Swollen to Tender Joint Count Ratio: A Novel Combination of Routine Measures to Assess Pain and Treatment Response in Rheumatoid Arthritis

Pain is a hallmark symptom of rheumatoid arthritis (RA). Despite treatment with disease-modifying antirheumatic drugs (DMARDs), 71% of RA patients cite pain as a major priority (1) and approximately one-third of RA patients do not respond to DMARDs, according to the American College of Rheumatology (ACR)/European League Against Rheumatism response criteria (2). Studies report high rates of comorbid fibromyalgia in RA (3), suggesting that a large subset of RA patients “centralize” their pain. These patients have widespread pain sensitivity, which may be due to alterations in central nervous system (CNS) pain regulatory mechanisms. It has been hypothesized that abnormalities in the CNS pain regulatory mechanisms predispose RA patients to poor DMARD response because DMARDs work on peripheral inflammatory pain mechanisms rather than central pain mechanisms. In this issue of Arthritis Care & Research, Kristensen et al (4) propose that the swollen to tender joint count ratio (STR) can identify RA patients with abnormal CNS pain regulatory mechanisms and that the STR predicts response to tumor necrosis factor (TNF) inhibitors. Kristensen et al characterized the STR in 2,507 RA patients starting TNF inhibitors in the South Swedish Arthritis Group Register. They also examined the association between baseline STR and DMARD response, assessed by the ACR 20% and ACR 50% (ACR50) improvement criteria. STR was defined as the swollen joint count divided by the tender joint count, using the standard 28-joint assessment. Patients with no swollen and/or tender joints at baseline were excluded. Based on distribution plots, the STR was categorized into 3 groups: low (STR 0.5), moderate (0.5 STR 1), and high (STR 1). At baseline, 14% of patients had an STR in the low range, 47% had an STR in the moderate range, and 39% had an STR in the high range. Patients with low STRs had higher pain levels than patients with moderate or high STRs, whereas patients with moderate or high STRs had higher C-reactive protein (CRP) levels and longer disease durations. After 6 months of anti-TNF treatment, patients with moderate/ high baseline STRs (moderate STR: 39% [95% confidence interval (95% CI) 35–43%] and high STR: 40% [95% CI 36–44%]) had significantly higher ACR50 response rates compared to those with low baseline STRs (23% [95% CI 18–29%]). In a multivariable logistic regression model adjusted for sex, disease duration, baseline disease activity score in 28 joints, baseline Health Assessment Questionnaire (HAQ) score, corticosteroid use, and methotrexate treatment, patients with moderate baseline STRs were significantly more likely to achieve an ACR50 response at 6 months compared to patients with low baseline STRs (odds ratio [OR] 1.93, P 0.004). Similarly, patients with high baseline STRs were significantly more likely to achieve an ACR50 response at 6 months than patients with low baseline STRs (OR 2.82, P 0.001). Based on these data, the authors concluded that the STR is an important predictor of response to TNF inhibitors. The concept of the STR is attractive because it is easy to apply to routine clinical care. The components of the STR, the swollen and tender joint counts, are standard measures of RA disease activity, which are routinely obtained as a part of clinical assessments, and the STR ratio can be easily calculated during a clinical visit by simply dividing 2 numbers. It is particularly interesting that the association between STR and TNF response remained after adjustment for disease activity measures. These results suggest that the association between STR and TNF response was not simply an artifact of an association between inflammatory disease activity and treatment response. In fact, STR was a stronger predictor of TNF response than inflammatory measures of disease activity. CRP level was not significantly associated with TNF response, and swollen joint Dr. Lee’s work was supported by the NIH (K23-AR057578) and the Katherine Swan Ginsburg Fund. Yvonne C. Lee, MD, MMSc: Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts. Dr. Lee has received research support from Forest and owns stock in Merck, Novartis, Cubist, and Elan Corporation. Address correspondence to Yvonne C. Lee, MD, MMSc, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, 75 Francis Street, PBB-B3, Boston, MA 02115. E-mail: ylee9@partners.org. Submitted for publication June 29, 2013; accepted in revised form August 1, 2013. Arthritis Care & Research Vol. 66, No. 2, February 2014, pp 171–172 DOI 10.1002/acr.22106 © 2014, American College of Rheumatology