Expert Opinion on Pegloticase with Concomitant Immunomodulatory Therapy in the Treatment of Uncontrolled Gout to Improve Efficacy, Safety, and Durability of Response

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Abstract

Purpose of Review

Gout is a systemic disease from which some patients develop numerous painful tophi that adversely affect quality of life and functionality. Some patients treated with oral urate-lowering therapy are unable to maintain serum urate levels below 6 mg/dL, and these patients, thus classified as having refractory or uncontrolled gout, often require therapy with pegloticase to reduce symptoms and tophaceous burden. The objective of this expert opinion review is to summarize the available evidence supporting the use of concomitant immunomodulators with pegloticase to prevent development of anti-drug antibodies (ADAs) when treating patients with uncontrolled gout.

Recent Findings

Emerging evidence suggests that adding an immunomodulator to pegloticase therapy can substantially increase response rates to double those observed in phase 3 randomized controlled trials.

Summary

The combination of immunomodulation with pegloticase should be considered in routine clinical practice to improve durability of response, efficacy, and safety among patients with uncontrolled gout who otherwise have limited therapeutic options.

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Most cited references 33

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Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016

Michael Chen-Xu, Chio Yokose, Sharan Rai … (2019)

To estimate the contemporary prevalences of gout and hyperuricemia and their decadal trends in the US, as well as the prevalence of urate-lowering therapy (ULT) use among gout patients, using data from the latest and prior nationally-representative samples of US men and women (National Health and Nutrition Examination Survey [NHANES] 2007–2016). Using data from 5,467 participants from NHANES 2015–2016, we estimated the latest prevalence of gout and hyperuricemia. During the NHANES, all participants were asked about a history of health professional-diagnosed gout and medication use. Hyperuricemia was defined as a serum urate level >7.0 mg/dL in men and >5.7 mg/dL in women. We examined decadal trends in these estimates using data from the NHANES 2007–2016 and ULT usage trends using the NHANES 2007–14 (the latest data available to date). The prevalence of gout was 3.9% (9.2 million) among US adults in 2015–2016 (5.2% [5.9 million] and 2.7% [3.3 million] among men and women, respectively). Mean serum urate levels were 6.0 mg/dL among men and 4.8 mg/dL among women, with hyperuricemia prevalences of 20.2% and 20.0%, respectively. The prevalences of gout and hyperuricemia remained stable over the past decade (P for trend >0.05). The prevalence of ULT use among patients with gout was 33% during 2007–2014 and remained stable over time (P for trend >0.05). In this nationally-representative sample of US adults, the prevalences of gout and hyperuricemia remain substantial albeit unchanged over the past decade. Despite this burden, only one-third of gout patients are receiving ULT.

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Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.

Janitzia Vazquez-Mellado, William Ji-Shian Huang, Anne Becker … (2011)

Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. clinicaltrials.gov Identifier: NCT00325195.

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Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

Vibeke Strand, Alejandro Balsa, Jamal Al-Saleh … (2017)

Objectives A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety. Methods Literature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn’s disease, and ulcerative colitis. Results Of >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0–83%), adalimumab (0–54%), and infliximab biosimilar CT-P13 (21–52%), and the lowest with secukinumab (0–1%), ustekinumab (1–11%), etanercept (0–13%), and golimumab (0–19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb− patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases. Conclusions Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process. Electronic supplementary material The online version of this article (doi:10.1007/s40259-017-0231-8) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

John K. Botson:

ORCID: http://orcid.org/0000-0002-9552-3351

jbotson@opaak.com

Herbert S. B. Baraf: hsbbaraf@mac.com

Robert T. Keenan: robert.keenan@duke.edu

John Albert: John.albert@rdcwi.com

Karim R. Masri: karimmasri@rheumondemand.com

Jeff Peterson: jeff.peterson@wwmedgroup.com

Christianne Yung: arthritisoffice@aol.com

Brigid Freyne: brigid.freyne@brigidfreyne.com

Mona Amin: mksmona@gmail.com

Abdul Abdellatif: Abdul71md@yahoo.com

Nehad Soloman: rheumboy@yahoo.com

N. Lawrence Edwards: edwarnl@medicine.ufl.edu

Vibeke Strand: vstrand@stanford.edu

Journal

Journal ID (nlm-ta): Curr Rheumatol Rep

Journal ID (iso-abbrev): Curr Rheumatol Rep

Title: Current Rheumatology Reports

Publisher: Springer US (New York )

ISSN (Print): 1523-3774

ISSN (Electronic): 1534-6307

Publication date (Electronic): 15 February 2022

Publication date PMC-release: 15 February 2022

Publication date (Print): 2022

Volume: 24

Issue: 1

Pages: 12-19

Affiliations

[1 ]Orthopedic Physicians Alaska 3801 Lake Otis Pkwy, Anchorage, AK 99508 USA

[2 ]GRID grid.490547.b, The Center for Rheumatology and Bone Research, ; 2730 University Blvd. West, Suite 310, Wheaton, MD 20902 USA

[3 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Duke University School of Medicine Duke Medicine Circle, ; 124 Davison Building, Durham, NC 27710 USA

[4 ]Rheumatic Disease Center, 7080 N. Port Washington Road, Glendale, WI 53217 USA

[5 ]Rheumatology OnDemand, LLC 405 Welwyn Rd, Henrico, VA 23229 USA

[6 ]The Seattle Arthritis Clinic, Kirkland, WA 98033 USA

[7 ]Private Practice, 2482 W Horizon Ridge Parkway, Suite 130, Henderson, NV 89052 USA

[8 ]Rheumatology Internal Medicine 39755, Murrieta Hot Springs Rd, Ste. F110, Murrieta, CA 92563 USA

[9 ]Arizona Arthritis and Rheumatology Associates, 11943 East Beryl Ave, Scottsdale, AZ 85259 USA

[10 ]GRID grid.39382.33, ISNI 0000 0001 2160 926X, Baylor College of Medicine, ; 600 N Kobayashi Rd., Ste 312, Webster, TX 77598 USA

[11 ]Arizona Arthritis and Rheumatology Associates, 9097 W Roberta Ln, Phoenix, AZ 85383 USA

[12 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, University of Florida, ; 1600 SW Archer Road, Room 4102, Gainesville, FL 32610 USA

[13 ]GRID grid.168010.e, ISNI 0000000419368956, Division of Immunology/Rheumatology, , Stanford University, ; 306 Ramona Road, Portola Valley, CA 94028 USA

Author information

John K. Botson http://orcid.org/0000-0002-9552-3351

Article

Publisher ID: 1055

DOI: 10.1007/s11926-022-01055-9

PMC ID: 8866281

PubMed ID: 35167037

SO-VID: c9051a57-85e9-498d-8568-0b7b842eb4bd

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date accepted : 6 December 2021

Custom metadata

ScienceOpen disciplines: Rheumatology

Keywords: antidrug antibodies,gout,immunogenicity,immunomodulation,pegloticase

Data availability:

ScienceOpen disciplines: Rheumatology

Keywords: antidrug antibodies, gout, immunogenicity, immunomodulation, pegloticase

Expert Opinion on Pegloticase with Concomitant Immunomodulatory Therapy in the Treatment of Uncontrolled Gout to Improve Efficacy, Safety, and Durability of Response

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Abstract

Purpose of Review

Recent Findings

Summary

Related collections

Efficacy of Communicating Science

Most cited references 33

Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016

Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

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