Abstract

BackgroundAchievement of normal physical function is an important outcome for older patients. Previous studies of younger cohorts showed that aging, comorbidities, and joint damage influenced the physical function of patients with RA who achieved clinical remission or low disease activity (LDA). We previously demonstrated that a treat-to-target (T2T) strategy for methotrexate (MTX)-naïve elderly-onset RA (EORA) was effective with an acceptable safety profile. It showed that 60.9% of 197 patients achieved HAQ Disability Index (HAQ-DI) ≤0.5 at three years by following the T2T strategy targeting LDA (1).ObjectivesWe aimed to evaluate associated factors with HAQ-DI in the T2T strategy targeting LDA for patients with EORA during three-year observational period.MethodsTreatment was adjusted to target LDA with conventional synthetic disease-modifying antirheumatic drugs (DMARDs), followed by biological DMARDs (bDMARDs) in 197 MTX-naïve EORA patients (mean age 74.9 years) with moderate-to-high disease activity. HAQ-DI was evaluated at week 0, 24, 52, 76, 104, 128, and 156. To evaluate associated factors with SDAI and HAQ-DI over the 36-month follow-up, Bayesian hierarchical logistic regression modeling was applied for 1067 periods from the 197 patients.ResultsAt baseline, the enrolled 197 patients with EORA who had normal physical function (HAQ-DI ≤0.5) in 29.4%, HAQ-DI >0.5 and <1.5 in 36.5%, and HAQ-DI ≥1.5 in 33.0%, and the mean age (standard deviation [SD]) in each group was 72.7 (5.9), 74.8 (7.3), and 75.6 (6.7), respectively. Baseline SDAI increased in the group with higher HAQ-DI. The proportions of patients with each comorbidity and estimated creatinine clearance at baseline were not significantly different across the 3 groups.In the multilevel logistic model, the association of MTX, bDMARDs, and GC use with changes in SDAI in each period was evaluated. Age, sex, and comorbidities (chronic lung disease, cardiovascular disease, history of malignancy, osteoporosis, history of serious infections, and osteoarthritis) were included as inter-individual factors. The model indicated that the use of bDMARDs was associated with a reduction of the SDAI (ΔSDAI: -9.75, SD 0.75, p<0.001), while neither MTX (ΔSDAI: -1.25, SD 1.13, p=0.270) nor GCs (ΔSDAI: -0.78, SD 0.88, p=0.372) was associated with changes in SDAI. Chronic lung diseases (ΔSDAI: 4.64, SD 1.44, p=0.001) and osteoporosis (ΔSDAI: 3.78, SD 1.46, p=0.001) at baseline were associated with the increment of SDAI.The association of age, sex, the comorbidities, and MTX, bDMARDs, and GC use with physical function in each period was evaluated by the multilevel logistic model. The model indicated that older age (ΔHAQ-DI: 0.03, SD 0.01, p <0.001), chronic lung diseases (ΔHAQ-DI: 0.15, SD 0.10, p=0.001), and osteoporosis (ΔHAQ-DI: 0.30, SD 0.10, p=0.010) at baseline were associated with the increment of HAQ-DI. When the mean SDAI during the observation period was added to the model as an inter-individual factor, the associations of HAQ-DI with the chronic lung diseases and osteoporosis at baseline were not statistically significant.ConclusionThese data indicate that bDMARDs had a central role in reducing disease activity in the T2T strategy targeting LDA in EORA patients. Chronic lung diseases and osteoporosis at baseline were associated with increase in disease activity and worsening of physical function. However, disease activity had a greater impact on physical function than the comorbidities at baseline.

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