Can Underlying Depression Artificially Inflate DAS28 Scores in RA?

Inflated DAS28 may indicate significant psychological morbidity and related non-inflammatory pain, rather than true disease activity.

Research from King’s College Hospital and the South London and Maudsley NHS Foundation Trust have found that symptoms of depression and anxiety may influence patient global assessment and tender joints in rheumatoid arthritis (RA).1

“The relationship between mental and physical health is bidirectional. Experiencing psychological distress may inflate the subjective severity of patient-reported symptoms such as pain and tenderness,” wrote Faith Matcham, MSC, from King’s College London and colleagues. “Psychological distress may [also] impact health outcomes by influencing health behaviors such as medication adherence and smoking.”

Increased psychological symptoms in RA is associated with poorer patient outcomes, including increased pain, fatigue, service usage, and increased risk of premature mortality. However, a recent systematic review has found that only 7 studies have examined the longitudinal relationships between depression and RA outcomes.2  Thus, researchers sought to study in a longitudinal manner the relationship between baseline depression and anxiety and patient global assessments of RA disease activity.

To examine the psychological factors associated with disease outcomes in RA, the researchers conducted a 1 year prospective study, recruiting patients attending a rheumatology outpatient clinic at King’s College Hospital.

High Yield Data Summary

  • Inflated DAS28 scores in the setting of tight RA disease control may be more indicative of psychological morbidity and non-inflammatory pathology

Forty six percent (109) of the 235 patients who completed the questionnaire reported having RA. Of those, only 56 had clinically verified RA and were included in the analysis (78.6% women, mean age 53.6 years, 64.8% white). The average time between baseline and follow-up was 1.1 years (SD = 0.4).

The researchers found that 1) depression and anxiety scores at baseline were not significant predictors of disease activity score 28 joints (DAS28) disease activity at 1-year follow-up after full adjustment; 2) depression and anxiety were significantly associated with the subjective components of the DAS28: swollen joint count and Patient Global Assessment; and 3) depression and anxiety were not significantly associated with the odds of reaching clinical remission at 1-year follow-up after adjusting for covariates.

These results support the researchers’ previous findings from clinical trial data showing a longitudinal relationship between baseline depression and anxiety and follow-up tender joints and patient global assessment.

While the researchers did not replicate their previous finding of an association between depression and anxiety and poorer outcomes in RA, this might be due to a lack of statistical power to predict a binary outcome.

 “The current study uses a more robust, validated method of identifying depression and anxiety, in a more heterogeneous clinical sample, with longer and more variable disease duration. This strengthens the evidence indicating a prospective relationship between depression and anxiety and poorer subjective disease outcomes in RA,” the authors wrote.

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The researchers noted that there are several possible explanations for the associations found between depression and anxiety and patient global assessment and tender joint counts.

Psychological distress is associated with worsened health behaviors such as failing to take medications as prescribed, increased smoking, or reduced physical activity, which can contribute to worsened disease outcomes. “The association between depression and anxiety and the subjective DAS28 elements would suggest that depression/anxiety impact perceptions and behaviors, rather than immune dysregulation,” the authors wrote.

Further investigation of mediators between depression/anxiety and RA are warranted. Potential targets for investigation include negative cognitions, behavioral activity, and health behaviors. 

Summary & Clinical Applicability

As measured by the DAS28, symptoms of depression and anxiety have implications for disease activity, primarily due to their influence on patient global assessment and tender joints.

This finding has implications in treatment decisions, as inflated DAS28 may point to psychological comorbidities and non-inflammatory pain, rather than bona fide RA activity, even in the presence of low levels of inflammatory disease markers.

Limitations & Disclosures

  • Sample size was small, limiting statistical power and the ability to control for relevant covariates
  • Lack of clinician-verified diagnosis of RA in majority of patients
  • Lack of sociodemographic data available. Because low socioeconomic status is associated with increased susceptibility to depression and RA, these findings may not be generalizable to the general RA population. The researchers did note, however, that King’s College Hospital cares mostly for people in South East London, which has a higher level of deprivation than the London average.
  • Lack of data available for psychopharmacotherapy and medications for RA

The authors declare that they have no competing interests.


  1. Matcham F, Ali S, Irving K, Hotopf M, Chalder T. Are depression and anxiety associated with disease activity in rheumatoid arthritis? A prospective study. BMS Musculoskelet Disord. 2016;17(155).
  2. Rathbun AM, Reed GW, Harrold LR. The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: a systematic review. Rheumatology (Oxford). 2013;52:1785– 94.