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EXTENDED REPORT
Treat-to-target (T2T) recommendations for gout
U Kiltz,
1
J Smolen,
2
T Bardin,
3
A Cohen Solal,
4
N Dalbeth,
5
M Doherty,
6
B Engel,
7
C Flader,
1
JKay,
8
M Matsuoka,
9
F Perez-Ruiz,
10
G da Rocha Castelar-Pinheiro,
11
K Saag,
12
A So,
13
J Vazquez Mellado,
14
M Weisman,
15
T H Westhoff,
16
H Yamanaka,
17
J Braun
1
ABSTRACT
Objectives The treat-to-target (T2T) concept has been
applied successfully in several inflammatory rheumatic
diseases. Gout is a chronic disease with a high burden
of pain and inflammation. Because the pathogenesis of
gout is strongly related to serum urate levels, gout may
be an ideal disease in which to apply a T2T approach.
Our aim was to develop international T2T
recommendations for patients with gout.
Methods A committee of experts with experience in
gout agreed upon potential targets and outcomes,
which was the basis for the systematic literature search.
Eleven rheumatologists, one cardiologist, one
nephrologist, one general practitioner and one patient
met in October 2015 to develop T2T recommendations
based on the available scientific evidence. Levels of
evidence, strength of recommendations and levels of
agreement were derived.
Results Although no randomised trial was identified in
which a comparison with standard treatment or an
evaluation of a T2T approach had been performed in
patients with gout, indirect evidence was provided to
focus on targets such as normalisation of serum urate
levels. The expert group developed four overarching
principles and nine T2T recommendations. They
considered dissolution of crystals and prevention of flares
to be fundamental; patient education, ensuring
adherence to medications and monitoring of serum urate
levels were also considered to be of major importance.
Conclusions This is the first application of the T2T
approach developed for gout. Since no publication
reports a trial comparing treatment strategies for gout,
highly credible overarching principles and level D expert
recommendations were created and agreed upon.
INTRODUCTION
Gout is caused by deposition of monosodium urate
(MSU) crystals within joints in the setting of
chronic hyperuricaemia.
1
It affects 1%–2% of
adults in developed countries and is the most
common type of inflammatory arthritis worldwide.
Epidemiological data are consistent with a rise in
the prevalence and incidence of gout.
23
Nutrition
and genetic polymorphisms of renal transporters of
urate and other genes seem to be the main causal
factors of primary gout. Gout and hyperuricaemia
are associated with hypertension, diabetes mellitus,
metabolic syndrome and renal and cardiovascular
diseases.
145
There is a strong link between gout
and increased risk of death from all causes and
cardiovascular diseases.
6
The economic burden of
gout is considerable.
7
Gout is a common clinical problem encountered
by both general and specialist clinicians. The key
principles of gout management include establishing
adefinitive diagnosis, treating acute attacks
promptly and using urate-lowering therapies (ULTs)
appropriately to dissolve MSU crystals to eventually
prevent further attacks and joint damage. When
serum urate concentrations are lowered below the
saturation point of MSU, new crystal formation is
prevented, existing crystals dissolve and gout can
be cured. The ‘gold standard’diagnostic test for
gout remains the identification of MSU crystals by
polarised light microscopy in synovial fluid cells or
in a tophus.
8
Non-steroidal anti-inflammatory drugs (NSAIDs)
and colchicine remain the most widely recom-
mended systemic drugs to treat acute attacks.
910
In
some patients, especially those with comorbidities
that preclude NSAID use, oral glucocorticoids
(GCs) may represent an alternative. Joint aspiration
and injection of GC is recommended where feas-
ible, as in most hospital settings.
11–13
Patient educa-
tion, appropriate advice regarding lifestyle and
treatment of comorbidities are important in the
management of patients with gout.
14
Many different recommendations on the man-
agement of gout have been published over the last
decades.
11–13 15–18
However, major questions, as
discussed below, remain.
19–22
In many areas of medicine, such as diabetes care
or cardiology, clear therapeutic targets have been
defined and the continuous effort to reach these
targets is standard practice.
23–28
More recently,
treatment targets have also been advocated for
rheumatoid arthritis (RA), spondyloarthritides
(SpA) including psoriatic arthritis (PsA) and sys-
temic lupus erythematosus, namely remission or
low disease activity.
29 30
These recommendations
have been based on insights gained from systematic
literature reviews (SLRs) of clinical trials.
31 32
The
successful application of a treat-to-target (T2T)
strategy in a rheumatologic disease was first
reported in RA and subsequently in PsA.
33 34
Much less information is currently available
regarding the value of defining therapeutic targets
for gout. Despite recently published treatment
recommendations
11–13 15 17 18
and some scientific
and therapeutic advances, such as the approval of
the first selective urate transporter inhibitor, a
variety of challenges, such as preventing recurrence
To cite: Kiltz U, Smolen J,
Bardin T, et al. Ann Rheum
Dis 2017;76:632–638.
Handling editor Tore K Kvien
►Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
annrheumdis-2016-209467).
For numbered affiliations see
end of article.
Correspondence to
Professor Juergen
Braun, Rheumazentrum
Ruhrgebiet, Herne D-44652,
Germany; juergen.braun@
elisabethgruppe.de
Received 1 March 2016
Revised 26 August 2016
Accepted 27 August 2016
Published Online First
22September2016
Recommendation
632 Kiltz U, et al. Ann Rheum Dis 2017;76:632–638. doi:10.1136/annrheumdis-2016-209467
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of attacks, remain when considering the current management of
patients with gout. These challenges exist, in part, because a
clear therapeutic target and strategies to reach such a target have
not yet been defined optimally. To improve the management of
gout in clinical practice, a core group was convened to discuss
and develop consensus recommendations aimed at defining a
treatment target and initiate a T2T programme for gout.
METHODS
Five rheumatologists from Europe and North America with
expertise in gout met in Athens in April 2014 and agreed on the
need to develop T2T recommendations for gout. A steering
committee was established, comprised of rheumatologists who
were identified based upon their expertise in gout, experience in
developing treatment recommendations, publication record and
participation in clinical trials of novel therapies for gout.
Through face-to-face discussions and email communications,
they agreed to use a four-step methodology:
(i) define treatment targets and outcomes
(ii) perform a systematic literature review (SLR)
(iii) evaluate the findings of the SLR within the steering
committee
(iv) develop final recommendations for T2T for gout with a
larger task force.
Definition of target and outcomes: The steering committee
determined potential targets and outcomes by email communi-
cation. There was no limitation to the number of targets and
outcomes that could be proposed. Each target and outcome was
then voted upon by email communication using a Delphi
method; those that were supported by at least 75% of the
members were accepted.
Systematic literature review: Search terms for the SLR were for-
mulated based on the PICO (participant intervention, control,
outcome) system, taking into account the targets and outcomes
(see online supplementary table S1). Authors UK and CF per-
formed the SLR using Medline, EMBASE and Cochrane, focus-
ing on strategy trials in which therapeutic adjustments were
made according to prespecified timelines and/or prespecified
endpoints. Detailed inclusion and exclusion criteria and the list
of search strings are shown in online supplementary tables
S1 and S2. All English language human studies were evaluated
based on an iterative process with screening of titles, followed
by screening of abstract and completed by a full-text review. The
results of the SLR were graded for the level of evidence pro-
vided by the Oxford Centre for Evidence-Based Medicine on a
scale of 1–5.
35
We did not exclude studies based on quality.
Evaluation: The findings of the SLR were presented to the steer-
ing committee at a meeting in Herne, Germany, in June 2015.
On this basis, the steering committee formulated a provisional
set of recommendations according to European League Against
Rheumatism standardised operating procedures fulfilling the
AGREE criteria.
36 37
The level of evidence and strength of each
recommendation were determined and categorised as A
(highest) to D (lowest) on the basis of the SLR. The preliminary
recommendations were distributed to the international task
force, which consisted of gout experts from North America,
South America, Europe, Oceania (New Zealand) and Asia; a
nephrologist, a cardiologist, a general practitioner and a patient
with gout.
Development of final recommendations: The international mul-
tispecialty task force met in Herne, Germany, in October 2015,
to discuss the T2T approach in detail and develop the final
recommendations. The background of the T2T approach was
discussed and the preliminary recommendations developed by
the steering committee were presented. These were reformu-
lated and reordered, until each recommendation received a
majority of at least 75% of the votes by using a nominal consen-
sus technique. After the face-to-face meeting, the final recom-
mendations were circulated by email to the entire task force for
final comments. Only suggestions intended to improve the
clarity of wording or to address redundancies were considered;
no changes to the content were allowed at this point. The task
force then voted by email on the level of agreement with each
recommendation using a numerical rating scale of 0–10, with
the highest value indicating the greatest level of agreement.
RESULTS
Definition of target and outcomes: Six possible treatment
targets and five possible outcome domains were identified by
the steering committee (table 1). The final list includes four
targets and three outcomes about which a SLR should be
performed.
Systematic literature review: Of the initial 761 papers retrieved,
55 were selected for full-text review. No randomised trial was
identified in which a T2T approach had been evaluated in com-
parison with standard treatment (flow chart in online supple-
mentary figure S1 illustrates the selection process). However,
there was indirect evidence that optimal therapeutic approaches
help to control the disease.
38–42
The investigators showed that
control of serum uric acid levels (SUA) is optimised by providing
patient education, enhanced telephone access to expert advice,
upward titration of allopurinol, febuxostat or benzbromarone
and increased frequency of visits until the target SUA concentra-
tion was achieved.
14
Other urate-lowering agents, such as lesi-
nurad, might also be used but strategy trials employing these
drugs were not identified in the SLR. Successful reduction of
SUA levels by upward titration of ULT, but without prescheduled
therapeutic adaptation processes, has been demonstrated in
many other trials.
38–40 43 44
Patients with gout exhibited a
higher velocity of tophus size reduction when reaching a serum
urate concentration below the saturation point of MSU early
and maintaining that level.
39 45 46
Table 1 Voting on treatment targets and outcomes
Agreement* (%) Accept
Treatment targets
Serum urate level 90 Yes
Time to resolution of inflammation 40 No
Amount/reduction/absence of tophi
(burden of deposition)
90 Yes
Pain reduction 90 Yes
Prevention/absence of attacks 100 Yes
Adherence to medication 60 No
Outcome
Clinical: Pain, joint count, number of attacks/year 100 Yes
Laboratory: Serum urate level, CRP, ESR, serum
creatinine
90 Yes
Functional: SF-36 (physical component score) 60 No
Imaging: Radiographs (specific signs), ultrasound
(tophi), dual energy CT (urate deposition)
60 No
PRO: QoL, SF-36, work status, productivity, work
days off, absenteeism/presenteeism
80 Yes
*10 members of the steering committee voted.
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PRO, patient-reported
outcomes; QoL, quality of life; SF-36, short-form 36.
Recommendation
633
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Significant discussion also focused on asymptomatic hyperuri-
caemia. Although intervention to treat severe asymptomatic
hyperuricaemia has been recommended in Japan,
47
there is
inadequate evidence to support its appropriateness. The task
force members agreed that it could be valuable to develop an
appropriate strategic approach to the treatment of asymptomatic
hyperuricaemia. However, they concurred that there is no evi-
dence to suggest that the treatment target for asymptomatic
hyperuricaemia should be any different than that for gout.
Evaluation: Based on the SLR, preliminary recommendations
(three overarching principles and eight recommendations) were
formulated by the steering committee.
Recommendations: The preliminary recommendations were
reformulated and reordered by the task force during a meeting
in October 2015, yielding four overarching principles and nine
recommendations. The final consensus recommendations are
listed in table 2 and discussed in detail below.
Overarching principles
Since gout is a potentially curable disease, the central guiding
principles are to reduce serum urate levels and to maintain a
target serum urate level. To achieve these goals, patients must be
educated completely about the disease and should participate in
the decision-making process. The overarching principles, which
are listed in table 2, address the following aspects:
A. Gout as a chronic and serious disease that can be treated
effectively.
6
B. The importance of reducing and maintaining serum urate
below a defined target.
C. The requirement for patient education about all aspects of
the disease and for shared decision-making with the
patient.
14
D. The need for long-term adherence to urate-lowering therapy.
Recommendations
The main points discussed were as follows:
(i) Both providers and patients should be educated about the
disease and its treatment.
(ii) Patients and healthcare providers should make treatment
decisions together.
(iii) The primary treatment approach is to reduce and maintain
serum urate at a level sufficient to effect dissolution of MSU
crystals.
(iv) Modifying lifestyle and monitoring renal function are
important.
It was decided to not differentiate between ‘acute’and
‘chronic’gout, since both belong to the spectrum of a single
disease.
All recommendations are presented in table 2 together with the
level of supporting evidence, the strength of the recommendation
and the level of agreement. Of note and in line with the SLR, the
level of evidence was low (D) for most of the recommendations.
This lack of evidence supporting how best to treat gout likely is
one of the main reasons why it is often difficult to treat the disease
successfully and especially to maintain patients free of disease
activity over the long term. In the presence of comorbidities, such
as renal impairment, the aim of low disease activity is much more
complicated to reach which was the basis to recommend assess-
ment of renal function on a regular basis. It also provides the basis
for the research agenda, since much more information is needed
to develop highly valid treatment recommendations.
Interestingly and despite the low level of evidence, there was
a very high level of agreement among task force members, with
six of the nine recommendations achieving agreement levels of
9.5 or more on a 10-point scale. This suggests that the experts
from different fields and the patient with gout on the task force
were quite convinced of the validity of the statements. Only rec-
ommendation #5, which deals with prophylaxis, had a lower
level of agreement (8.3). This lower level of agreement was due
to the absence of prospectively acquired data regarding the
appropriate duration of prophylaxis.
A research agenda was also developed (table 3). It was
decided to re-evaluate the current proposals at a future meeting
attended by several stakeholders, including more patients.
Therefore, the present recommendations should be regarded as
a basis for further discussion and amendment.
Table 2 Recommendations to treat-to-target gout
LoE GoR SoR
Overarching principles
A Gout is a chronic and serious disease with impaired quality of life and reduced life expectancy that can be treated effectively. 9.5±0.9
B Reducing and maintaining serum urate below a defined target is mandatory to eliminate urate crystals and improve patient outcomes. –– 9.8±0.7
C Successful management of gout requires education about all aspects of the disease and full involvement of the patient in shared
decision-making.
–– 9.7±0.7
D Long-term adherence to urate-lowering therapy is essential for an optimal outcome. –– 9.4±0.8
Recommendations
1 Serum urate must be measured regularly and urate-lowering therapy should be adjusted to attain the therapeutic target. 2 B 9.8±0.6
2 A serum urate level <6 mg/dL (<360 mmol/L) should be targeted and maintained in all patients with gout 1 A 9.5±0.9
3 In patients with severe gout, such as those with tophi or frequent attacks, the target should be a serum urate level <5 mg/dL (<300 mmol/L)
until clinical remission is achieved
5 D 9.2±1.5
4 Acute attacks should be treated promptly with anti-inflammatory medications, taking safety issues into consideration 5 D 9.9±0.5
5 Prophylaxis against attacks should be initiated and continued for at least 6 months after starting urate-lowering therapy. 5 D 8.3±1.7
6 In all patients with gout, renal function should be assessed at the time of diagnosis and then monitored regularly. 5 D 9.6±0.7
7 Comorbidities associated with gout may influence therapy and outcomes and should be assessed regularly and managed 5 D 9.5±0.8
8 Modifiable risk factors should be addressed primarily through patient education and support. 5 D 9.2±1.5
9 Information about gout and its management should be made readily available to patients by their healthcare professionals. 5 D 9.7±0.7
SoR on a 0–10 scale with 0=no agreement at all and 10=very strong agreement.
GoR, grade of recommendation; LoE, level of evidence; SoR, strength of recommendation.
Recommendation
634 Kiltz U, et al. Ann Rheum Dis 2017;76:632–638. doi:10.1136/annrheumdis-2016-209467
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DISCUSSION
This is the first initiative to propose overarching principles and
recommendations for the management of gout using a T2T strat-
egy. Since this approach has been applied to several other rheum-
atic diseases,
29 30
we considered it important to employ this
successful concept in gout—a disease for which a major target can
be defined easily and in which outcomes depend upon
maintenance of the serum urate concentration at a low level.
However, the scope of the recommendations is focusing on tar-
geted treatment options and on a broader concept including
recommendations for prophylaxis against attacks and monitoring
of comorbidities. This rationale is based on the fact that aiming for
low serum urate concentrations must be supported by anti-
inflammatory strategies and/or prevention of comorbidities.
Table 3 Research agenda
No Research question Comment with respect to a T2T approach
1 What is the optimal target serum urate level to manage gout? SUA level of <6 mg/dL (<360 mmol/L) or <5 mg/dL (<300 mmol/L) are not data
driven, a valid and reliable cut-off will facilitate a targeted approach.
2 Is the current recommended target serum urate level a valid endpoint? This important question should be addressed by taking the scientific evidence and
the patient point of view into account. A laboratory parameter might not
adequately reflect the signs and symptoms of the patient.
3 How often should the serum urate level be measured to optimally control disease? Definition of time intervals to measure SUA is mandatory to adapt therapy based
on the treatment target.
4 How does frequency of serum urate measurement impact on the management of
patients with gout?
Frequency of measurements should be feasible and aim to avoid overassessment
and underestimation. No trial exists at all to address impact of measurement on
the management of patients with gout.
5 Are very low serum urate levels dangerous (such as by causing neuropsychiatric
disease, eg, dementia)?
The knowledge about valid upper and lower thresholds of SUA is mandatory to
follow a T2T approach.
6 What are the consequences of lowering serum urate levels? A T2T approach in patients with gout must address potential harmful consequences
(like occurrence of acute attacks while initiating ULT).
7 Is it possible to develop a composite disease activity measure that might serve as
a better target for management of gout disease activity in clinical practice?
(GDAI=gout disease activity index).
More than the SUA level influences disease activity in patients with gout.
Therefore, it seems likely that a composite instrument is addressing the patients
need more accurate.
8 Does an elevated serum urate level cause chronic kidney disease? The relationship between gout and chronic kidney disease is bidirectional and
whether it is a causal relation or an association is still a matter of debate. It still
has to be shown that lowering of SUA prevents renal function from further
deterioration (and vice versa).
9 How often should renal function be measured? Frequency of measurements should be feasible and aim to avoid overassessment
and underestimation.
10 What is the optimal management of gout in patients with multiple comorbidities? Determination of treatment target and strategy to adapt the therapy depends on
occurrence of many factors, that is comorbidities. Multidisciplinary management
should agree upon an achievable treatment target.
11 Is there any diagnostic utility to aspirating joints in patients with intercritical gout? The absence of crystals in the synovial fluid is one of the targets that are linked to
lowering SUA. Serial joint aspiration studies confirmed the disappearance of
crystals with effective ULT. The value of this laboratory finding in patients with
absent of gout attacks is questionable.
12 Should monitoring by ultrasound or CT be used in gout? Diagnostic utility of imaging procedure has been studied to diagnose but has not
been extensively studied to monitor the disease. Since deposition of MSU crystals
in the tissue is a consequence of increased levels of SUA imaging procedure might
serve as a surrogate marker in the management of gout.
13 How is the treatment of both acute and chronic manifestations of gout best
integrated into a T2T strategy?
Whether the artificial partition between acute and chronic stages is helpful in
treating patients with gout is still a matter of debate. However, research on
implementations strategies focused on setting a target and adapting the treatment
accordingly is strongly needed.
14 What is the optimal timing of initiating treatment for acute gout attacks? The start of the treatment and prescheduled adaptation process within the
treatment strategy is a crucial point that is not yet well defined in studies.
Especially, initiating ULT during an acute gout attack remains a matter of debate.
15 What is the optimal strategy to eliminate tophi? The outcome ‘size and number of tophi’is difficult to assess. There is no consensus
about the optimal tool to assess this outcome reliable and sensitive to change.
However, assessment of tophi is crucial to assess adaptation process within the
treatment strategy.
16 Should urate lowering therapy be initiated after the first gout attack? Whether ULT therapy should be initiated after the first gout attack or after a
subsequent attack remains controversial. Studies should be conducted to address
this question, so as to optimise treatment
17 Is there any effect of treating asymptomatic hyperuricaemia? Studies are warranted to assess whether T2T approach is also applicable for
patients with asymptomatic hyperuricaemia.
18 What is the role of surgery in the treatment of tophi? Pharmacological interventions are the cornerstone in the T2T approach, but the
value of surgical procedures has not been investigated.
19 Does a T2T approach improve the adherence of patients to their treatment? Adherence to treatment is low in patients with gout. In a T2T approach, patients
do have increased visits at least in the beginning of their disease. One important
question is whether this approach is increasing the adherence of patients to their
treatment
MSU, monosodium urate; SUA, serum uric acid levels; T2T, target-to-target; ULT, using urate-lowering therapy.
Recommendation
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After discussion about asymptomatic hyperuricaemia, the
group decided not to make recommendations regarding treat-
ment of hyperuricaemia in the absence of musculoskeletal symp-
toms because of inadequate evidence. One major concern,
which was raised during this discussion, was that treatment
targets for asymptomatic hyperuricaemia need to be defined.
Further research on this topic is warranted and should be con-
ducted in collaboration with cardiologists and nephrologists.
A T2T approach is based on assessing disease activity or sever-
ity. Neither is defined for patients with gout. The term ‘severity’
is inexact when referring to patients with gout and reflects a
variety of parameters, such as frequency of attacks, number of
swollen joints, number and size of tophi and presence of
comorbidities. No threshold has been defined to differentiate
between severe and mild disease states. Some progress has been
made in establishing disease activity scores for gout. Recently,
the KING study group proposed a new disease activity score for
gout including flare, SUA, pain, global activity assessment, joint
count and measure of tophi.
48
However, assessment of outcome domains is not yet standar-
dised in trials with gout patients. Several processes have been
implemented within OMERACT to endorse measures of
outcome. Pain, joint count and patient global assessment are the
recommended outcome measures for patients with acute gout,
whereas these three outcome measures with the addition of
activity limitation are the outcome measures recommended for
patients with chronic gout.
49 50
There is sufficient evidence to
support measures of pain, joint tenderness and swelling as ful-
filling the requirements of the OMERACT filter.
51
However,
almost no appreciable impact of the OMERACT-proposed
domains could be detected in our SLR.
52
Initially, we discussed possible treatment targets that should
be able to reflect when patients are in remission. The final target
list includes pain and SUA levels, as well as the absence of
attacks and tophi, as potential parameters to define remission in
patients with gout. Remission as a separate variable was not
included in our list of treatment targets because no formal deci-
sion has yet been made about the set of variables proposed by
OMERACT in 2014 to define remission. The publication of pre-
liminary remission criteria for gout in 2016 supports the
OMERACT group’s recommendation of variables to define
remission.
53
Because of the lack of strategy trials in gout, existing thera-
peutic recommendations are rather vague. For example, clini-
cians need guidance regarding the strategic use of
anti-inflammatory medications to balance potentially beneficially
and harmful effects in patients with acute attacks. However,
T2T recommendations are primarily generic in nature and do
not provide detailed management recommendations or focus on
specific drugs. Although some drugs are mentioned as examples,
the current recommendations do not endorse one drug over
others. With respect to the use of anti-inflammatory medica-
tions, our task force was not able to propose a specific sequence
of anti-inflammatory medications because trials to address this
question were never performed. Therefore, we propose a
research agenda to stimulate investigation into the unmet needs
in this area, including evaluation of the validity of a T2T strat-
egy in gout. This research agenda includes those questions that
were considered to be most important by the task force, but the
list obviously could be expanded in many areas, including
molecular aspects of pathophysiology and patient and physician
considerations.
This represents the first initiative to characterise gout as a
disease that should be managed by defining, achieving and
maintaining a treatment target to provide patients with the best
possible outcome. Its strengths are the inclusion of experts from
different areas of medicine and a gout patient representative on
the task force and the very high level of agreement that was
achieved for most of the recommendations. However, the
present activity was limited by the absence of published clinical
trials of strategies to treat gout. Thus, recommendations had to
be developed based solely upon expert opinion. Another limita-
tion of our approach might be our having limited our SLR to
only articles written in the English language. The prevalence of
gout and the need for a targeted therapeutic approach is also
increasing in less developed countries, such as those in Latin
America and in parts of Asia.
2
Further research is needed to apply our T2T recommenda-
tions in a clinical trial, comparing target-directed therapy with
routine care. The research agenda addresses many practical
questions, such as determining the frequency with which critical
blood tests should be performed, assessing the impact of
comorbidities and developing a gout disease activity index.
Given the low adherence to medication by patients with gout,
strategy trials, in which therapeutic adjustments are made
according to a prespecified timeline and/or prespecified end-
points, should address this critical issue. Presumably, strategy
trials will be able to include an adequate approach to control
for non-adherence.
54
A treatment strategy study will be import-
ant to improve the management of patients with gout and
should be initiated in the near future.
Author affiliations
1
Rheumazentrum Ruhrgebiet, and Ruhr University Bochum, Herne, Germany
2
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna,
Vienna, Austria
3
Assisitance Publique Hôpitaux de Paris Rheumatology Department, Lariboisière
Hospital, University Paris Diderot, Sorbonne Paris-Cité and INSERM, UMR 1132,
Paris, France
4
Research Medical Unit INSERM, Université Paris VII—Denis Diderot Assistance
Publique—Hôpitaux de Paris, Service de Cardiologie, Hôpital Lariboisière, Paris,
France
5
University of Auckland and Auckland District Health Board, Auckland, New Zealand
6
University of Nottingham, Nottingham, UK
7
Medical Faculty, Institute of General Practice and Family Medicine, University Bonn,
Bonn, Germany
8
UMass Memorial Medical Center and University of Massachusetts Medical School,
Worcester, Massachusetts, USA
9
Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
10
Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain
11
Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil
12
University of Alabama at Birmingham, Birmingham, Alabama, USA
13
Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois and University of
Lausanne, Lausanne, Switzerland
14
Servicio de Reumatología, Hospital General de México, México City, México
15
Division of Rheumatology, Cedars-Sinai Medical Center, David Geffen School of
Medicine at UCLA, Los Angeles, USA
16
Medical Department I, Marien Hospital Herne, Ruhr-University of Bochum, Herne,
Germany
17
Tokyo Women’s Medical University, Tokyo, Japan
Contributors All authors were fully involved in the T2T project. All authors
participated in the voting rounds, meetings and evaluation process. Authors UK and
CF did the SLR with judgement by JB. All authors actively participated in writing and
revising the paper.
Funding Financial support was requested and obtained from four companies
(Novartis, Berlin-Chemie Menarini, Astra-Zeneca and Ardea Bioscience).
Competing interests JS, MM, BE, JVM, TW, CF have no competing interests in
respect to this work. UK has received grant and research support and consultancy
fees from AbbVie, Chugai, MSD, Novartis, Pfizer, Roche and UCB. JB has received
honoraria for talks, advisory boards, paid consultancies and grants from studies from
Berlin-Chemie Menarini and Novartis. HY has received honoraria for talks, advisory
boards and grants from Abbvie, Astellas, AstraZeneca, BMS, Chugai,
Mitsubishi-Tanabe, Pfizer, Takeda, Teijin and UCB. GRCP has received honoraria for
consultancies from: AbbVie, AstraZeneca, BMS Hospira, Janssen, Pfizer, Roche,
Recommendation
636 Kiltz U, et al. Ann Rheum Dis 2017;76:632–638. doi:10.1136/annrheumdis-2016-209467
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RuiYi, and Sanofi-Aventis. ND has received consulting fees, speaker fees or grants
from the following companies: Takeda, Menarini, Teijin, Pfizer, Crealta, Cymabay,
Fonterra, Ardea Biosciences and AstraZeneca. MD has received honoraria for ad hoc
advisory boards for Ardea Biosciences, AstraZeneca, and Nordic Biosciences. Roche,
and AstraZeneca are funding a Nottingham University Investigator-led non-drug
study on gout. JK has received research funding paid to the University of
Massachusetts Medical School from Ardea Biosciences and consulting fees from
AstraZeneca; Novartis Pharmaceuticals Corporation; and Regeneron Pharmaceuticals.
KS has received consulting fees and served as a study investigator from Ardea/Astra,
Crealta, Takeda. TB has received consulting fees, speaker fees or grants from the
following companies: Ipsen Pharma, Menarini, Astrazeneca, Novartis, Sobi and
Cymabay.
Provenance and peer review Not commissioned; externally peer reviewed.
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