Predictors for worse outcomes in low–disease activity RA remain tough to come by

Disease flares are common but are hard to predict in people with rheumatoid arthritis who achieve low disease activity (LDA), and these flares are “undeniably” associated with worse disease activity, quality of life, and radiographic progression, researchers report in an analysis of a prospectively observed cohort.

First author Katie Bechman, MBChB, of the academic rheumatology department at King’s College London, and her colleagues reported online in the Journal of Rheumatology that nearly one-third of patients with RA in stable LDA states, including remission, had flares during a year of follow-up in the observational prospective REMIRA study, similar to previous reports in cohort studies.

Suze777/Thinkstock

The cohort of 152 patients had 28-joint Disease Activity Scores (DAS28) less than 3.2 for at least 1 month apart, and 66% (n = 97) of the cohort fulfilled DAS28 remission criteria (DAS28 less than 2.6). The authors defined disease flare as a DAS28 increase of more than 1.2, compared with baseline, or a DAS28 increase of more than 0.6, compared with baseline, and concurrent DAS28 of 3.2 or greater. A total of 69 (35%) were taking disease-modifying antirheumatic drug monotherapy.

Nearly one-third of RA patients (30%, n = 46) with LDA states experienced a flare during 12 months of follow-up. When limiting the cohort to patients who were in remission at baseline, 25% (n = 24) had at least one flare.

Patients who had a flare experienced significantly worse clinical outcomes at 12 months than did patients in sustained remission, reflected by higher disease activity, worse functional outcomes, and higher radiographic progression scores.

For example, patients who flared had more than a threefold greater risk for erosive progression, defined as new or larger erosions over 1 year on radiographs (hazard ratio, 3.6; 95% confidence interval, 2.77-4.67; P less than .01).

Patients’ baseline values on the Health Assessment Questionnaire-Disability Index – a measure of functional activity that is reflected by difficulties in activities of daily living – proved to be a significant independent predictor of flare (HR, 1.76; 95% CI, 1.05-2.93; P = .03) in multivariate analyses.

The researchers also found that serum biomarkers were modestly correlated with DAS28 at the time of flare. DAS28 and its components significantly correlated with multibiomarker disease activity score and calprotectin at time of flare, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers.

“This might be because a flare is defined by worsening of the DAS28 composite score, and an increase in [tender joint count] and [patient’s global assessment] alone may increase the DAS28 score to a sufficient level to define a flare,” the investigators suggested.

“It is possible that a flare event is not solely the result of direct synovial inflammation but may be driven by other pathways, for example chronification of pain due to central sensitization and abnormal regulatory mechanisms. This heterogeneity may partly explain why identifying predictors of flare is challenging,” they said.

“In our study, we have shown that the occurrence of a flare is hard to predict, but undeniably associated with worse clinical outcomes at 12 months,” the researchers concluded.

They suggested that it was possible that two “distinct subtypes” of flare might exist: an “inflammatory” flare that was predominantly driven by an increase in swollen joint count and erythrocyte sedimentation rate, and a “noninflammatory” flare with a disproportionately elevated tender joint count and a high patient global assessment score.

“Differentiating these two flare types may identify potential predictors. Further research is needed to determine whether distinct flares exist and to categorize the potential predictors of each,” they added.

The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.

SOURCE: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.

Disease flares are common but are hard to predict in people with rheumatoid arthritis who achieve low disease activity (LDA), and these flares are “undeniably” associated with worse disease activity, quality of life, and radiographic progression, researchers report in an analysis of a prospectively observed cohort.

First author Katie Bechman, MBChB, of the academic rheumatology department at King’s College London, and her colleagues reported online in the Journal of Rheumatology that nearly one-third of patients with RA in stable LDA states, including remission, had flares during a year of follow-up in the observational prospective REMIRA study, similar to previous reports in cohort studies.

Suze777/Thinkstock

The cohort of 152 patients had 28-joint Disease Activity Scores (DAS28) less than 3.2 for at least 1 month apart, and 66% (n = 97) of the cohort fulfilled DAS28 remission criteria (DAS28 less than 2.6). The authors defined disease flare as a DAS28 increase of more than 1.2, compared with baseline, or a DAS28 increase of more than 0.6, compared with baseline, and concurrent DAS28 of 3.2 or greater. A total of 69 (35%) were taking disease-modifying antirheumatic drug monotherapy.

Nearly one-third of RA patients (30%, n = 46) with LDA states experienced a flare during 12 months of follow-up. When limiting the cohort to patients who were in remission at baseline, 25% (n = 24) had at least one flare.

Patients who had a flare experienced significantly worse clinical outcomes at 12 months than did patients in sustained remission, reflected by higher disease activity, worse functional outcomes, and higher radiographic progression scores.

For example, patients who flared had more than a threefold greater risk for erosive progression, defined as new or larger erosions over 1 year on radiographs (hazard ratio, 3.6; 95% confidence interval, 2.77-4.67; P less than .01).

Patients’ baseline values on the Health Assessment Questionnaire-Disability Index – a measure of functional activity that is reflected by difficulties in activities of daily living – proved to be a significant independent predictor of flare (HR, 1.76; 95% CI, 1.05-2.93; P = .03) in multivariate analyses.

The researchers also found that serum biomarkers were modestly correlated with DAS28 at the time of flare. DAS28 and its components significantly correlated with multibiomarker disease activity score and calprotectin at time of flare, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers.

“This might be because a flare is defined by worsening of the DAS28 composite score, and an increase in [tender joint count] and [patient’s global assessment] alone may increase the DAS28 score to a sufficient level to define a flare,” the investigators suggested.

“It is possible that a flare event is not solely the result of direct synovial inflammation but may be driven by other pathways, for example chronification of pain due to central sensitization and abnormal regulatory mechanisms. This heterogeneity may partly explain why identifying predictors of flare is challenging,” they said.

“In our study, we have shown that the occurrence of a flare is hard to predict, but undeniably associated with worse clinical outcomes at 12 months,” the researchers concluded.

They suggested that it was possible that two “distinct subtypes” of flare might exist: an “inflammatory” flare that was predominantly driven by an increase in swollen joint count and erythrocyte sedimentation rate, and a “noninflammatory” flare with a disproportionately elevated tender joint count and a high patient global assessment score.

“Differentiating these two flare types may identify potential predictors. Further research is needed to determine whether distinct flares exist and to categorize the potential predictors of each,” they added.

The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.

SOURCE: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.

Disease flares are common but are hard to predict in people with rheumatoid arthritis who achieve low disease activity (LDA), and these flares are “undeniably” associated with worse disease activity, quality of life, and radiographic progression, researchers report in an analysis of a prospectively observed cohort.

First author Katie Bechman, MBChB, of the academic rheumatology department at King’s College London, and her colleagues reported online in the Journal of Rheumatology that nearly one-third of patients with RA in stable LDA states, including remission, had flares during a year of follow-up in the observational prospective REMIRA study, similar to previous reports in cohort studies.

Suze777/Thinkstock

The cohort of 152 patients had 28-joint Disease Activity Scores (DAS28) less than 3.2 for at least 1 month apart, and 66% (n = 97) of the cohort fulfilled DAS28 remission criteria (DAS28 less than 2.6). The authors defined disease flare as a DAS28 increase of more than 1.2, compared with baseline, or a DAS28 increase of more than 0.6, compared with baseline, and concurrent DAS28 of 3.2 or greater. A total of 69 (35%) were taking disease-modifying antirheumatic drug monotherapy.

Nearly one-third of RA patients (30%, n = 46) with LDA states experienced a flare during 12 months of follow-up. When limiting the cohort to patients who were in remission at baseline, 25% (n = 24) had at least one flare.

Patients who had a flare experienced significantly worse clinical outcomes at 12 months than did patients in sustained remission, reflected by higher disease activity, worse functional outcomes, and higher radiographic progression scores.

For example, patients who flared had more than a threefold greater risk for erosive progression, defined as new or larger erosions over 1 year on radiographs (hazard ratio, 3.6; 95% confidence interval, 2.77-4.67; P less than .01).

Patients’ baseline values on the Health Assessment Questionnaire-Disability Index – a measure of functional activity that is reflected by difficulties in activities of daily living – proved to be a significant independent predictor of flare (HR, 1.76; 95% CI, 1.05-2.93; P = .03) in multivariate analyses.

The researchers also found that serum biomarkers were modestly correlated with DAS28 at the time of flare. DAS28 and its components significantly correlated with multibiomarker disease activity score and calprotectin at time of flare, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers.

“This might be because a flare is defined by worsening of the DAS28 composite score, and an increase in [tender joint count] and [patient’s global assessment] alone may increase the DAS28 score to a sufficient level to define a flare,” the investigators suggested.

“It is possible that a flare event is not solely the result of direct synovial inflammation but may be driven by other pathways, for example chronification of pain due to central sensitization and abnormal regulatory mechanisms. This heterogeneity may partly explain why identifying predictors of flare is challenging,” they said.

“In our study, we have shown that the occurrence of a flare is hard to predict, but undeniably associated with worse clinical outcomes at 12 months,” the researchers concluded.

They suggested that it was possible that two “distinct subtypes” of flare might exist: an “inflammatory” flare that was predominantly driven by an increase in swollen joint count and erythrocyte sedimentation rate, and a “noninflammatory” flare with a disproportionately elevated tender joint count and a high patient global assessment score.

“Differentiating these two flare types may identify potential predictors. Further research is needed to determine whether distinct flares exist and to categorize the potential predictors of each,” they added.

The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.

SOURCE: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.