Inflammatory variables have been shown to be directly associated with the Patient Global Assessment (PGA) across different disease activity states in the early stages of rheumatoid arthritis (RA) and especially in autoantibody-positive individuals, according to study results published in Annals of the Rheumatic Diseases.

Researchers sought to evaluate the associations between the PGA and measures of disease activity in patients with RA relative to disease duration and autoantibody status. Although the PGA is included in disease activity indices and remission criteria in RA, its low correlation with measures of inflammation in individuals with established disease is a source of controversy regarding interpretation of the PGA as a marker of disease activity.

The study utilized data from a total of 1412 patients with RA from 3 independent cohorts: (1) a prospective cohort of 801 consecutive patients with early RA referred to the Early Arthritis Clinic of the Division of Rheumatology of the Policlinico San Matteo (PSM) in Pavia, Italy, between 2005 and 2017, who were followed longitudinally from enrollment to 24 months; (2) a cross-sectional cohort of 210 consecutive patients with established RA (>5 years) from the outpatient clinic of PSM, based on the fulfillment of at least low disease activity according to the 28-joints Disease Activity Score (DAS28) of less than 3.2; and (3) a cross-sectional cohort of 401 consecutive patients with established RA from the Department of Rheumatology of Gaetano Pini in Milan, Italy, of at least moderate disease activity (DAS28 >3.2).


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Correlations of the PGA were analyzed via Pearson coefficients and multivariable linear regression at baseline, month 6, month 12, and month 24 in the overall populations, as well as following stratification for autoantibody subgroup and remission status. These were stratified by: (1) Boolean-based remission (Tender Joint Count on 28 Joints [TJC28], Swollen Joint Count on 28 Joints [SJC28], C-reactive protein [CRP; mg/dL], and PGA, all ≤1); (2) remission missed solely because of PGA 1 (ie, PGA near remission: TJC28, SJC28, and CRP [mg/dL] ≤1; PGA <1); and (3) nonremission (ie, TJC28, SJC28, or CRP [mg/dL] >1).

Results of the study showed that in patients with early RA in nonremission, swollen joints correlated independently with the PGA, with the association becoming progressively weaker but persisting at all time points in autoantibody-positive patients (adjusted r=0.30 to 0.12). The association lost significance after month 12 among autoantibody-negative patients.

Swollen joints correlated independently with the PGA also in near remission until month 12 (adjusted r=0.18 to 0.16) among autoantibody-positive patients. There were no independent correlations of inflammatory variables observed in patients with established RA, regardless of autoantibody status and disease activity.

Limitations of the study included the fact that the data used referred to a population followed in a semitrial regimen. Therefore, the generalizability of the results needs to be confirmed in other settings as well. Additionally, different formulations and scales used for the PGA may have impacted the study results. Because such variables as fatigue, depression, and anxiety were not systematically recorded, this precluded evaluation of all possible associations of the PGA.

The study authors concluded that in patients with RA, “optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.” It is possible that optimal cut-off values of the PGA might even differ in different phases of the disease and among autoantibody subgroups.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Bugatti S, De Stefano L, D’Onofrio B, et al. Inflammatory correlates of the Patient Global Assessment of Disease Activity vary in relation to disease duration and autoantibody status in patients with rheumatoid arthritis. Ann Rheum Dis. Published online May 27, 2022. doi:10.1136/annrheumdis-2022-222436