The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.
The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University and his coauthors wrote in the March issue of Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011;70:404-13).
One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.
The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale) and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.
The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.
The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.
The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.
In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3). "The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician’s (swollen and tender joint counts) and patient’s (global health score) judgments together with laboratory data (CRP)."
The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that’s the next step – their uses in clinical practice settings are limited. The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings. "Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting." Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.
However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients. Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biologics therapy has been represented in one or more treatment arms.
The new definitions also "represent another successful ACR-EULAR collaboration," said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark. And, they added, "With ‘treat to target’ as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission."
They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice. "The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time."
The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.