Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

Abstract

Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

Serum chemerin levels: A potential biomarker of joint inflammation in women with rheumatoid arthritis

“…Rheumatoid arthritis (RA) is an inflammatory, chronic, progressive disease involving synovial joints and characterized by bone and cartilage erosions associated with a progressive decrease in joint functioning, leading to disability and impaired quality of life [1]. One of the main clinical challenges in RA, is the persistence of joint inflammation in many patients despite treatment with synthetic disease-modified antirheumatic drugs (synthetic DMARDs) or with biologic disease-modified antirheumatic drugs (biologic DMARDs) [2][3][4].…”

Demographic and Clinical Characteristics of Patients with Sustained and Switching Treatments Using Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs: A Multicenter, Observational Cross-Sectional Study for Rheumatoid Arthritis

“…Several studies focused on maintaining sustained low disease activity or remission about different drug regimens [ 16 , 33 ]. Others presented their outcomes of RA patients on biologics using the follow-up data [ 10 ]. We did not evaluate the impact of the treatment on the remission rates and the switching on the outcome of the disease, which is already well known [ 34 ].…”

“…However, there is uniform access for different treatment modalities of RA in all centers involved. Considering the cumulation of a vast majority of patients in the moderate disease activity group, it might have been more beneficial to sub-categorize patients with moderate disease activity further into low or high activity status as in the study by Genitsaridi et al [ 10 ] due to the proposed heterogeneity within this group. In a recent study analyzing data from the Rheumatology Informatics System for Effectiveness, it was reported that one- to two-thirds of patients had failed to alter their treatments even if they had moderate or high disease activity [ 37 ].…”

“…The details of current and previous medical treatment, including the name of the drugs, dosages, duration, and switching status, were obtained and recorded. Clinical information, including tender and swollen joint counts in 28 joints [6,10], patient's and physician's global visual analogue scale (VAS), VAS scores of pain and fatigue, and the Health Assessment Questionnaire (HAQ) Disability Index [13,14] were collected during the admission to the registry.…”

“…However, it has been thought that strict inclusion criteria and relatively small sample sizes in these trials prevent the generalizability of the outcomes to the clinical practice [ 3 ]. We think that investigating RA patients on bDMARDs beyond the prespecified time-points after treatment may help physicians assess the disease’s long-term outcome associated with the different disease categories [ 10 ].…”