Research Identifies Potentially Predictive Factors of Rheumatoid Arthritis Disease Course

Biological markers collected early in the disease course of rheumatoid arthritis could help improve patient management, researchers said.

A cohort study published in Therapeutic Advances in Musculoskeletal Disease found that lower levels of disease activity, functional disability, and alcohol consumption at baseline were linked with remission after 6 months among patients with seropositive rheumatoid arthritis (RA) taking conventional synthetic disease-modifying antirheumatic drugs (DMARDs).

The researchers hypothesized that biological markers collected within 6 months of disease onset could improve patient management and better target both existing and novel therapies.

In a study, the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) were used to measure disease activity in 267 participants with early, untreated seropositive RA every 3 months for up to 18 months. All patients were newly diagnosed with RA and naïve to DMARDs or glucocorticoid therapy. Following trial enrollment, patients began receiving DMARDs.

Based on the SDAI definition, 24.3% of participants reached 6-month remission; lower baseline SDAI and Health Assessment Questionnaire (HAQ) scores—indicating disease activity and functional disability, respectively—predicted 6-month remission (SDAI: P = .011; HAQ: P = .013).

The study helped identify 3 unique disease trajectory subpopulations, differing in disease course and risk factors. These subpopulations were defined as an inadequate responder group (6.5%), and higher and lower baseline activity responder groups (22.4% and 71.1%).

“Differential effects of functional and mental well-being, alcohol consumption, and baseline RA medication prescribing on disease activity severity were found across subpopulations,” the study authors said. “Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors.”

The researchers also found multiple baseline clinical predictors linked to disease activity severity and mixed effects of alcohol intake within these subpopulations.

Although models "indicated that alcohol consumption increased the odds of remission at 6 months compared to not consuming alcohol, they gave conflicting ordering of effect sizes across the alcohol consumption categories of 1–5 units and greater than 5 units per week," authors noted.

Of the 267 patients, 130 (48.7%), 67 (25.1%), and 70 (26.2%) enrolled in the first, second, and third recruitment periods, respectively. From there, 245 were followed up to or beyond their 6-month assessment visit and 75, 2, 60, 3, and 105 had their last assessment visit at 6, 9, 12, 15, and 18 months, respectively.

Of those recruited in the first, second, and third periods, 80.8% (105), 83.6% (56), and 92.9% (65) reached their target follow-up assessment visits of 18, 12, and 6 months, respectively.

“At 6 months, the mean (SD) DAS28-CRP and SDAI were 3.04 (1.25) and 11.37 (10.71), respectively,” the authors reported. “Based on European League Against Rheumatism (EULAR) response criterion, 110 (47.2%) patients had good response, 79 (33.9%) moderate, and 44 (18.9%) no response.”

“Regarding remission by different criteria, 97 (41.3%) patients achieved DAS28-CRP remission, 57 (24.3%) SDAI remission, and 51 (21.5%) met the American College of Rheumatology (ACR)/EULAR Boolean remission criteria reflecting increased stringency of definitions,” they added. “All 57 patients in SDAI remission were in DAS28-CRP remission. There was excellent agreement between SDAI and ACR/EULAR Boolean remissions.”

The authors concluded that the incorporation of biomarkers collected at baseline and early follow-up visits may “help patient management and better targeting of existing and novel therapies.”


Barnes M, Brockbank S, Bruce IN, et al; RA-MAP Consortium. Characterization of disease course and remission in early seropositive rheumatoid arthritis: results from the TACERA longitudinal cohort study. Ther Adv Musculoskel Dis. Published online October 21, 2021. doi:10.1177/1759720X211043977