Tools for monitoring remission in rheumatoid arthritis: any will do, let's just pick one and start measuring

Rheumatoid arthritis treatment has seen major changes in the last decade, one of which is the concept of treating to target. Various composite outcome measures have been developed, and the latest is the new American College of Rheumatology/European League Against Rheumatism remission criteria. Zhang and colleagues test the predictive validity of the new criteria in an observational cohort and show that they work as well as other definitions of remission. Our main challenge remains getting rheumatologists to use one of the outcome measures rather than developing new measures that are basically no different from already available measures in predicting functional and radiographic changes, the two most important long-term outcomes of rheumatoid arthritis.


In a previous issue of Arthritis Research & Th erapy,
Zhang and colleagues test the predictive validity of the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria in an observational study, the French ESPOIR cohort [1]. Patients with early rheumatoid arthritis (RA) from 14 regions across France have been included in the ESPOIR cohort since 2002, and return to the clinic for follow-up every 6 months during the fi rst 2 years and every year afterwards. For this study, a total of 641 patients fulfi lling the 2010 ACR/EULAR classifi cation criteria for RA were included.
Likelihood ratios (LR) are considered to provide a better understanding of how well these candidate defi nitions performed. In this regard, the LR for each candidate defi nition was calculated by comparing the proportion of patients having a good outcome (for both radiographic damage and physical function over the interval of 12 to 24 months after they fi rst reached remission) and whose RA was in remission with the proportion of patients having a good outcome whose RA was not in remission. Th e Boolean defi nitions with the highest LRs (2.6) for good outcomes were those that had at least fi ve measures -tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP), patient global assessment, and physician global assessment or patient pain -while the ACR/EULAR-recommended four-item remission defi nition performed very similarly (LR = 2.4). With regard to index-based defi nitions, the ACR/ EULAR-recommended Simplifi ed Disease Activity Index (SDAI) ≤3.3 performed best among the others (28-joint Disease Activity Score (DAS28) <2.6 and <2.0). In terms of defi nitions for clinical practice, which do not need CRP measurem ents, the remission defi nition of the Clinical Disease Activity Index (CDAI) that had four measures (TJC, SJC, patient global assessment, and physician global assessment) performed better (LR = 2.3) compared with those recommended by the ACR/EULAR (28-joint TJC, 28-joint SJC, patient global assessment ≤1 and CDAI ≤2.8) with LR = 2.0.
Overall, predictive validity analysis of the dataset obtained from the observational ESPOIR study shows us that the new RA remission defi nitions perform as comparably in observational studies as in clinical trials, while the LRs for several candidate defi nitions found in this cohort were a bit lower compared with those found in clinical trial datasets.
Th e last decade witnessed revolutionary developments in RA treatment with the advent of targeted biologic therapies and the use of a tightly controlled treatment approach, which have fostered improved outcomes [2]. True remission has thus now become a reality for some of our patients. Various composite disease activity indices

Abstract
Rheumatoid arthritis treatment has seen major changes in the last decade, one of which is the concept of treating to target. Various composite outcome measures have been developed, and the latest is the new American College of Rheumatology/European League Against Rheumatism remission criteria. Zhang and colleagues test the predictive validity of the new criteria in an observational cohort and show that they work as well as other defi nitions of remission. Our main challenge remains getting rheumatologists to use one of the outcome measures rather than developing new measures that are basically no diff erent from already available measures in predicting functional and radiographic changes, the two most important longterm outcomes of rheumatoid arthritis.

© 2010 BioMed Central Ltd
Tools for monitoring remission in rheumatoid arthritis: any will do, let's just pick one and start measuring  [3]. Th e committee proposed two defi ni tions of remission: an index-based score (defi ning remis sion as SDAI score ≤3.3); and a Boolean-based defi nition, which was developed using datasets from four clinical trials. However, as also stated in the original report, this needed to be validated in observational cohorts, which is a requirement to recommend their use in clinical practice [3].
Before we decide on which defi nition/measure to use in routine clinical care, it is important to know how the new ACR/EULAR remission criteria were developed. Th e ACR has focused on the need for assessing disease activity, with continued monitoring in the last two recom mendations it published [4,5]. Th ese suggest that the DAS28, SDAI, CDAI and RAPID3 are virtually identical and interchangeable for use in routine clinical care. However, there has been concern for some time now that it was possible to achieve DAS28 remission (score <2.6) but still have several swollen and tender joints [2]. To develop a more stringent remission defi nition, the ACR/EULAR committee therefore decided that functional outcome and radiographic damage should be used to validate candidate remission defi nitions because the chosen new remission defi nition should predict future good functional outcomes and an absence of radiographic damage progression. Th ey then, as stated in the manuscript, '… by consensus … agreed that any defi nition should include, as a minimum, tender and swollen joint counts and levels of an acute phase reactant' [3]. Ten diff erent combinations of the ACR core dataset measures, always including the SJC, TJC and CRP, were then tested in cohorts of patients.
Th e fi rst issue that arises from this testing is that if this was an exercise in trying to fi nd a better, more stringent defi nition of remission, why were all possible combinations of the ACR dataset measures not tested? Zhang and colleagues' paper in a previous issue of Arthritis Research & Th erapy suggests that there may have been better defi nitions to consider. Why is there a need to limit the options only to those combinations that have the SJC, TJC and CRP as part of the defi nition? Why not let the data speak for themselves?
We think part of the problem is that most physicians believe that physician-driven measures are more objective compared with the so-called subjective patient measures. Yet data suggest that patient-driven measures are actually more accurate in demonstrating what is going on with the patients earlier and are less susceptible to placebo eff ects [6,7]. Hence, asking a patient how they are doing and documenting their response may be more objective and a true refl ection of how they are doing compared with asking a physician to perform a joint count and base their decisions on that. In addition, data suggest that, regardless of the defi nition of remission used -including the Boolean ACR/EULAR defi nitionfunctional outcomes and radiographic progression are similar in groups of patients [8,9]. Our own data show that remission rates as measured by RAPID3, a patientonly composite index, and the Boolean ACR/EULAR defi nition capture virtually the same patients and that there does not seem to be an advantage to the new defi nition over what has already been in use [10].
Th e other, more critical, issue is that if physicians do not use a measure, it really does not matter how good that measure is. Joint examination is of course part of the clinical encounter with a rheumatologist, but actual 28-joint counts or other versions of joint counts are not performed frequently in routine clinical care and CRP is not always available at the time of the visit [11]. Measures that include these components are therefore going to be hard to implement, turning into a road block to 'treat to target' , whereas a patient questionnaire as part of the structure of medical care is easy to implement, does not take extra time from the physician and seems to be equivalent to any other measure [12].
In conclusion, we believe that we already have enough measures that work both in clinical trials and in routine clinical care. Why try to add more measures when our eff orts need to be focused on educating physicians how to use them and get them started on the road to treating to target? It may be worth remembering Benjamin Franklin when he said 'Lose no time; be always employed in something useful; cut off all unnecessary actions' before the ACR and the EULAR next decide to work on a joint project.