, Double-Blind, Placebo-Controlled, 6-Month Phase III Clinical Trial
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Anne-kathrin Tausche, Rieke Alten, Nicola Dalbeth, J. Kopicko, N. Bhakta, C. Storgard, Scott Baumgartner, K. Saag
    Abstract:

    Background Lesinurad (LESU; RDEA594) is a selective uric acid reabsorption inhibitor (SURI) being investigated for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI). Objectives LIGHT is a multinational randomized, double-blind, placebo-controlled, 6-month phase III clinical trial to determine the efficacy and safety of LESU 400mg monotherapy in patients intolerant to an XOI (NCT01508702). Methods Gout patients with intolerance/contraindication to XOI and serum uric acid (sUA) ≥6.5 mg/dL were randomized to LESU (400mg oral, once daily) or placebo (PBO). The primary endpoint was the proportion of patients with sUA Results Patients (LESU, 107; PBO, 107) were primarily white (81.8%) and male (91.1%) with mean ± SD age of 54.4±12.3 years, 11.2±8.7 years since gout diagnosis, 6.2±7.3 gout flares in past 12 months, tophi (25% of patients), renal impairment (58.9% with estimated creatinine clearance [eCrCL] Conclusions In this multinational study of gout patients with high sUA and intolerance/contraindication to an XOI, nearly one third of patients treated with LESU 400 mg achieved sUA Acknowledgements Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. Disclosure of Interest A.-K. Tausche Consultant for: Menarini, Ipsen, Novartis, Savient, AstraZeneca, Speakers bureau: Menarini, Ipsen, Novartis, Savient, AstraZeneca, R. Alten Grant/research support from: AstraZeneca, N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Consultant for: AstraZeneca, Fonterra, Takeda, Metabolex, Speakers bureau: Savient, Menarini, Novartis, Takeda, J. Kopicko Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, N. Bhakta Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, C. Storgard Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, S. Baumgartner Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, K. Saag Grant/research support from: Ardea/AstraZeneca, Crealta, Takeda, Consultant for: Amgen, Ardea/AstraZeneca, CORONA, Crealta

  • SAT0329 Lesinurad, A Novel Selective Uric Acid Reabsorption Inhibitor, in Combination with Febuxostat, in Patients with Tophaceous Gout: the Crystal Phase III Clinical Trial
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Nicola Dalbeth, J. Kopicko, N. Bhakta, C. Storgard, Scott Baumgartner, Graeme Jones, Robert Terkeltaub, Dinesh Khanna, Maple Fung, Fernando Perez-ruiz
    Abstract:

    Background Lesinurad (LESU; RDEA594) is a selective uric acid reabsorption inhibitor (SURI) being investigated for the treatment of gout in combination with a xanthine oxidase inhibitor. Objectives The CRYSTAL study is a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial of LESU in combination with febuxostat (FBX) to determine efficacy and safety of combination therapy compared with FBX monotherapy in patients with tophaceous gout (NCT01510769). Methods Patients with gout, ages 18-85 yrs, with serum uric acid (sUA) ≥8 mg/dL (≥6 mg/dL on urate lowering therapy) and ≥1 tophus were given FBX 80 mg qd for 3 weeks before randomization to LESU (200 mg or 400 mg oral, qd) in combination with FBX or placebo (PBO) + FBX. Primary endpoint was proportion of patients with sUA Results Patients (N=324) were white (79.9%) and male (95.4%) with mean ± SD age of 54.1±11.0 yrs and 14.7±10.9 yrs since gout diagnosis. sUA was 8.7±1.6 mg/dL at screening and 5.3±1.6 mg/dL on FBX at randomization (28% with sUA ≥6 mg/dL). More patients achieved sUA levels Conclusions In patients with tophaceous gout, LESU (200 or 400 mg) in combination with FBX increased the proportion of patients achieving sUA Acknowledgements Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. Disclosure of Interest N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Speakers bureau: Savient, Menarini, Novartis, Takeda, and Advisory Boards for AstraZeneca, Fonterra, Takeda, Metabolex, G. Jones Grant/research support from: Abbvie, Ardea, Novartis, Auxilium, Consultant for: Pfizer, Roche, Hospira and Janssen, Speakers bureau: UCB, Roche, Janssen, Abbvie, Novartis, Mundipharma, Amgen, BMS, Pfizer, R. Terkeltaub Consultant for: AstraZeneca, Takeda, Revive, Relburn, UCB, D. Khanna Grant/research support from: AstraZeneca, Consultant for: AstraZeneca, Takeda, J. Kopicko Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, N. Bhakta Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, M. Fung Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, C. Storgard Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, S. Baumgartner Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, F. Perez-Ruiz Grant/research support from: Spanish Health Ministry, Spanish Rheumatology Foundation, and Cruces Hospital Rheumatologists Association, Consultant for: AstraZeneca, Menarini, Metabolex, Novartis, Pfizer, and SOBI, Speakers bureau: AstraZeneca and Menarini

Nicole J. Gaudette - One of the best experts on this subject based on the ideXlab platform.

  • The effect of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of turkey sausages
    Journal of the Science of Food and Agriculture, 2015
    Co-Authors: Zeb Pietrasik, Nicole J. Gaudette
    Abstract:

    Two salt replacers (Ocean's Flavor - OF45, OF60) and one flavor enhancer [Fonterra™ 'Savoury Powder' (SP)] were evaluated for their ability to effectively reduce sodium, while maintaining the functional and sensory properties of restructured hams. Product functionality and safety were assessed using instrumental measures (yield, purge, pH, expressible moisture, proximate composition, sodium content, color, texture) and microbiological assessment. Sensory attributes were evaluated using consumer sensory panelists.All alternative formulations resulted in products with sodium contents below the Health CheckTMProgram guidelines, without detrimental effect on water binding and texture in treatments when NaCl was substituted with sea salt replacers (OF45, OF60). Sodium reduction had no effect on the shelf life of the cooked ham with up to 60days of refrigerated storage. Consumer hedonics for flavor and aftertaste were lower for OF45 and OF60 compared to control, suggesting that these salt replacers may not be appropriate for inclusion in these products. © 2013 Elsevier Ltd.

  • The effect of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of turkey sausages.
    Journal of the Science of Food and Agriculture, 2014
    Co-Authors: Zeb Pietrasik, Nicole J. Gaudette
    Abstract:

    BACKGROUND: Producing high-quality processed meats that contain reduced amounts of sodium chloride is a major challenge facing industry owing to the importance of sodium chloride toward the functional, microbial stability and sensory properties of these products. In order to create reduced sodium alternatives, a number of commercial salt replacers and flavor enhancers have entered the market; however, their ability to be applied in processed meats requires investigation. In this study, two salt replacers (Ocean’s Flavor – OF45, OF60) and one flavor enhancer (Fonterra™ Savoury Powder – SP) were evaluated for their ability to effectively reduce sodium while maintaining the functional and sensory properties of turkey sausages. Functionality via instrumental measures (yield, purge loss, pH, expressible moisture, proximate composition, sodium content, color, texture), safety (microbiological assessment) and consumer acceptability were obtained on all samples. RESULTS: All non-control treatments resulted in products with sodium chloride contents below Canada’s Health Check™ Program target for processed meats. There was no detrimental effect on water binding and texture in treatments when NaCl was substituted with OF60 sea salt replacers. Sodium reduction had no negative effect on the shelf life of the turkey sausages with up to 60 days of refrigerated storage. Consumer acceptability for all attributes did not differ significantly, except for aftertaste, which scored lowest for OF45 compared with the control (regular NaCl content). CONCLUSION: This work demonstrated that salt replacers could potentially substitute for NaCl in smoked turkey sausages; however, further flavor optimization may be required to suppress undesirable levels of bitterness elicited by some of these ingredients. © 2014 Society of Chemical Industry

  • The impact of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of restructured cooked hams.
    Meat Science, 2013
    Co-Authors: Zeb Pietrasik, Nicole J. Gaudette
    Abstract:

    Abstract Two salt replacers (Ocean's Flavor — OF45, OF60) and one flavor enhancer [Fonterra™ ‘Savoury Powder’ (SP)] were evaluated for their ability to effectively reduce sodium, while maintaining the functional and sensory properties of restructured hams. Product functionality and safety were assessed using instrumental measures (yield, purge, pH, expressible moisture, proximate composition, sodium content, color, texture) and microbiological assessment. Sensory attributes were evaluated using consumer sensory panelists. All alternative formulations resulted in products with sodium contents below the Health Check TM Program guidelines, without detrimental effect on water binding and texture in treatments when NaCl was substituted with sea salt replacers (OF45, OF60). Sodium reduction had no effect on the shelf life of the cooked ham with up to 60 days of refrigerated storage. Consumer hedonics for flavor and aftertaste were lower for OF45 and OF60 compared to control, suggesting that these salt replacers may not be appropriate for inclusion in these products.

Fernando Perez-ruiz - One of the best experts on this subject based on the ideXlab platform.

  • AB1058 Time to resolution of tophi with urate lowering agents: A literature analysis of randomized trials
    Annals of the Rheumatic Diseases, 2020
    Co-Authors: Michael Becker, Fernando Perez-ruiz, R. Yood, Nicola Dalbeth
    Abstract:

    Background The tophus is a pathognomonic feature of chronic gout and may cause disability and joint damage. Accordingly, OMERACT has endorsed tophus measurement as a key domain in clinical trials of chronic gout. The approval of febuxostat (FEB) in 2009 and pegloticase (PGL) in 2010 has been accompanied by publications describing clinical trials of urate-lowering therapies (ULTs). These trials also provide detailed data, not previously available, on change in tophus burden in response to treatment in defined gout populations. Objectives We compared tophus resolution in published clinical trials of ULTs that included such measurements. Methods A PubMed search using the terms “gout” and “tophi OR tophus” was performed with the following limits applied: clinical trial, humans, and English. The 15 articles retrieved were evaluated for appropriateness and used to identify additional publications/abstracts. Six trials met the analysis criteria. Results Conclusions Clinical trials of ULTs have not used consistent methods or timepoints to evaluate tophus response. Nevertheless, pegloticase treatment results in more robust and rapid resolution of tophi compared to treatment with febuxostat or allopurinol. References Wallace et al. Arth Rheum 1977;20:895-900. Disclosure of Interest M. Becker Grant/Research support from: Savient, Takeda, Consultant for: Savient, Takeda, Ardea, BioCryst, Regeneron, URL/Mutual/Metabolex/Chugai, R. Yood Grant/Research support from: Savient, Takeda, F. Perez-Ruiz Consultant for: Ardea, Menarini, Novartis, Savient, Speakers Bureau: Ardea, Menarini, Novartis, Savient, N. Dalbeth Grant/Research support from: Fonterra, Consultant for: Takeda, Ardea, Novartis, Abbott, Roche

  • THU0537 Clinical Response of Tophus and Flares To Extended Use of Lesinurad in Combination with A Xanthine Oxidase Inhibitor in Patients with Gout
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Thomas Bardin, Nicola Dalbeth, C. Storgard, Robert Terkeltaub, Maple Fung, J Hu, Fernando Perez-ruiz
    Abstract:

    Background Three randomized, double-blind, Phase III trials reported that greater proportions of patients treated with lesinurad 200 mg (LESU200) or 400 mg (LESU400), combined with the xanthine oxidase inhibitor (XOI) allopurinol (ALLO; CLEAR 1 and 2) or febuxostat (FBX; CRYSTAL), achieved serum uric acid (sUA) targets at 6 months versus xanthine oxidase inhibitor (XOI) + placebo (PBO). Objectives To evaluate the impact of long-term treatment with lesinurad + XOI on tophus and flares for at least 1 year and up to 2 years. Methods Patients completing 12 months in the core CLEAR and CRYSTAL studies could enroll in respective uncontrolled, open-label extension studies (NCT01808131; NCT01808144). Patients randomized to LESU200 + XOI or LESU400 + XOI in the core studies who continued on combination therapy in the extension studies were analyzed. Efficacy endpoints included: (1) proportions of patients with complete resolution (CR) of ≥1 target tophus (i.e. measurable tophus on hands/wrists and/or feet/ankles 5–20 mm in longest diameter), (2) percent reductions in the total area of all target tophi, and (3) proportions of patients experiencing gout flares requiring treatment (GFRT). Results A total of 239 (LESU200+ALLO) and 232 (LESU400+ALLO) patients continued in the CLEAR extension; 64 (LESU200+FBX) and 65 (LESU400+FBX) patients continued in the CRYSTAL extension. Proportions of patients with CR of ≥1 target tophus increased from end of core study (1 year) to 2 years: from 25.0% to 43.8% in LESU200+ALLO and 30.3% to 36.4% in LESU400+ALLO, and from 26.6% to 53.1% in LESU200+FBX and 35.4% to 58.5% in LESU400+FBX (LOCF). Percent reduction in the total area of all target tophi versus baseline changed from end of core study to 2 years: from 11.6% to 41.8% in LESU200+ALLO and 42.7% to 49.3% in LESU400+ALLO, and from 54.8% to 68.3% in LESU200+FBX and 58.6% to 72.4% in LESU400+FBX (LOCF). Proportions of subjects with a GFRT per month decreased during continued combination treatment in both extension studies (Figure). The proportions of patients with a GFRT during Months 1, 12, and 24 were, respectively, 16.3, 7.9, and 5.6 in LESU200+ALLO; 18.1, 6.9, and 3.0 in LESU400+ALLO; 26.6, 10.9, 6.3 in LESU200+FBX; and 36.9, 4.6, 1.9 in LESU400+FBX. Extended treatment with LESU + XOI did not result in increased exposure-adjusted incidence rates of adverse events (AEs), AEs leading to discontinuation of lesinurad, serious AEs, or clinical laboratory abnormalities. Conclusions The CLEAR and CRYSTAL extension studies showed that patients treated with lesinurad + XOI for up to 2 years exhibited continued increases in the rate of complete resolution of tophi and reduction in tophus area, as well as decreased rates of GFRT. Acknowledgement This study was funded by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca. Disclosure of Interest T. Bardin Grant/research support from: Ipsen, Menarini., Consultant for: AstraZeneca, Ipsen, Menarini, Novartis, Savient, Sobi, Takeda, Cymabay., N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis., Consultant for: AstraZeneca, Fonterra, Pfizer, Takeda, Crealta, Cymabay., Speakers bureau: AstraZeneca, Teijin., R. Terkeltaub Consultant for: Ardea Biosciences, AstraZeneca, Takeda, Relburn, REVIVE., C. Storgard Employee of: Ardea Biosciences, a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, a member of the AstraZeneca Group., J. Hu Employee of: Ardea Biosciences, a member of the AstraZeneca Group., F. Perez-Ruiz Consultant for: AstraZeneca, Menarini, Pfizer., Speakers bureau: AstraZeneca, Menarini, Pfizer.

  • SAT0329 Lesinurad, A Novel Selective Uric Acid Reabsorption Inhibitor, in Combination with Febuxostat, in Patients with Tophaceous Gout: the Crystal Phase III Clinical Trial
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Nicola Dalbeth, J. Kopicko, N. Bhakta, C. Storgard, Scott Baumgartner, Graeme Jones, Robert Terkeltaub, Dinesh Khanna, Maple Fung, Fernando Perez-ruiz
    Abstract:

    Background Lesinurad (LESU; RDEA594) is a selective uric acid reabsorption inhibitor (SURI) being investigated for the treatment of gout in combination with a xanthine oxidase inhibitor. Objectives The CRYSTAL study is a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial of LESU in combination with febuxostat (FBX) to determine efficacy and safety of combination therapy compared with FBX monotherapy in patients with tophaceous gout (NCT01510769). Methods Patients with gout, ages 18-85 yrs, with serum uric acid (sUA) ≥8 mg/dL (≥6 mg/dL on urate lowering therapy) and ≥1 tophus were given FBX 80 mg qd for 3 weeks before randomization to LESU (200 mg or 400 mg oral, qd) in combination with FBX or placebo (PBO) + FBX. Primary endpoint was proportion of patients with sUA Results Patients (N=324) were white (79.9%) and male (95.4%) with mean ± SD age of 54.1±11.0 yrs and 14.7±10.9 yrs since gout diagnosis. sUA was 8.7±1.6 mg/dL at screening and 5.3±1.6 mg/dL on FBX at randomization (28% with sUA ≥6 mg/dL). More patients achieved sUA levels Conclusions In patients with tophaceous gout, LESU (200 or 400 mg) in combination with FBX increased the proportion of patients achieving sUA Acknowledgements Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. Disclosure of Interest N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Speakers bureau: Savient, Menarini, Novartis, Takeda, and Advisory Boards for AstraZeneca, Fonterra, Takeda, Metabolex, G. Jones Grant/research support from: Abbvie, Ardea, Novartis, Auxilium, Consultant for: Pfizer, Roche, Hospira and Janssen, Speakers bureau: UCB, Roche, Janssen, Abbvie, Novartis, Mundipharma, Amgen, BMS, Pfizer, R. Terkeltaub Consultant for: AstraZeneca, Takeda, Revive, Relburn, UCB, D. Khanna Grant/research support from: AstraZeneca, Consultant for: AstraZeneca, Takeda, J. Kopicko Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, N. Bhakta Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, M. Fung Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, C. Storgard Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, S. Baumgartner Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, F. Perez-Ruiz Grant/research support from: Spanish Health Ministry, Spanish Rheumatology Foundation, and Cruces Hospital Rheumatologists Association, Consultant for: AstraZeneca, Menarini, Metabolex, Novartis, Pfizer, and SOBI, Speakers bureau: AstraZeneca and Menarini

  • SAT0313 Relationship Between Sustained Lowering of Serum Urate Levels and Improvements in Gout Flares and Tophus Area: Pooled Exploratory Analysis of Gout Subjects Receiving Lesinurad and Xanthine Oxidase Inhibitor Combination Therapy
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Robert Terkeltaub, J. Kopicko, C. Storgard, Maple Fung, Fernando Perez-ruiz, Nicola Dalbeth
    Abstract:

    Background Previous studies have shown that long-term urate-lowering therapy is required for improvements in gout flare frequency and tophi reduction, and that lower serum uric acid (sUA) levels may result in greater benefit. However, optimal sUA levels to jointly achieve these outcomes within a year using single or combination oral therapies are uncertain. Objectives To assess the impact of sustained sUA lowering to determine if the magnitude of continual low sUA levels results in greater tophus size reduction and fewer patients experiencing gout flares requiring treatment (GFRT). Methods Patients, irrespective of treatment assignment, were combined from 3 Phase III clinical studies examining the efficacy of lesinurad, a selective uric acid reabsorption inhibitor (SURI), in combination with a xanthine oxidase inhibitor (allopurinol: CLEAR 1 [NCT01510158], CLEAR 2 [NCT01493531]), or febuxostat: CRYSTAL [NCT01510769]). For this analysis, GFRTs were assessed during the last quarter of study treatment (end of Month 9 to end of Month 12) and reduction in target tophus area (measured using Vernier calipers) was assessed over the duration of the study. Patients were categorized by on-study median sUA levels of ≥6, 5– Results In total, 1537 patients were eligible for analysis; 95% were male, 78% were white, and mean (SD) age was 42 (11) years. A total of 474 patients (30.8%) had ≥1 target tophi that were followed in the studies. A positive relationship between lower sUA and greater tophus area reduction and GFRT was observed. In patients with ≥1 target tophi at baseline in the 3 studies, those with lowest on-study median sUA levels achieved greatest reduction in tophus area (Fig. 1A). Patients with median sUA Similarly, those with lower sUA levels were less likely to have GFRT. During the last quarter of the study, 12.2% with median sUA Conclusions These findings demonstrate that degree of clinical benefit (reduction in GFRT or tophus area) within 12 months correlates with the magnitude of sustained sUA lowering using oral sUA-lowering therapy. The results provide additional confirmation of the validity of sUA lowering as a surrogate for clinically meaningful effects in gout patients and point to potential benchmarks. In this context, patients with median sUA Acknowledgements This study was funded by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca. Disclosure of Interest R. Terkeltaub Consultant for: Ardea Biosciences, AstraZeneca, Takeda, Relburn, REVIVE, F. Perez-Ruiz Consultant for: Menarini, AstraZeneca, Pfizer, Speakers bureau: Menarini, AstraZeneca, Pfizer, C. Storgard Shareholder of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., J. Kopicko Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Speakers bureau: Savient, Menarini, Novartis, Teijin, and Advisory Boards for AstraZeneca, Fonterra, Takeda, Pfizer, Metabolex

Zeb Pietrasik - One of the best experts on this subject based on the ideXlab platform.

  • The effect of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of turkey sausages
    Journal of the Science of Food and Agriculture, 2015
    Co-Authors: Zeb Pietrasik, Nicole J. Gaudette
    Abstract:

    Two salt replacers (Ocean's Flavor - OF45, OF60) and one flavor enhancer [Fonterra™ 'Savoury Powder' (SP)] were evaluated for their ability to effectively reduce sodium, while maintaining the functional and sensory properties of restructured hams. Product functionality and safety were assessed using instrumental measures (yield, purge, pH, expressible moisture, proximate composition, sodium content, color, texture) and microbiological assessment. Sensory attributes were evaluated using consumer sensory panelists.All alternative formulations resulted in products with sodium contents below the Health CheckTMProgram guidelines, without detrimental effect on water binding and texture in treatments when NaCl was substituted with sea salt replacers (OF45, OF60). Sodium reduction had no effect on the shelf life of the cooked ham with up to 60days of refrigerated storage. Consumer hedonics for flavor and aftertaste were lower for OF45 and OF60 compared to control, suggesting that these salt replacers may not be appropriate for inclusion in these products. © 2013 Elsevier Ltd.

  • The effect of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of turkey sausages.
    Journal of the Science of Food and Agriculture, 2014
    Co-Authors: Zeb Pietrasik, Nicole J. Gaudette
    Abstract:

    BACKGROUND: Producing high-quality processed meats that contain reduced amounts of sodium chloride is a major challenge facing industry owing to the importance of sodium chloride toward the functional, microbial stability and sensory properties of these products. In order to create reduced sodium alternatives, a number of commercial salt replacers and flavor enhancers have entered the market; however, their ability to be applied in processed meats requires investigation. In this study, two salt replacers (Ocean’s Flavor – OF45, OF60) and one flavor enhancer (Fonterra™ Savoury Powder – SP) were evaluated for their ability to effectively reduce sodium while maintaining the functional and sensory properties of turkey sausages. Functionality via instrumental measures (yield, purge loss, pH, expressible moisture, proximate composition, sodium content, color, texture), safety (microbiological assessment) and consumer acceptability were obtained on all samples. RESULTS: All non-control treatments resulted in products with sodium chloride contents below Canada’s Health Check™ Program target for processed meats. There was no detrimental effect on water binding and texture in treatments when NaCl was substituted with OF60 sea salt replacers. Sodium reduction had no negative effect on the shelf life of the turkey sausages with up to 60 days of refrigerated storage. Consumer acceptability for all attributes did not differ significantly, except for aftertaste, which scored lowest for OF45 compared with the control (regular NaCl content). CONCLUSION: This work demonstrated that salt replacers could potentially substitute for NaCl in smoked turkey sausages; however, further flavor optimization may be required to suppress undesirable levels of bitterness elicited by some of these ingredients. © 2014 Society of Chemical Industry

  • The impact of salt replacers and flavor enhancer on the processing characteristics and consumer acceptance of restructured cooked hams.
    Meat Science, 2013
    Co-Authors: Zeb Pietrasik, Nicole J. Gaudette
    Abstract:

    Abstract Two salt replacers (Ocean's Flavor — OF45, OF60) and one flavor enhancer [Fonterra™ ‘Savoury Powder’ (SP)] were evaluated for their ability to effectively reduce sodium, while maintaining the functional and sensory properties of restructured hams. Product functionality and safety were assessed using instrumental measures (yield, purge, pH, expressible moisture, proximate composition, sodium content, color, texture) and microbiological assessment. Sensory attributes were evaluated using consumer sensory panelists. All alternative formulations resulted in products with sodium contents below the Health Check TM Program guidelines, without detrimental effect on water binding and texture in treatments when NaCl was substituted with sea salt replacers (OF45, OF60). Sodium reduction had no effect on the shelf life of the cooked ham with up to 60 days of refrigerated storage. Consumer hedonics for flavor and aftertaste were lower for OF45 and OF60 compared to control, suggesting that these salt replacers may not be appropriate for inclusion in these products.

Robert Terkeltaub - One of the best experts on this subject based on the ideXlab platform.

  • Review: Gout: A Roadmap to Approaches for Improving Global Outcomes.
    Arthritis & Rheumatism, 2016
    Co-Authors: Nicola Dalbeth, Hyon K. Choi, Robert Terkeltaub
    Abstract:

    Gout: A roadmap to approaches for improving global outcomes Nicola Dalbeth 1 *, Hyon K. Choi 2 *, Robert Terkeltaub 3 *contributed equally to this manuscript Nicola Dalbeth MB ChB, MD, Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz Hyon K. Choi, MD, PhD, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA hchoi@mgh.harvard.edu Robert Terkeltaub, MD, VA San Diego Healthcare System, San Diego, CA, Dept. of Medicine, University of California San Diego, San Diego, CA rterkeltaub@ucsd.edu Supported by the Health Research Council of New Zealand (9101-3708025)(ND), NIH (R01AR065944)(HKC), and VA Research Service (RT). Dr. Dalbeth has received grant support from AstraZeneca and has participated on speaker bureaus for Menarini, ARDEA/Astra-Zeneca, Takeda, and as a consultant for Astra-Zeneca, Fonterra, Takeda, Pfizer, CymaBay, and Crealta. Dr. Choi has served as consultant for Takeda and ARDEA/Astra-Zeneca. Dr. Terkeltaub has served as a consultant for ARDEA/Astra-Zeneca, SOBI, Revive, Selecta, Aequus, ProteoThera, Horizon, Relburn, and CymaBay. Correspondence to: Robert Terkeltaub MD, VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, CA 92161. Telephone: 858 642 3519. Fax: 858 552 7425, email: rterkeltaub@ucsd.edu Running Head: Roadmap to improved gout outcomes Keywords: Hyperuricemia, ABCG2, URAT1, NLRP3 inflammasome, Precision Medicine

  • THU0537 Clinical Response of Tophus and Flares To Extended Use of Lesinurad in Combination with A Xanthine Oxidase Inhibitor in Patients with Gout
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Thomas Bardin, Nicola Dalbeth, C. Storgard, Robert Terkeltaub, Maple Fung, J Hu, Fernando Perez-ruiz
    Abstract:

    Background Three randomized, double-blind, Phase III trials reported that greater proportions of patients treated with lesinurad 200 mg (LESU200) or 400 mg (LESU400), combined with the xanthine oxidase inhibitor (XOI) allopurinol (ALLO; CLEAR 1 and 2) or febuxostat (FBX; CRYSTAL), achieved serum uric acid (sUA) targets at 6 months versus xanthine oxidase inhibitor (XOI) + placebo (PBO). Objectives To evaluate the impact of long-term treatment with lesinurad + XOI on tophus and flares for at least 1 year and up to 2 years. Methods Patients completing 12 months in the core CLEAR and CRYSTAL studies could enroll in respective uncontrolled, open-label extension studies (NCT01808131; NCT01808144). Patients randomized to LESU200 + XOI or LESU400 + XOI in the core studies who continued on combination therapy in the extension studies were analyzed. Efficacy endpoints included: (1) proportions of patients with complete resolution (CR) of ≥1 target tophus (i.e. measurable tophus on hands/wrists and/or feet/ankles 5–20 mm in longest diameter), (2) percent reductions in the total area of all target tophi, and (3) proportions of patients experiencing gout flares requiring treatment (GFRT). Results A total of 239 (LESU200+ALLO) and 232 (LESU400+ALLO) patients continued in the CLEAR extension; 64 (LESU200+FBX) and 65 (LESU400+FBX) patients continued in the CRYSTAL extension. Proportions of patients with CR of ≥1 target tophus increased from end of core study (1 year) to 2 years: from 25.0% to 43.8% in LESU200+ALLO and 30.3% to 36.4% in LESU400+ALLO, and from 26.6% to 53.1% in LESU200+FBX and 35.4% to 58.5% in LESU400+FBX (LOCF). Percent reduction in the total area of all target tophi versus baseline changed from end of core study to 2 years: from 11.6% to 41.8% in LESU200+ALLO and 42.7% to 49.3% in LESU400+ALLO, and from 54.8% to 68.3% in LESU200+FBX and 58.6% to 72.4% in LESU400+FBX (LOCF). Proportions of subjects with a GFRT per month decreased during continued combination treatment in both extension studies (Figure). The proportions of patients with a GFRT during Months 1, 12, and 24 were, respectively, 16.3, 7.9, and 5.6 in LESU200+ALLO; 18.1, 6.9, and 3.0 in LESU400+ALLO; 26.6, 10.9, 6.3 in LESU200+FBX; and 36.9, 4.6, 1.9 in LESU400+FBX. Extended treatment with LESU + XOI did not result in increased exposure-adjusted incidence rates of adverse events (AEs), AEs leading to discontinuation of lesinurad, serious AEs, or clinical laboratory abnormalities. Conclusions The CLEAR and CRYSTAL extension studies showed that patients treated with lesinurad + XOI for up to 2 years exhibited continued increases in the rate of complete resolution of tophi and reduction in tophus area, as well as decreased rates of GFRT. Acknowledgement This study was funded by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca. Disclosure of Interest T. Bardin Grant/research support from: Ipsen, Menarini., Consultant for: AstraZeneca, Ipsen, Menarini, Novartis, Savient, Sobi, Takeda, Cymabay., N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis., Consultant for: AstraZeneca, Fonterra, Pfizer, Takeda, Crealta, Cymabay., Speakers bureau: AstraZeneca, Teijin., R. Terkeltaub Consultant for: Ardea Biosciences, AstraZeneca, Takeda, Relburn, REVIVE., C. Storgard Employee of: Ardea Biosciences, a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, a member of the AstraZeneca Group., J. Hu Employee of: Ardea Biosciences, a member of the AstraZeneca Group., F. Perez-Ruiz Consultant for: AstraZeneca, Menarini, Pfizer., Speakers bureau: AstraZeneca, Menarini, Pfizer.

  • SAT0329 Lesinurad, A Novel Selective Uric Acid Reabsorption Inhibitor, in Combination with Febuxostat, in Patients with Tophaceous Gout: the Crystal Phase III Clinical Trial
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Nicola Dalbeth, J. Kopicko, N. Bhakta, C. Storgard, Scott Baumgartner, Graeme Jones, Robert Terkeltaub, Dinesh Khanna, Maple Fung, Fernando Perez-ruiz
    Abstract:

    Background Lesinurad (LESU; RDEA594) is a selective uric acid reabsorption inhibitor (SURI) being investigated for the treatment of gout in combination with a xanthine oxidase inhibitor. Objectives The CRYSTAL study is a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial of LESU in combination with febuxostat (FBX) to determine efficacy and safety of combination therapy compared with FBX monotherapy in patients with tophaceous gout (NCT01510769). Methods Patients with gout, ages 18-85 yrs, with serum uric acid (sUA) ≥8 mg/dL (≥6 mg/dL on urate lowering therapy) and ≥1 tophus were given FBX 80 mg qd for 3 weeks before randomization to LESU (200 mg or 400 mg oral, qd) in combination with FBX or placebo (PBO) + FBX. Primary endpoint was proportion of patients with sUA Results Patients (N=324) were white (79.9%) and male (95.4%) with mean ± SD age of 54.1±11.0 yrs and 14.7±10.9 yrs since gout diagnosis. sUA was 8.7±1.6 mg/dL at screening and 5.3±1.6 mg/dL on FBX at randomization (28% with sUA ≥6 mg/dL). More patients achieved sUA levels Conclusions In patients with tophaceous gout, LESU (200 or 400 mg) in combination with FBX increased the proportion of patients achieving sUA Acknowledgements Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. Disclosure of Interest N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Speakers bureau: Savient, Menarini, Novartis, Takeda, and Advisory Boards for AstraZeneca, Fonterra, Takeda, Metabolex, G. Jones Grant/research support from: Abbvie, Ardea, Novartis, Auxilium, Consultant for: Pfizer, Roche, Hospira and Janssen, Speakers bureau: UCB, Roche, Janssen, Abbvie, Novartis, Mundipharma, Amgen, BMS, Pfizer, R. Terkeltaub Consultant for: AstraZeneca, Takeda, Revive, Relburn, UCB, D. Khanna Grant/research support from: AstraZeneca, Consultant for: AstraZeneca, Takeda, J. Kopicko Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, N. Bhakta Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, M. Fung Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, C. Storgard Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, S. Baumgartner Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca group, F. Perez-Ruiz Grant/research support from: Spanish Health Ministry, Spanish Rheumatology Foundation, and Cruces Hospital Rheumatologists Association, Consultant for: AstraZeneca, Menarini, Metabolex, Novartis, Pfizer, and SOBI, Speakers bureau: AstraZeneca and Menarini

  • SAT0313 Relationship Between Sustained Lowering of Serum Urate Levels and Improvements in Gout Flares and Tophus Area: Pooled Exploratory Analysis of Gout Subjects Receiving Lesinurad and Xanthine Oxidase Inhibitor Combination Therapy
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Robert Terkeltaub, J. Kopicko, C. Storgard, Maple Fung, Fernando Perez-ruiz, Nicola Dalbeth
    Abstract:

    Background Previous studies have shown that long-term urate-lowering therapy is required for improvements in gout flare frequency and tophi reduction, and that lower serum uric acid (sUA) levels may result in greater benefit. However, optimal sUA levels to jointly achieve these outcomes within a year using single or combination oral therapies are uncertain. Objectives To assess the impact of sustained sUA lowering to determine if the magnitude of continual low sUA levels results in greater tophus size reduction and fewer patients experiencing gout flares requiring treatment (GFRT). Methods Patients, irrespective of treatment assignment, were combined from 3 Phase III clinical studies examining the efficacy of lesinurad, a selective uric acid reabsorption inhibitor (SURI), in combination with a xanthine oxidase inhibitor (allopurinol: CLEAR 1 [NCT01510158], CLEAR 2 [NCT01493531]), or febuxostat: CRYSTAL [NCT01510769]). For this analysis, GFRTs were assessed during the last quarter of study treatment (end of Month 9 to end of Month 12) and reduction in target tophus area (measured using Vernier calipers) was assessed over the duration of the study. Patients were categorized by on-study median sUA levels of ≥6, 5– Results In total, 1537 patients were eligible for analysis; 95% were male, 78% were white, and mean (SD) age was 42 (11) years. A total of 474 patients (30.8%) had ≥1 target tophi that were followed in the studies. A positive relationship between lower sUA and greater tophus area reduction and GFRT was observed. In patients with ≥1 target tophi at baseline in the 3 studies, those with lowest on-study median sUA levels achieved greatest reduction in tophus area (Fig. 1A). Patients with median sUA Similarly, those with lower sUA levels were less likely to have GFRT. During the last quarter of the study, 12.2% with median sUA Conclusions These findings demonstrate that degree of clinical benefit (reduction in GFRT or tophus area) within 12 months correlates with the magnitude of sustained sUA lowering using oral sUA-lowering therapy. The results provide additional confirmation of the validity of sUA lowering as a surrogate for clinically meaningful effects in gout patients and point to potential benchmarks. In this context, patients with median sUA Acknowledgements This study was funded by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and was funded by AstraZeneca. Disclosure of Interest R. Terkeltaub Consultant for: Ardea Biosciences, AstraZeneca, Takeda, Relburn, REVIVE, F. Perez-Ruiz Consultant for: Menarini, AstraZeneca, Pfizer, Speakers bureau: Menarini, AstraZeneca, Pfizer, C. Storgard Shareholder of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., J. Kopicko Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Speakers bureau: Savient, Menarini, Novartis, Teijin, and Advisory Boards for AstraZeneca, Fonterra, Takeda, Pfizer, Metabolex