Non-Inflammatory Factors May Affect Disease Measurement and Treatment Targets in RA, Study Finds

Patients with rheumatoid arthritis (RA) can often struggle to reach treatment targets for disease management. In a recent study published in Rheumatology & Musculoskeletal Diseases, failures to meet these targets was more likely in those who began a new disease-modifying antirheumatic drug (DMARD) treatment regimen.

In the management of RA, DMARDs have provided great benefits for combatting the inflammatory processes taking place. Although these medications have helped many patients reach remission or states of low disease activity (LDA), noninflammatory pain can persist in these individuals.

Man With Finger Pain | image credit: sebra - stock.adobe.com

A patient with RA’s disease activity is often evaluated using the Disease Activity Score of 28 Joints (DAS28)—which compiles scores based on an acute phase reactant, swollen joint count (SJC), tender joint count (TJC), as well as patients’ subjective ratings of their health. As the authors of the present study note, the DAS28 is flawed, however, because of its inability to distinguish to what end these composite scores are influenced by pain-related or inflammatory factors.

“For example,” they wrote, “it has been previously demonstrated that high levels of pain-related features may prevent the DAS28 targets of remission and LDA from being reached, also in the absence of inflammatory disease activity.A strict adoption of the treat-to-target injunction of escalating treatment until targets are reached, without considering the role of non-inflammatory causes for the inability to reach treatment targets, might therefore potentially lead to overtreatment with DMARDs and to delay of interventions targeting pain management.”

To investigate this occurrence further, investigators evaluated patients with RA who were unable to achieve treatment targets despite being considered in inflammatory remission. These patients were assessed in follow-up appointments throughout the first 2 years of their disease. Researchers paid additional attention to those who were administered new DMARDs during follow-up to further examine the relationship between these new interventions and the chances of a patient accomplishing their treatment targets.

From 2011-2020, data from patients newly diagnosed with RA were collected from the Swedish Rheumatology Quality Register (SRQ). Each individual’s DAS28 and DMARD history was assessed at the time of their diagnosis and subsequently at 3, 6, 12 and 24 months. DAS28 Remission and LDA were defined as < 2.6 and ≤ 3.2, and inflammatory remission was defined as SJC (0-28) = 0 with C reactive protein (CRP) < 10 mg/L.

Data for a total of 11,141 patients were available at baseline, 7537 at the 3-month mark, 7106 at 6 months, 8590 at 12 months, and 7452 at 24 months. At the 3, 6, 12 and 24-month follow-up, 34%, 39%, 44% and 47% of those evaluated were identified as in inflammatory remission. Within this group, researchers observed that 20%, 22%, 20% and 19%, respectfully, did not achieve DAS28 Remission status. Furthermore, 8%,9%, 7% and 8%, respectfully, did not achieve DAS28 LDA.

Compared to patients in inflammatory remission who achieved their target goals, those in inflammatory remission who did not achieve DAS28 Remission had a higher likelihood of beginning a new DMARD at 6 months (rate ratio [RR] = 1.51; 95% CI, 1.25-1.91), 12 months (RR = 1.51; 95% CI, 1.22-1.86), as well as 24 months (RR = 1.47; 95% CI, 1.20-1.81), but not at 3 months. Similarly, patients in inflammatory remission who did not reach DAS28 LDA had an increased likelihood of beginning a new DMARD at 3 months (RR = 1.33; 95% CI, 1.05-1.69), 6 months (RR = 1.74; 95% CI, 1.34-2.26), 12 months (RR = 1.63; 95% CI, 1.23-2.16), as well as 24 months (RR = 1.68; 95% CI, 1.31-2.17).

By demonstrating that the achievement of patients’ treatment targets can be influenced by components outside disease activity, and that these components can factor into treatment decisions regarding new DMARD initiation, the researchers celebrated the success of their study. While their hypothesis was correct, in their concluding thoughts they mention how improvements can be made to their design by considering the potential impact of comorbidities, residual inflammation, the use of oral and intra-articular glucocorticoids, among other factors in patients’ treatment success and measurement.

Reference

Lindqvist J, Askling J, Lampa J. Register- based observational study of associations between inflammatory remission, formal treatment targets and the use of disease- modifying antirheumatic drugs among patients with early rheumatoid arthritis. RMD Open. 2023 Nov;9(4):e003111. doi: 10.1136/rmdopen-2023-003111