‘Remission or, alternatively, low disease activity’ has been defined as the therapeutic target for spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was based on evidence levels of the lowest category.1 One of the highlights of this year’s European Congress of Rheumatology is the presentation of the updated treat-to-target (T2T) recommendations. With the aim of improving the definition of treatment targets, the task force re-evaluated the recommendations in light of new evidence from the past 5 years, and arrived at a single set of recommendations comprising 5 overarching principles and 11 recommendations that were applicable to both axial and peripheral SpA, including psoriatic arthritis (PsA).1 Although consensual definition of remission is still lacking, operational definitions for treatment targets are available, with Ankylosing Spondylitis Disease Activity Score (ASDAS) being the preferred measurement of disease activity for axial SpA (axSpA), and Disease Activity index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA being recommended for PsA.1 The 2017 update was published in Annals of the Rheumatic Diseases.1
“The T2T recommendations are following the principle that you have to define a target you want to reach and adapt management to reach this target. This is independent of the treatment you use to reach the target,” said Désirée van der Heijde, Professor of Rheumatology at Leiden University Medical Centre, who is the convenor of the recommendations task force. “[The 2017 version] enforces that it is important to set a target in shared decision with the patient, monitor the disease and act with adaptation of management if the target has not been reached in order to improve the outcome of SpA ”, she added.2
The T2T strategy has been widely used in the management of many disease areas such as diabetes and cardiology. In rheumatology, this principle was first applied in rheumatoid arthritis (RA) in 2010,3 in which a treatment target of remission or low disease activity was recommended based on insights gained from various clinical trials. Inspired by RA management, T2T strategy was also implemented in SpA in 2012.4
The original 2012 recommendation included 5 overarching principles and 11 recommendations (9 of which are related to the whole spectrum of SpA, and 2 were designed separately for axSpA, peripheral SpA and PsA). Similar to RA, it is recommended that “remission/inactive disease of musculoskeletal involvement (arthritis, dactylitis, enthesitis, axial disease), taking extra-articular manifestations into consideration”, should be the major treatment target for all forms of SpA (recommendation 1), and that “low/minimal disease activity may be an alternative treatment target” (recommendation 4).4 For axSpA, Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) plus acute phase reactants was the preferred measurement of disease activity (recommendation 10). Meanwhile, a clear definition of treatment target was lacking for peripheral SpA and PsA. Although these recommendations laid down the framework for future T2T management of SpA, unlike RA, none of them is based on hard evidence, due to the scarcity of strategic therapeutic trials available.4
For physicians, the 2017 update is most important in strengthening several 2012 recommendations by incorporating higher-quality evidence (Table 1), as Prof. van der Heijde described. “In the new update, 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA”.5
Based on new evidence from TICOPA trial, the EULAR task force affirms the recommendation of attaining low/minimal disease activity as an alternative treatment target in PsA. Of note, TICOPA is the first-in-disease randomized strategic trial that showed better clinical outcomes with tight disease control, i.e. therapy was consistently adapted to reach a prespecified target (MDA), when compared to conventional care in patients with early PsA (OR of ACR20 response at week 48=1.91; 95% CI: 1.03–3.55; p=0.0392).6 Given that the T2T group was associated with more adverse events in the TICOPA trial, the panel members also emphasized that “safety aspects have to be considered when using a T2T approach.”1
As for other forms of SpA, a solid evidence is still lacking: two T2T trials (TICOSPA and STRIKE) are currently ongoing for axSpA, and no trials were conducted for peripheral SpA apart from PsA. Nonetheless, the panel determined that “T2T approach could also improve outcomes in axial SpA, given the correlation of damage progression with disease activity.”1 With the support of indirect evidence, targeting remission/ inactive disease (recommendation 1) and, as an alternative, low/minimal disease activity (recommendation 4) remain the mainstay of T2T approach for the SpA spectrum.1
Another important change is the provision of a more specific recommendation for the measurement of disease activity.
After a heated debate, ASDAS is now the preferred assessment tool for axSpA, primarily due to the evidence showing that this score outperformed BASDAI plus CRP in discriminating syndesmophyte formation. The topic of discussion had been circling around the feasibility of getting all necessary parameters in routine clinical practice. Indeed, Maxime Dougados, Professor of Rheumatology at Cochin Hospital, Paris, who is also a member of the task force, cited a low rate (0.9%) of systematic collection of ASDAS in daily practice in Paris in the EULAR meeting.5,7 Nonetheless, ASDAS came out as the preferred measure in the end because it is associated with better outcomes, as explained by Prof. van der Heijde.5
For PsA, the recommendations for DAPSA and MDA are now explicitly mentioned, although other instruments await further evaluation.1 MDA is considered as a useful target as it is the only target that has been evaluated in a T2T study.1 Meanwhile, DAPSA allows one to define all states throughout the whole course of disease, including remission and low disease activity.1 However, it should be acknowledged that the task force did not reach agreement about the use of unidimensional versus multidimensional instruments for assessing disease activity in PsA.1
“There were split opinions on the type of target to choose in PsA: only based on the musculoskeletal symptoms and, separately, skin or taking into account all aspects of the disease, including also skin, function, and quality of life in one combined measure,” said Prof. van der Heijde.2 Nevertheless, this recommendation (item 7) eventually obtained 51.6% vote of approval from the task force members, with a mean level of agreement of 7.9/10.1
The updated recommendations emerged from a systematic literature review and a meeting of a steering committee led by Prof. Josef S. Smolen, followed by a discussion of the whole task force comprising European and North American rheumatologists, dermatologists, patients, and a health professional.1 The expert panel eventually arrived at a common set of 11 updated recommendations for the three subsets of SpA: axSpA, peripheral SpA, and PsA with accompanying principles, in contrast to the additional separate recommendations for each of the SpA subsets, given that “all respective items 10 and 11 in 2012 were very similar,” the panel wrote.1
The five overarching principles in the updated recommendation are largely unchanged from the 2012 version, other than some wording changes meant to increase the clarity of message (Table 2), with emphasis placing on the concept that treatment target should be patient-based.1 The perspective of content remained similar to the one in previous version, in which the recommendations constituted a general approach to treatment rather than advising specific types of treatment.1
The updates were warmly received by the society. “The recommendations are significant in two key areas. They indicate that treat-to-target should be the standard and general approach to care of SpA and PsA. And further, they emphasize that the targets should be clinical remission or inactive disease,” said David I. Daikh, Rheumatology Division Chief at the San Francisco Veterans Affairs Medical Center, and director of the rheumatology fellowship program at University of California, San Francisco.8
While the updates strengthen the importance of a tight control strategy, concerns were raised that this might result in overtreatment.
“This principle translates to considering mild disease to be ominous and spontaneous remission to be transient. Many patients/people with or without these diseases develop back pain or rash or joint pain as coincidental, incidental, self-limited episodes that do not merit interventions carrying any important degree of risk. Will these ‘updated recommendations’ advantage the vast majority of people/patients who have little risk of severe disease?” said Nortin Hadler, emeritus professor of medicine at University of North Carolina at Chapel Hill.8
Dr. Hadler also expressed his concerns of a biased recommendation due to the general lack of compelling data in this field. “The update strengthens the 2012 recommendations, but that reflects the bias inherent in this collection of recommenders much more than the compelling nature of the published studies or the validity of the observational clinimetrics,” he said. His opinion was echoed by Dr. Daikh, who agreed that further validation would be required. “The optimal disease measures for each condition, as well as the role of multidimensional composite disease activity scores are important unanswered questions.”8
Indeed, although the 2017 update addressed several important points in the previous guideline, other items in the research agenda remained and new questions arose. The task force outlined an extensive research agenda where evidence is needed, with coverage of twelve areas in the field.1 Among them, Prof. van der Heijde highlighted several research topics that require more focus, including the role of the Health Assessment Questionnaire, validation of PsA target outcomes, and differences in outcomes with remission or low disease activity as treatment targets.5
In summary, the new T2T recommendations are useful not only in reinforcing previous framework for physicians to optimize SpA management, but also paving the way for future research to better define and refine treatment targets. It is hoped that adhering to these recommendations may significantly improve the outcomes in SpA patients.
1. Smolen JS, Schols M, Braun J, et al. Treating Axial Spondyloarthritis and Peripheral Spondyloarthritis, Especially Psoriatic Arthritis, to Target: 2017 Update of Recommendations by an International Task Force. Ann Rheum Dis 2017. doi:10.1136/annrheumdis-2017-201734.
2. Eular Congress News. European League Against Rheumatism, 2017. (Accessed August 7, 2017, at http://www.eularcongressnews.com/wp-content/uploads/2017/06/EULAR-2017-THURSDAY-lores.pdf.)
3. Smolen JS, Aletaha D, Bijlsma JW, et al. Treating Rheumatoid Arthritis to Target: Recommendations of an International Task Force. Ann Rheum Dis 2010;69:631-637.
4. Smolen JS, Braun J, Dougados M, et al. Treating Spondyloarthritis, Including Ankylosing Spondylitis and Psoriatic Arthritis, to Target: Recommendations of an International Task Force. Ann Rheum Dis 2014;73:6-16.
5. Panel Revises Spondyloarthritis Treat-to-Target Recommendations. MDedge, 2017. (Accessed August 8, 2017, at http://www.mdedge.com/rheumatologynews/article/141104/spondyloarthropathies/panel-revises-spondyloarthritis-treat-target.)
6. Coates LC, Moverley AR, McParland L, et al. Effect of Tight Control of Inflammation in Early Psoriatic Arthritis (Ticopa): A Uk Multicentre, Open-Label, Randomised Controlled Trial. Lancet 2015;386:2489-2498.
7. Che H, Etcheto A, Dernis E, et al. Evaluation of Collected Outcome Measures in Axial Spondyloarthritis in Daily-Care Rheumatology Settings: The Experience of the Rhever Network. Clin Exp Rheumatol 2015;33:851-857.
8. International Guidelines Say Use Treat-to-Target for Spa, Psa. Medscape, 2017. (Accessed August 8, 2017, at http://www.medscape.com/viewarticle/883193#vp_2.)