2020 American College of Rheumatology guideline for the management of gout: an interpretation_Chinese Journal of Evidence-Based Medicine

Authors：

 LI Xiu , ZHANG Jihui , NIE Yingkun

Department of Rheumatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, P.R.China;

Corresponding?author：

LI Xiu, Email: lili72710@126.com

Keywords：

Gout; Urate-lowering; Treatment; Management; Guideline interpretation

DOI：

10.7507/1672-2531.202011118

Video：

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Gout is the most common inflammatory arthritis, which is characterized by elevated urate and monosodium urate (MSU) crystal deposition in tissues, leading to arthritis, soft-tissue masses (tophi), nephrolithiasis, and urate nephropathy. It has a major impact on health-related quality of life. The American College of Rheumatology (ACR) published ACR guidelines for the management of gout in June 2020, in which 42 recommendations (including 16 strong recommendations) were generated. The guideline described indications for urate-lowering therapy (ULT), approaches to initiating, ongoing management, gout flares, and lifestyle and other medication strategies in patients with gout and in individuals with asymptomatic hyperuricemia. This paper interprets it to provide references for clinical practice.

Citation： LI Xiu, ZHANG Jihui, NIE Yingkun. 2020 American College of Rheumatology guideline for the management of gout: an interpretation. Chinese Journal of Evidence-Based Medicine, 2021, 21(4): 376-382. doi: 10.7507/1672-2531.202011118 Copy

1.	Chen-Xu M, Yokose C, Rai SK, et al. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the national health and nutrition examination survey, 2007-2016. Arthritis Rheumatol, 2019, 71(6): 991-999.
2.	朱小霞, 鄒和建, 古潔若, 等. 痛風診療規范. 中華內科雜志, 2020, 59(6): 421-426.
3.	Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken), 2012, 64(10): 1431-1446.
4.	Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken), 2012, 64(10): 1447-1461.
5.	Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis, 2017, 76(1): 29-42.
6.	FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American college of rheumatology guideline for the management of gout. Arthritis Rheumatol, 2020, 72(6): 879-895.
7.	Hultcrantz M, Rind D, Akl EA, et al. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol, 2017, 87: 4-13.
8.	Alper BS, Oettgen P, Kunnamo I, et al. Defining certainty of net benefit: a GRADE concept paper. BMJ Open, 2019, 9: e027445.
9.	Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther, 2013, 15: R137.
10.	Tausche AK, Alten R, Dalbeth N, et al. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study. Rheumatology (Oxford), 2017, 56(12): 2170-2178.
11.	Dalbeth N, Jones G, Terkeltaub R, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: findings of a phase iii clinical trial. Arthritis Rheumatol, 2017, 69(9): 1903-1913.
12.	Dalbeth N, Saag KG, Palmer WE, et al. Effects of febuxostat in early gout: a randomized, double-blind, placebo-controlled study. Arthritis Rheumatol, 2017, 69(12): 2386-2395.
13.	Kimura K, Hosoya T, Uchida S, et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial. Am J Kidney Dis, 2018, 72(6): 798-810.
14.	Stamp LK, Chapman PT, Barclay ML, et al. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. Ann Rheum Dis, 2017, 76(9): 1522-1528.
15.	Yamanaka H, Tamaki S, Ide Y, et al. Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study. Ann Rheum Dis, 2018, 77(2): 270-276.
16.	Doherty M, Jenkins W, Richardson H, et al. Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. Lancet, 2018, 392(10156): 1403-1412.
17.	Wright DF, Duffull SB, Merriman TR, et al. Predicting allopurinol response in patients with gout. Br J Clin Pharmacol, 2016, 81(2): 277-289.
18.	Stamp LK, Chapman PT, Barclay M, et al. Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study. Ann Rheum Dis, 2017, 76(12): 2065-2070.
19.	Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol, 2004, 31(12): 2429-2432.
20.	Mitha E, Schumacher HR, Fouche L, et al. Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial. Rheumatology (Oxford), 2013, 52(7): 1285-1292.
21.	Paulus HE, Schlosstein LH, Godfrey RG, et al. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum, 1974, 17(5): 609-614.
22.	Poiley J, Steinberg AS, Choi YJ, et al. A randomized, double-blind, active- and placebo-controlled efficacy and safety study of arhalofenate for reducing flare in patients with gout. Arthritis Rheumatol, 2016, 68(8): 2027-2034.
23.	Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study. Ann Rheum Dis, 2011, 70(7): 1264-1271.
24.	Schumacher HR, Evans RR, Saag KG, et al. Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. Arthritis Care Res (Hoboken), 2012, 64(10): 1462-1470.
25.	Sundy JS, Schumacher HR, Kivitz A, et al. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. J Rheumatol, 2014, 41(8): 1703-1711.
26.	Solomon DH, Liu CC, Kuo IH, et al. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis, 2016, 75(9): 1674-1679.
27.	Yu J, Qiu Q, Liang L, et al. Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting. Mod Rheumatol, 2018, 28(2): 339-344.
28.	Hill EM, Sky K, Sit M, et al. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol, 2015, 21(3): 120-125.
29.	Taylor TH, Mecchella JN, Larson RJ, et al. Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med, 2012, 125(11): 1126-1134.
30.	Feng X, Li Y, Gao W. Significance of the initiation time of urate-lowering therapy in gout patients: A retrospective research. Joint Bone Spine, 2015, 82(6): 428-431.
31.	Goldfien R, Pressman A, Jacobson A, et al. A pharmacist-staffed, virtual gout management clinic for achieving target serum uric acid levels: a randomized clinical trial. Perm J, 2016, 20(3): 15-234.
32.	Mikuls TR, Cheetham TC, Levy GD, et al. Adherence and outcomes with urate-lowering therapy: a site-randomized trial. Am J Med, 2019, 132(3): 354-361.
33.	de Lautour H, Taylor WJ, Adebajo A, et al. Development of preliminary remission criteria for gout using Delphi and 1000 minds consensus exercises. Arthritis Care Res (Hoboken), 2016, 68(5): 667-672.
34.	González-Galarza FF, Takeshita LY, Santos EJ, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res, 2015, 43(Database issue): D784-788.
35.	Jutkowitz E, Dubreuil M, Lu N, et al. The cost-effectiveness of HLA-B*5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum, 2017, 46(5): 594-600.
36.	Keller SF, Lu N, Blumenthal KG, et al. Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study. Ann Rheum Dis, 2018, 77(8): 1187-1193.
37.	White WB, Saag KG, Becker MA, et al. Cardiovascular safety of febuxostat or allopurinol in patients with Gout. N Engl J Med, 2018, 378(13): 1200-1210.
38.	Zhang M, Solomon DH, Desai RJ, et al. Assessment of cardiovascular risk in older patients with gout initiating febuxostat versus allopurinol: population-based cohort study. Circulation, 2018, 138(11): 1116-1126.
39.	Foody J, Turpin RS, Tidwell BA, et al. Major cardiovascular events in patients with gout and associated cardiovascular disease or heart failure and chronic kidney disease initiating a xanthine oxidase inhibitor. Am Health Drug Benefits, 2017, 10(8): 393-401.
40.	Saag KG, Fitz-Patrick D, Kopicko J, et al. Lesinurad combined with allopurinol: a randomized, double-blind, placebo-controlled study in gout patients with an inadequate response to standard-of-care allopurinol (a US-based study). Arthritis Rheumatol, 2017, 69(1): 203-212.
41.	Major TJ, Topless RK, Dalbeth N, et al. Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population-based cohorts. BMJ, 2018, 363: k3951.
42.	Nguyen UD, Zhang Y, Louie-Gao Q, et al. Obesity paradox in recurrent attacks of gout in observational studies: clarification and remedy. Arthritis Care Res (Hoboken), 2017, 69(4): 561-566.
43.	Waldman B, Ansquer JC, Sullivan DR, et al. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. Lancet Diabetes Endocrinol, 2018, 6(4): 310-318.
44.	FitzGerald JD, Mikuls TR, Neogi T, et al. Development of the American college of rheumatology electronic clinical quality measures for gout. Arthritis Care Res (Hoboken), 2018, 70(5): 659-671.
45.	Khan AA, Quinn TJ, Hewitt J, et al. Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta- analysis. Age (Dordr), 2016, 38: 16.
46.	Levy G, Shi JM, Cheetham TC, et al. Urate-lowering therapy in moderate to severe chronic kidney disease. Perm J, 2018, 22: 17-142.
47.	Abeles AM, Pillinger MH. Gout and cardiovascular disease: crystallized confusion. Curr Opin Rheumatol, 2019, 31(2): 118-124.

1. Chen-Xu M, Yokose C, Rai SK, et al. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the national health and nutrition examination survey, 2007-2016. Arthritis Rheumatol, 2019, 71(6): 991-999.
2. 朱小霞, 鄒和建, 古潔若, 等. 痛風診療規范. 中華內科雜志, 2020, 59(6): 421-426.
3. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken), 2012, 64(10): 1431-1446.
4. Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken), 2012, 64(10): 1447-1461.
5. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis, 2017, 76(1): 29-42.
6. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American college of rheumatology guideline for the management of gout. Arthritis Rheumatol, 2020, 72(6): 879-895.
7. Hultcrantz M, Rind D, Akl EA, et al. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol, 2017, 87: 4-13.
8. Alper BS, Oettgen P, Kunnamo I, et al. Defining certainty of net benefit: a GRADE concept paper. BMJ Open, 2019, 9: e027445.
9. Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther, 2013, 15: R137.
10. Tausche AK, Alten R, Dalbeth N, et al. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study. Rheumatology (Oxford), 2017, 56(12): 2170-2178.
11. Dalbeth N, Jones G, Terkeltaub R, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: findings of a phase iii clinical trial. Arthritis Rheumatol, 2017, 69(9): 1903-1913.
12. Dalbeth N, Saag KG, Palmer WE, et al. Effects of febuxostat in early gout: a randomized, double-blind, placebo-controlled study. Arthritis Rheumatol, 2017, 69(12): 2386-2395.
13. Kimura K, Hosoya T, Uchida S, et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial. Am J Kidney Dis, 2018, 72(6): 798-810.
14. Stamp LK, Chapman PT, Barclay ML, et al. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. Ann Rheum Dis, 2017, 76(9): 1522-1528.
15. Yamanaka H, Tamaki S, Ide Y, et al. Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study. Ann Rheum Dis, 2018, 77(2): 270-276.
16. Doherty M, Jenkins W, Richardson H, et al. Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. Lancet, 2018, 392(10156): 1403-1412.
17. Wright DF, Duffull SB, Merriman TR, et al. Predicting allopurinol response in patients with gout. Br J Clin Pharmacol, 2016, 81(2): 277-289.
18. Stamp LK, Chapman PT, Barclay M, et al. Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study. Ann Rheum Dis, 2017, 76(12): 2065-2070.
19. Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol, 2004, 31(12): 2429-2432.
20. Mitha E, Schumacher HR, Fouche L, et al. Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial. Rheumatology (Oxford), 2013, 52(7): 1285-1292.
21. Paulus HE, Schlosstein LH, Godfrey RG, et al. Prophylactic colchicine therapy of intercritical gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum, 1974, 17(5): 609-614.
22. Poiley J, Steinberg AS, Choi YJ, et al. A randomized, double-blind, active- and placebo-controlled efficacy and safety study of arhalofenate for reducing flare in patients with gout. Arthritis Rheumatol, 2016, 68(8): 2027-2034.
23. Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study. Ann Rheum Dis, 2011, 70(7): 1264-1271.
24. Schumacher HR, Evans RR, Saag KG, et al. Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. Arthritis Care Res (Hoboken), 2012, 64(10): 1462-1470.
25. Sundy JS, Schumacher HR, Kivitz A, et al. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. J Rheumatol, 2014, 41(8): 1703-1711.
26. Solomon DH, Liu CC, Kuo IH, et al. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis, 2016, 75(9): 1674-1679.
27. Yu J, Qiu Q, Liang L, et al. Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting. Mod Rheumatol, 2018, 28(2): 339-344.
28. Hill EM, Sky K, Sit M, et al. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol, 2015, 21(3): 120-125.
29. Taylor TH, Mecchella JN, Larson RJ, et al. Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med, 2012, 125(11): 1126-1134.
30. Feng X, Li Y, Gao W. Significance of the initiation time of urate-lowering therapy in gout patients: A retrospective research. Joint Bone Spine, 2015, 82(6): 428-431.
31. Goldfien R, Pressman A, Jacobson A, et al. A pharmacist-staffed, virtual gout management clinic for achieving target serum uric acid levels: a randomized clinical trial. Perm J, 2016, 20(3): 15-234.
32. Mikuls TR, Cheetham TC, Levy GD, et al. Adherence and outcomes with urate-lowering therapy: a site-randomized trial. Am J Med, 2019, 132(3): 354-361.
33. de Lautour H, Taylor WJ, Adebajo A, et al. Development of preliminary remission criteria for gout using Delphi and 1000 minds consensus exercises. Arthritis Care Res (Hoboken), 2016, 68(5): 667-672.
34. González-Galarza FF, Takeshita LY, Santos EJ, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res, 2015, 43(Database issue): D784-788.
35. Jutkowitz E, Dubreuil M, Lu N, et al. The cost-effectiveness of HLA-B*5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum, 2017, 46(5): 594-600.
36. Keller SF, Lu N, Blumenthal KG, et al. Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study. Ann Rheum Dis, 2018, 77(8): 1187-1193.
37. White WB, Saag KG, Becker MA, et al. Cardiovascular safety of febuxostat or allopurinol in patients with Gout. N Engl J Med, 2018, 378(13): 1200-1210.
38. Zhang M, Solomon DH, Desai RJ, et al. Assessment of cardiovascular risk in older patients with gout initiating febuxostat versus allopurinol: population-based cohort study. Circulation, 2018, 138(11): 1116-1126.
39. Foody J, Turpin RS, Tidwell BA, et al. Major cardiovascular events in patients with gout and associated cardiovascular disease or heart failure and chronic kidney disease initiating a xanthine oxidase inhibitor. Am Health Drug Benefits, 2017, 10(8): 393-401.
40. Saag KG, Fitz-Patrick D, Kopicko J, et al. Lesinurad combined with allopurinol: a randomized, double-blind, placebo-controlled study in gout patients with an inadequate response to standard-of-care allopurinol (a US-based study). Arthritis Rheumatol, 2017, 69(1): 203-212.
41. Major TJ, Topless RK, Dalbeth N, et al. Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population-based cohorts. BMJ, 2018, 363: k3951.
42. Nguyen UD, Zhang Y, Louie-Gao Q, et al. Obesity paradox in recurrent attacks of gout in observational studies: clarification and remedy. Arthritis Care Res (Hoboken), 2017, 69(4): 561-566.
43. Waldman B, Ansquer JC, Sullivan DR, et al. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. Lancet Diabetes Endocrinol, 2018, 6(4): 310-318.
44. FitzGerald JD, Mikuls TR, Neogi T, et al. Development of the American college of rheumatology electronic clinical quality measures for gout. Arthritis Care Res (Hoboken), 2018, 70(5): 659-671.
45. Khan AA, Quinn TJ, Hewitt J, et al. Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta- analysis. Age (Dordr), 2016, 38: 16.
46. Levy G, Shi JM, Cheetham TC, et al. Urate-lowering therapy in moderate to severe chronic kidney disease. Perm J, 2018, 22: 17-142.
47. Abeles AM, Pillinger MH. Gout and cardiovascular disease: crystallized confusion. Curr Opin Rheumatol, 2019, 31(2): 118-124.

Chinese Journal of Evidence-Based Medicine

2020 American College of Rheumatology guideline for the management of gout: an interpretation

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