Spring 2021 (Volume 31, Number 1)
Treat to Target in Gout
By Abhijeet Danve, MD, FACP; and Tuhina Neogi, MD, PhD
Gout is the most common inflammatory arthritis affecting
42 million adults worldwide.1 Despite the
well understood pathophysiology and availability
of effective medications, gout care remains suboptimal and
adherence to therapy is poor. The central strategy in gout
management is to reduce serum urate (sUA) to below the
saturation threshold (6.8mg/dL= 408 μMol/L) to prevent
monosodium urate crystallization, thereby reducing risk of
gout flares and tophi. Because of this understanding of the
biology of gout, a treat-to-target (T2T) strategy has been
advocated by rheumatology societies, though this recommendation
has not been accepted by all organizations.2 A
T2T strategy involves management of the index condition
with frequent monitoring of disease activity while escalating
treatment to achieve a pre-specified quantifiable
therapeutic target, in contrast to using symptoms alone
as a gauge. A T2T strategy is used in a number of chronic
conditions including hypertension, diabetes, and rheumatoid
A criticism of T2T in gout has been whether sUA is an
adequate marker of clinical disease manifestations of flare
and tophi, but at least three randomized clinical trials
(RCTs) to date have provided insights into the effects of
lowering sUA to <6mg/dL (360 μMol/L) on clinically relevant
outcomes.6-8 A UK trial of nurse-led care that involved
specific use of a T2T strategy with dose titration compared
with usual care by general practitioners demonstrated
lower sUA, which was accompanied by decreased severity
and frequency of flares, reduction in tophi and improved
medication adherence.8 In a RCT carried out in participants
with early gout, there was a greater proportion
achieving sUA <6mg/dL (360 μMol/L) along with a greater
decrease in overall flare incidence in the febuxostat arm
compared with placebo.7 Similarly, Sundy et al. demonstrated
that use of pegloticase resulted in significantly
more participants achieving sUA <6mg/dL (360 μMol/L),
as well as a greater proportion with reduction in tophi and
flares compared with placebo.6 It is a fair concern that the
specific threshold of <6mg/dL (360 μMol/L) has not been
directly assessed in a RCT as being better than <6.8mg/dL
(408 μMol/L) or <5mg/dL (300 μMol/L), for example. Nonetheless,
these trials do provide support for lowering sUA
to sufficiently below the saturation threshold to achieve
improvements in the clinical outcomes of flares and tophi.
With consideration of these and other data in the comprehensive
evidence report, the American College of Rheumatology
(ACR) 2020 gout guidelines strongly recommended
a T2T strategy with urate-lowering therapy (ULT)
dose titration guided by serial sUA levels to achieve a target
of <6 mg/dL (360 μMol/L). It also recommended that
ULT titration should occur over a reasonable time frame
to prevent treatment inertia.9 The 2016 European League
Against Rheumatism (EULAR) recommendations for the
management of gout also supported use of a T2T strategy
with a goal sUA of <6mg/dL (360 μMol/L).10
In summary, there is now high-quality data available
combined with good understanding of gout’s pathophysiology,
and treatment guidelines to support T2T in gout.
Thus, rather than practicing “reactive” health care, a
proactive T2T approach can mitigate and prevent the longterm
sequelae of inadequately managed gout.
Abhijeet Danve, MD, FACP
Assistant Professor of Medicine,
Yale School of Medicine
New Haven, Connecticut
Tuhina Neogi, MD, PhD
Professor of Medicine,
Boston University School of Medicine
1. Safiri S, Kolahi AA, Cross M, et al. Prevalence, incidence, and years lived with disability due to gout
and its attributable risk factors for 195 countries and territories 1990-2017: A systematic analysis
of the global burden of disease study 2017. Arthritis Rheumatol. 2020; 72(11):1916-27.
2. Qaseem A, Harris RP, Forciea MA, 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(1):58-68.
3. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high
blood pressure in adults: report from the panel members appointed to the Eighth Joint National
Committee (JNC 8). JAMA. 2014; 311(5):507-20.
4. Yki-Jarvinen H, Kauppila M, Kujansuu E, et al. Comparison of insulin regimens in patients with
non-insulin-dependent diabetes mellitus. N Engl J Med.1992; 327(20):1426-33.
5. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis
(the TICORA study): a single-blind randomised controlled trial. Lancet. 2004; 364(9430):263-9.
6. Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of
chronic gout in patients refractory to conventional treatment: two randomized controlled trials.
JAMA. 2011; 306(7):711-20.
7. 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):2386-95.
8. 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):1403-12.
9. FitzGerald JD, Dalbeth N, Mikuls, et al. 2020 American College of Rheumatology Guideline for the
Management of Gout. Arthritis Rheumatol. 2020; 72(6):879-95.
10. 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.