What Proportion of RA Patients Have Residual Pain Despite Adequate Disease Control?

A subset of patients receiving methotrexate monotherapy who achieve "good" EULAR response still have residual pain at 3 months post-treatment initiation.

A subset of patients with rheumatoid arthritis (RA) were found to have persistent pain despite improvements in Disease Activity Scores in 28 joints (DAS28) with methotrexate (MTX) therapy, suggesting components of RA pain are not mediated by inflammatory processes and may benefit from treatment other than antiinflammatory agents. These findings were recently published in Arthritis Care & Research. 

Much of the disability associated with RA relates to the pain secondary to inflammatory joint inflammation. Adequate disease control with disease-modifying antirheumatic drugs (DMARDs) has been shown to improve measures of pain, especially in early RA.  There exists, however, patients with residual pain despite early implementation of treat-to-target therapy with adequate control of systemic inflammation.  

High Yield Data Summary

  • Residual pain is common in patients with early RA even after achieving good clinical response to MTX monotherapy, with lower levels of systemic inflammation at baseline being associated with residual pain

Researchers utilized data from The Epidemiological Investigation of RA (EIRA), a case-control study analyzing data of adults with newly diagnosed RA at the population level in Sweden.  Clinical data including RA disease activity, treatments prescribed, and any disability were pulled from The Swedish Rheumatology Quality Register (SRQ) surveillance system.  

Patients with newly-diagnosed RA initiated on MTX were asked to participate in both the EIRA and SRQ, with 1 241 patients with visual analog scale (VAS) and DAS28 followup data eventually included for data analysis. Significant residual RA pain was defined by VAS pain > 20 mm.  

The European League Against Rheumatism (EULAR) response criteria, taking into account DAS28 and total joint counts 28 (TJC28),  were used to classify treatment response as “good”, “moderate”, or “no response”.  In addition, inflammatory markers including C-reactive protein (CRP) were taken at 3 months post-MTX initiation. 

Of these patients, 40% achieved EULAR good response, 38% achieved EULAR moderate response, and 23% did not achieve any response.  After 3 months of DMARD treatment with MTX, 29% of patients who had achieved EULAR good response had residual pain.  This is in comparison to the 70% of patients who achieved EULAR moderate response with residual pain at 3 months post-treatment initiation. 

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“These data show that significant pain after good clinical response is common in early RA and support the need for more intensive pain control early in the disease,” the authors stated. 

Researchers further found that increased baseline disease activity, as measured by the Health Assessment Questionnaire (HAQ), was predictive of residual pain at 3 months despite achieving EULAR good treatment response (adjusted odds ratio [OR] 2.2 95% confidence interval 1.4–3.4] per unit increase). Reduced baseline systemic inflammation, as measured by erythrocyte sedimentation rate (ESR), was also predictive of residual pain at the same point of time (adjusted OR 0.81 [95% CI 0.70–0.93] per 10-mm increase).

Summary and Clinical Applicability

A subset of patients receiving MTX monotherapy who achieve good EULAR response still have residual pain at 3 months post-treatment initiation. 

“The observational data from the present and other studies indicate that emphasis should also be laid on better strategies for treatment of concomitant pain during the course of arthritis… [and further] emphasize that the impact on disease activity and pain do not necessarily occur in parallel”, the authors concluded. 

Limitations and Disclosures 

  • Inability to control for potential confounders known to influence symptoms of pain in RA, including depression and smoking
  • Only patients receiving MTX monotherapy were included in this data analysis, limiting generalizability

Dr Klareskog has received speaking fees from Wyeth, Bristol-Myers Squibb, Merck, Sharp & Dome, AbbVie, and Roche. Dr Lampa has received speaking fees from AbbVie, Merck, Sharp & Dome, Pfizer, UCB Pharma, Novartis, and Roche.


Altawil R, Saevarsdottir S, Wedrén S, Alfredsson L, Klareskog L, Lampa J. Remaining pain in early rheumatoid arthritis patients treated with methotrexate. Arthritis Care Res (Hoboken). 2016;68(8):1061-8. doi: 10.1002/acr.22790

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