BERLIN – Comprehensive feedback from patients and clinicians indicates that the American College of Rheumatology’s core set of criteria for rheumatoid arthritis may need to be expanded to include patient-centered domains such as stiffness, self-management, and participation to measure disease flare.

With no established definition for flare, the OMERACT (Outcomes Measure in Rheumatology) Rheumatoid Arthritis Flare Group developed a working framework of flare based on patient self-report of disease worsening. Next, they put the preliminary symptom domains to the test in a comparison study, the results of which Dr. Elisabeth Lie presented at the annual European Congress of Rheumatology.

"Among clinicians and patients, episodes of disease worsening or flare are a recognized aspect of the rheumatoid arthritis disease process," Dr. Lie said. "Currently there is no established definition of flare or standardized method to measure flare."

"The aim is to develop a data-driven, patient-centered, and consensus-based definition of flare in rheumatoid arthritis for use in clinical trials ... as well as in clinical practice."

Participants were asked, "Since the start of treatment in this follow-up study, has your rheumatic disease improved, remained unchanged, or deteriorated?"

When the DAS28 (Disease Assessment Score with a 28-joint count) was used, "there was a significant difference in change at 6 months for flare versus no flare based on patient reported worsening," Dr. Lie said. Effects were larger using this working definition compared with a flare definition based on treatment change or a definition using both criteria, she added.

The preliminary symptom domains discriminated well between patients with and without worsening flare in the domains of pain and stiffness, according to Dr. Lie of the department of rheumatology at Diakonhjemmet Hospital in Oslo.

"The working definition of flare based on patient-reported worsening discriminated well between patients with and without worsening in most domains, especially those related to pain and function," Dr. Lie said.

For joint pain visual analog scale scores, the standardized mean difference (SMD) between flare and no flare was 1.30. The Short Form-36 Bodily Pain questionnaire yielded a 1.24 SMD between groups. Intensity of morning stiffness was associated with a 1.17 SMD.

Dr. Lie and her colleagues assessed 1,195 patients in the NOR-DMARD register who, according to a 5-point Likert scale, reported that they initially were "much improved" or "improved" 3 months after initiating RA treatment. At 6 months, the 79 of these patients who reported that they were "worse" or "much worse" accounted for the flare group.

"Importantly, the RA flare group has developed a preliminary flare questionnaire that is currently being applied in two randomized clinical trials and three observational studies," Dr. Lie said in an interview. "This questionnaire addresses all the important domains identified as essential by patients, and data from these studies will be very important to further the process to develop a preliminary patient-reported instrument to measure RA flare."

"The involvement of patients in the early phases of this work revealed that flares are a common occurrence in patients with RA and likely represent an underrecognized aspect of the disease experience," Dr. Lie said. "Focus groups also revealed the complexity of the flare concept and the heterogeneity of clusters of symptoms that may constitute a flare."

"I think it is fair to say that rheumatologists should pay attention to patient report of flare, especially as milder flares occurring between visits to the rheumatologist may be self-managed by the patient and underreported."

The mean age of study subjects was 55 years, their mean duration of disease was 6.3 years, and 71% were female. NOR-DMARD is an ongoing, longitudinal, observational study of patients initiating DMARD (disease-modifying antirheumatic drug) therapy. Of the 1,195 participants studied, 727 were taking methotrexate, 224 received other nonbiologic DMARD agents, 229 took a tumor necrosis factor inhibitor, and 15 were taking other biologic therapy.

Patients and clinicians used Delphi exercises (a survey process in which they identified the six most relevant domains for flare from among pain, function, swollen joints, tender joints, stiffness, participation, patient global assessment, self-management, and fatigue). Some of these identified domains are featured in the RA core set (often referred to as the American College of Rheumatology core set), but others – like stiffness, self-management, and participation – are not.

Dr. Lie explained how the investigators performed an additional analysis, defining flare by change in treatment, such as a step-up of DMARD or systemic corticosteroid therapy. This yielded 162 flare patients, only 35 of whom also were identified using their patient-centered working definition. The implication is that a flare definition based on patient report of disease worsening is truly distinct and warrants further study.

The research is ongoing. A meeting attendee suggested that Dr. Lie consider assessment of concomitant osteoarthritis in the future as well, to avoid any contribution to assessment of rheumatoid arthritis flare in the study. Further results of this study are in press in Annals of the Rheumatic Diseases.

Dr. Lie did not have any relevant financial disclosures.

RA Patient Feedback Suggests Criteria Fall Short