More stringent and consistent definitions of remission are needed in rheumatoid arthritis to assess treatment success in clinical trials as well as in routine patient care, leading rheumatologists warn.
That means sticking to the American College of Rheumatology (ACR) and the EULAR jointly approved definitions and avoiding the 28-joint Disease Activity Score (DAS28) because too many patients classed as being in remission still have active disease, according to an editorial by Dr David Felson of Boston University School of Medicine, Dr Dianne Lacaille from the University of Manchester, UK, and Dr Daniel Aletaha from the Medical University of Vienna.
In 2011, the ACR and EULAR agreed that to achieve remission either a patient must have tender and swollen joint counts of ≤1, a C-reactive protein (CRP) level of ≤1 mg/dL, and a patient global assessment of arthritis activity of ≤1 (on a 0–10 scale) or meet a second definition of a score of ≤3 on the Simplified Disease Activity Index (SDAI).
This provisional position has since been independently evaluated and is now pending approval by ACR and EULAR committees, but there are concerns about ongoing use of other definitions, particularly in clinical trials, the editorial points out.
An editor’s note on the piece in the Annals of Rheumatic Diseases also warns that the agreed criteria will be more stringently enforced in studies published by the five ACR and EULAR journals in the future.
Among the concerns addressed in the editorial is the continuing use of DAS28 which among other issues is too dependent on C-reactive protein (CRP) values, making it difficult to assess newer treatments such as interleukin-6 and JAK inhibitors that directly reduce CRP.
In defence of PGA
The editorial also comes to the defence of including patient global assessment (PGA) in the ACR/EULAR definition of remission, in response to criticisms that it does not match up with current disease activity.
But they argue, in addition to the importance of including the patient perspective, there are other critical reasons to have it in the definition including that it picks up information otherwise not captured such as fatigue and pain.
It “provides a window into disease activity related to systemic inflammation not detected by tender and swollen joint counts”, the editorial notes. “Therefore, eliminating patient global assessments from [rheumatoid arthritis] trial outcomes would compromise the ability to distinguish the comparative efficacy of different treatments.”
The authors conclude: “With remission achievable in rheumatoid arthritis, making the definition of remission stringent will ensure that patients benefit from comprehensive control of their disease.
“The DAS28 should not be used to define remission because, even with the use of low thresholds, many patients whose disease is in ‘remission’ will still have a number of swollen joints and active disease.
“Defining remission without asking patients to provide any information about their disease activity—not to mention failing to collect data on any patient-reported outcomes—risks losing valuable information on treatment efficacy.”
In an editor’s note, the five journals of the ACR and EULAR state that the jointly agreed criteria are not always used in manuscripts submitted to the journals and they would take steps to enforce their use.
“There are valid and important reasons that these activities have been undertaken by ACR and EULAR, and therefore, the conclusions of the various task forces, which have been endorsed by ACR and EULAR, should be respected by investigators and study administrators,” it states.