Predicting Flare in DMARD Treated RA Patients in Remission
Objectives The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes.
Methods RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy.
Results 26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission.
Conclusion The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.
European League Against Rheumatism (EULAR) recommendations state that remission is the goal of therapy for patients with rheumatoid arthritis (RA) and with modern therapeutic strategies this target disease state can be achieved more frequently. Remission has been described as a 'state of absent disease activity' and is the antithesis of flare which is a 'substantial increase in disease activity.'
Studies have compared patients in sustained remission with those with continued disease activity and in different disease activity states.7 High disease activity has been associated with worse functional and radiographic outcomes when compared with remission or low disease activity.
Once patients are in remission, the duration of this state is important. Patients with just short-term remission are more likely to experience radiographic structural progression compared with those achieving longer term remission. Therefore, a more appropriate target disease state should be sustained remission (the absence of disease activity and flare over the longest possible period of time). This may be more difficult to achieve as data suggest that approximately half of RA patients in remission may experience a disease flare within 24 months. Flare has been shown to be associated with more radiographic progression when compared with patients in sustained remission. Once remission is achieved, the clinician needs to be confident that the patient will maintain this state in order to ensure the best possible outcomes. Predictors of sustained tumour necrosis factor inhibitor free remission have also been published, for example, short symptom duration prior to commencing therapy; however, predictors of disease flare have not been described.
The American College of Rheumatology (ACR) and the EULAR have published criteria for remission. However, these criteria were not evaluated as to their ability to predict flare of disease.
Studies have previously demonstrated that ultrasound detected power Doppler (PD) activity (implying active synovial inflammation) may be present in a proportion of patients in clinical remission and this can be used to accurately predict subsequent radiographic structural progression. It may be hypothesised that such continued subclinical inflammation despite apparent remission as determined by traditional criteria may trigger a subsequent disease flare.
This study aimed to determine the clinical, functional and imaging factors associated with disease flare and sustained remission in a cohort of disease-modifying antirheumatic drug (DMARD) treated RA patients in clinical remission. In addition, we aimed to determine the impact of disease flare versus sustained remission on long-term, clinical, functional, quality of life and radiographic outcomes.
Abstract and Introduction
Abstract
Objectives The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes.
Methods RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy.
Results 26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission.
Conclusion The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.
Introduction
European League Against Rheumatism (EULAR) recommendations state that remission is the goal of therapy for patients with rheumatoid arthritis (RA) and with modern therapeutic strategies this target disease state can be achieved more frequently. Remission has been described as a 'state of absent disease activity' and is the antithesis of flare which is a 'substantial increase in disease activity.'
Studies have compared patients in sustained remission with those with continued disease activity and in different disease activity states.7 High disease activity has been associated with worse functional and radiographic outcomes when compared with remission or low disease activity.
Once patients are in remission, the duration of this state is important. Patients with just short-term remission are more likely to experience radiographic structural progression compared with those achieving longer term remission. Therefore, a more appropriate target disease state should be sustained remission (the absence of disease activity and flare over the longest possible period of time). This may be more difficult to achieve as data suggest that approximately half of RA patients in remission may experience a disease flare within 24 months. Flare has been shown to be associated with more radiographic progression when compared with patients in sustained remission. Once remission is achieved, the clinician needs to be confident that the patient will maintain this state in order to ensure the best possible outcomes. Predictors of sustained tumour necrosis factor inhibitor free remission have also been published, for example, short symptom duration prior to commencing therapy; however, predictors of disease flare have not been described.
The American College of Rheumatology (ACR) and the EULAR have published criteria for remission. However, these criteria were not evaluated as to their ability to predict flare of disease.
Studies have previously demonstrated that ultrasound detected power Doppler (PD) activity (implying active synovial inflammation) may be present in a proportion of patients in clinical remission and this can be used to accurately predict subsequent radiographic structural progression. It may be hypothesised that such continued subclinical inflammation despite apparent remission as determined by traditional criteria may trigger a subsequent disease flare.
This study aimed to determine the clinical, functional and imaging factors associated with disease flare and sustained remission in a cohort of disease-modifying antirheumatic drug (DMARD) treated RA patients in clinical remission. In addition, we aimed to determine the impact of disease flare versus sustained remission on long-term, clinical, functional, quality of life and radiographic outcomes.
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