Amir Qaseem, MD, PhD, MHA; Russell P. Harris, MD, MPH; Mary Ann Forciea, MD; for the Clinical Guidelines Committee of the American College of Physicians (*)
Note: Clinical practice guidelines are “guides” only and may not apply to all patients and all clinical situations. Thus, they are not intended to override clinicians' judgment. All ACP clinical practice guidelines are considered automatically withdrawn or invalid 5 years after publication, or once an update has been issued.
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations.
Financial Support: Financial support for the development of this guideline comes exclusively from the ACP operating budget.
Disclosures: Dr. Barry reports grants and personal fees from the Informed Medical Decisions Foundation and Healthwise outside the submitted work. Dr. Boyd reports royalties from UpToDate outside the submitted work. Authors not named here have disclosed no conflicts of interest. Authors followed the policy regarding conflicts of interest described at www.annals.org/aim/article/745942. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0570. All financial and intellectual disclosures of interest were declared, and potential conflicts were discussed and managed. Dr. Manaker was recused from voting on this guideline because of an active indirect financial conflict. Dr. McLean was recused from voting on this guideline because of an inactive direct financial conflict. A record of disclosures of interest and management of conflicts of interest is kept for each Clinical Guidelines Committee meeting and conference call and can be viewed at www.acponline.org/about-acp/who-we-are/leadership/committees-boards-councils/clinical-guidelines-committee/disclosure-of-interests-for-clinical-guidelines-committee.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Qaseem: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Dr. Harris: University of North Carolina School of Medicine, 725 Martin Luther King Boulevard, Chapel Hill, NC 27599-7590.
Dr. Forciea: University of Pennsylvania Health System, 3615 Chestnut Street, Philadelphia, PA 19104.
Author Contributions: Conception and design: A. Qaseem, R.P. Harris, M.A. Forciea, T.D. Denberg, M.J. Barry.
Analysis and interpretation of the data: A. Qaseem, R.P. Harris, M.A. Forciea, M.J. Barry, C. Boyd, N. Fitterman, L.L. Humphrey, D. Kansagara, S. Vijan, T. Wilt.
Drafting of the article: A. Qaseem, R.P. Harris, M.A. Forciea, T.D. Denberg.
Critical revision of the article for important intellectual content: R.P. Harris, T.D. Denberg, M.J. Barry, C. Boyd, R.D. Chow, N. Fitterman, L.L. Humphrey, D. Kansagara, S. Vijan, T. Wilt.
Final approval of the article: A. Qaseem, R.P. Harris, M.A. Forciea, T.D. Denberg, M.J. Barry, C. Boyd, R.D. Chow, N. Fitterman, L.L. Humphrey, D. Kansagara, S. Vijan, T. Wilt.
Statistical expertise: A. Qaseem.
Administrative, technical, or logistic support: A. Qaseem.
Collection and assembly of data: A. Qaseem, R.P. Harris.
The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout.
Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms.
The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout.
ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence)
ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence)
ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence)
ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence)
Table 1. Pharmacologic Agents for Treatment of Gout
Table 2. The American College of Physicians' Guideline Grading System*
Summary of the American College of Physicians guideline on management of acute and recurrent gout.
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Vanya D. Wagler, DO; Aaron W. Pumerantz, DO
Rheumatology Section, Department of Medicine, William Beaumont Army Medical Center, El Paso, Texas
November 8, 2016
Clinical Practice Guidelines for Management of Acute and Recurrent Gout
We note with interest the newly released clinical practice guidelines for management of gout by Qaseem, et al (1). Given the prevalence of gout, significant disease burden, and the availability of potentially curative therapies, it is imperative that primary care physicians and rheumatologists manage chronic gout skillfully and purposefully. In light of existing clinical practice guidelines by the American College of Rheumatology (2) and the European League Against Rheumatism (3) recommending a “treat to target” approach for chronic urate-lowering therapy, it is surprising to see new ACP guidelines suggesting an alternative “treat to avoid symptoms” paradigm. While the prospect of administering urate-lowering therapy without monitoring serum urate may be alluring, it would be a step backward given our current understanding of gout pathophysiology, as hyperuricemia appears to be directly responsible for causing gout (4). The vast majority of patients with gout can achieve disease remission when an aggressive “treat to target” approach is used; it remains unclear whether an alternative approach would be equally as effective. Benefits of monitoring serum urate during therapy include the potential for dose adjustment based on variabilities in individual response to medication, verifying medication adherence, and the ability to prevent future flares by targeting a specific serum urate goal. Implicit in the “treat to avoid symptoms” approach is the assumption that alleviating symptoms is the primary reason for employing urate-lowering therapy. We would suggest that current symptoms provide only part of the impetus for gout therapy and that other clinical features may be just as compelling. For example, gouty erosions on radiography or a history of tophaceous disease of any kind should be sufficient reason to treat hyperuricemia aggressively, regardless of current symptoms. We also observe that although dramatic symptoms are typical of early gout, chronic gouty arthritis can at times be relatively asymptomatic during intercritical periods even while joint inflammation (as demonstrated by ultrasonography) is ongoing (5). For these reasons, symptom-based therapy alone is inadequate and could well result in increased chronic morbidity from gout due to less aggressive treatment. We agree that future gout research should focus on better establishing optimal serum urate-lowering goals, and should consider the benefits of a symptom-based treatment paradigm, but we believe it is premature to suggest “treat to avoid symptoms” as a viable strategy at this time. 1. Qaseem A, McLean R, Starkey M, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Diagnosis of acute gout: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016. [Epub ahead of print]. doi:10.7326/M16-0569. 2. Khanna D, Fitzgerald JD, Khanna PP, et al., American College of Rheumatology. 2012 American College of Rheumatology Guidelines for the management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012;64:1431–46.3. Richette P, Doherty M, Pascual E, et al., 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis Published Online First. doi:10.1136/annrheumdis-2016-2097074. Schett G, Schauer C,Hoffmann M, et al. Why does the gout attack stop? A roadmap for the immune pathogenesis of gout. RMD Open 2015;1:e000046. doi:10.1136/rmdopen-2015-000046.5. Thiele RG, Schlesinger N. Ultrasonography shows active inflammation in clinically unaffected joints in chronic tophaceous gout. Arthritis Rheum 2009;59(9 Suppl):S1512.
David Erk MD FACP
Sage Primary Care, Casper WY
January 15, 2017
Questions regarding treatment of gout
Question 1: What is the recommendation for duration of initial treatment of a patient with an acute gout flare, if that patient will not be receiving a uric acid lower medication?Question 2: What is the recommendation for the timing of starting a uric acid lowering medication following an acute gout flare?
Russell P. Harris, MD, MPH, Robert M. McLean, Amir Qaseem, MD, PhD, MHAMD,
March 8, 2017
IN RESPONSE: We agree with Drs. Wagler and Pumerantz that clinicians need to manage gout effectively. The ACP Guidelines on Diagnosis and Management of Gout (1, 2) were developed meeting the current standards for clinical guidelines by set forth by GIN and IOM (3, 4) and using the best available evidence rather than relying on expert-based opinion. While Drs. Wagler and Pumerantz advocate for a treat-to-target approach, unfortunately there is currently insufficient evidence to support some of their statements about aggressive treatment, treating beyond clinical symptoms, or serum urate monitoring. This issue has been acknowledged in a recent article in a rheumatology journal summarizing that the treat-to-target strategy is based on indirect evidence and no trials (5). The recommendation in our guideline highlighted the lack of evidence and stated uncertainty about the treat-to-target strategy. We did not recommend against it, rather we recommended a shared decision making approach between informed clinicians and patients. We suggest that clinicians talk to their patients and set realistic expectations after a discussion of what is known and unknown about the benefits, harms, costs of a treat-to-target strategy. It is most important to take patient preferences into account when making the decision. When developing our recommendations, we weigh the incremental benefits and harms of an intervention. In cases of uncertainty similar to this one (i.e., a chronic condition that may or may not recur), we suggest that the burden of proof of benefit lies with those who propose a more “aggressive” strategy rather than vice versa. For any intervention to be implemented, first we should have evidence of at least moderate certainty of the magnitude of benefit. Although Drs. Wagler and Pumerantz point out various potential benefits of an “aggressive” strategy, they do not discuss potential harms and costs, including more office visits, additional testing, increased burden of taking medication daily, increased probability of medication side effects (as dose is escalated), increased labeling, and higher costs without clear evidence of improved outcomes.Although serum urate level is certainly associated with gout flares, there are clearly other, unknown factors at work. There is still much uncertainty for an individual patient after a gout flare about whether he or she would have further flares, how many and of what severity. We do not have any recommendation regarding monitoring during urate-lowering treatment, as no studies assessed monitoring. We question what the clinician should monitor during treatment: patient symptoms or serum urate levels via a blood test? Until there is evidence to the contrary, we favor a careful consideration of which monitoring strategy the patient prefers. We agree that our assumption is that avoiding symptoms is the primary reason for treatment. We think that it is an appropriate approach until there is evidence that longer term patient-centered outcomes are improved to a substantial degree by a different strategy. We also remind the readers that our guideline is not addressing patients with tophi or other serious underlying co-morbidities.Regarding Dr. Erk’s questions about initial treatment duration and timing of uric acid lowering therapy, unfortunately there is insufficient evidence to answer these questions. In the absence of clear direction from evidence, we recommend that clinical judgement and experience continue to play a role in these decisions.Russell P. Harris, MD, MPH University of North Carolina School of Medicine, Chapel Hill, NC Robert M. McLean, MD Yale School of Medicine, New Haven, CT Amir Qaseem, MD, PhD, MHAAmerican College of Physicians, Philadelphia, PA References1. Qaseem A, Harris RP, Forciea M, for the Clinical Guidelines Committee of the American College of P. Management of acute and recurrent gout: A clinical practice guideline from the american college of physicians. Annals of Internal Medicine. 2017;166(1):58-68.2. Qaseem A, McLean RM, Starkey M, Forciea M, for the Clinical Guidelines Committee of the American College of P. Diagnosis of acute gout: A clinical practice guideline from the american college of physicians. Annals of Internal Medicine. 2017;166(1):52-7.3. Institute of MedicineClinical Practice Guidelines We Can Trust.Washington, DC. National Academies Pr 2011.4. Qaseem A, Forland F, Macbeth F, et al. Guidelines international network: Toward international standards for clinical practice guidelines. Annals of Internal Medicine. 2012;156(7):525-31.5. Kiltz U, Smolen J, Bardin T, Cohen Solal A, Dalbeth N, Doherty M, et al. Treat-to-target (T2T) recommendations for gout. Annals of the Rheumatic Diseases. 2016.
Qaseem A, Harris RP, Forciea MA, for the Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017;166:58-68. doi: 10.7326/M16-0570
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Published: Ann Intern Med. 2017;166(1):58-68.
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