Influence of age on the occurrence of adverse events in rheumatic patients at the onset of biological treatment: data from the BIOBADASER III register.

OBJECTIVES: To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). METHODS: All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. RESULTS: 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. CONCLUSION: Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.

Factors associated with long-term retention of treatment with golimumab in a real-world setting: an analysis of the Spanish BIOBADASER registry.

The retention rate of a biological drug (percentage of patients remaining on treatment over time) provides an index of a drug's overall effectiveness. The golimumab retention rate as first-line biological therapy was high in clinical trial extensions lasting 5 years. Real-world studies also indicate good retention rates but have been of shorter duration. The probability of retention with golimumab treatment was assessed, as any line of anti-tumor necrosis factor-alpha therapy, for up to 5 years in patients with rheumatoid arthritis (RA), axial spondyloarthritis (SpA) or psoriatic arthritis (PsA), associated factors were analyzed. A retrospective database analysis of the Spanish registry of patients with rheumatic disorders receiving biological drugs (BIOBADASER) was performed. Among 353 patients, 29.8% had RA, 41.6% SpA and 28.6% PsA. Golimumab was the first biological drug in 40.1% of patients, second in 30.1% and third/later in 29.8%. The overall probability of retention of golimumab at years 1, 2, 3, 4 and 5 was 85.9% (95% confidence interval 81.4-89.5%), 73.7% (67.1-79.1%), 68.5% (60.5-75.1%), 60.6% (50.2-69.5%) and 57.1% (44.9-67.5%), respectively. Retention was similar across indications (p = 0.070) but was greater when golimumab was used as the first biological agent compared with later therapy lines (p < 0.001). Factors associated with higher retention of golimumab treatment (Cox regression) were use as a first-line biological and concomitant methotrexate treatment; corticosteroid need was associated with lower retention. The long-term probability of golimumab retention was high in this real-world study of patients with rheumatic diseases, especially when used as the first biological drug.

Circulating microRNAs as potential biomarkers of disease activity and structural damage in ankylosing spondylitis patients.

Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of microRNA (miR)-146a-5p, miR-125a-5p, miR-151a-3p and miR-22-3p, and lower expression of miR-150-5p, and miR-451a were found in AS versus healthy donors. Interestingly, higher miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p and miR-451a expression was also observed in AS than psoriatic arthritis patients. The areas under the curve, generated to assess the accuracy of microRNAs as diagnostic biomarkers for AS, ranged from 0.614 to 0.781; the six-microRNA signature reached 0.957. Bioinformatics analysis revealed that microRNAs targeted inflammatory and bone remodeling genes, underlying their potential role in this pathology. Indeed, additional studies revealed an association between these six microRNAs and potential target proteins related to AS pathophysiology. Furthermore, miR-146a-5p, miR-125a-5p and miR-22-3p expression was increased in active versus non-active patients. Moreover, miR-125a-5p, miR-151a-3p, miR-150-5p and miR-451a expression was related to the presence of syndesmophytes in AS patients. Overall, this study identified a six-plasma microRNA signature that could be attractive candidates as non-invasive biomarkers for the AS diagnosis, and may help to elucidate the disease pathogenesis.

Optimization of biological therapy in rheumatoid arthritis patients: outcomes from the CREATE registry after 2 years of follow-up.

The current strategy for managing rheumatoid arthritis (RA) focuses on achieving clinical remission. Once remission is achieved and sustained over time, the most efficient strategy is dose optimization. This work describes the results of dose optimization after 2 years of follow-up in patients with RA treated with biological therapy and identifies predictive variables of response. Cohort: patients from the CREATE registry who, as of 1 November 2013, had been in clinical remission (DAS28 ≤2.6) for at least 6 months. INTERVENTION: Dose optimization was 20-50% of the standard dose. Outcome measurement were effectiveness (percentage of patients who continued to meet criteria for clinical remission) and efficiency (dose reduction and mean savings). Sixty-eight patients with RA were optimized, with initial mean DAS28 of 2.2 ± 0.7. After 2 years of follow-up, the mean DAS28 was 2.4 ± 0.7, a non-statistically significant difference. Twenty-eight patients (41.2%) continued in clinical remission with dose optimization after 2 years. Mean survival time was 14.2 months (95% CI 12.0-16.5). Of the 40 patients who needed to return to a standard dose, 57.5% managed to achieve remission again at 2 years. Mean dose reduction at 2 years was 21.17%, reaching a mean saving of €5576 ± 5099 per patient. In actual clinical practice, over 40% of patients with established RA who had been in sustained clinical remission managed to continue in remission 2 years after receiving optimized doses. The savings achieved was about 21% of the actual direct health costs for patients in the CREATE registry.

Disease Activity As a Major Determinant of Quality of Life and Physical Function in Patients With Early Axial Spondyloarthritis.

OBJECTIVE: To describe health-related quality of life (HRQOL) and physical function in patients with early axial spondyloarthritis (SpA) and to assess their associations with disease activity and radiographic damage. METHODS: This was a cross-sectional study drawing upon baseline data of axial SpA patients (Assessment of SpondyloArthritis international Society criteria) from the ESPERANZA cohort. Linear regression analyses were used to evaluate the associations between disease activity and radiographic damage (spine and sacroiliac joints) with HRQOL, physical function, and spinal mobility. RESULTS: In total, 259 patients were included. The mean ± SD age was 32.2 ± 6.9 years, disease duration was 13.3 ± 6.8 months, Ankylosing Spondylitis Quality of Life score was 5.9 ± 4.8, Bath Ankylosing Spondylitis Functional Index score was 2.4 ± 2.3, Bath Ankylosing Spondylitis Metrology Index score was 1.4 ± 1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was 3.8 ± 2.3, C-reactive protein (CRP) level was 9.7 ± 13.2 mg/liter, and Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s) score was 1.7 ± 1.6. HRQOL was mainly associated with disease activity on univariate analysis (ß values for BASDAI 0.646, patient global visual analog scale [VAS] 0.641, night back pain VAS 0.598, physician VAS 0.560, and CRP level 0.275; P < 0.01 for all), whereas the association with radiographic damage was weaker (standardized ß for BASRI-s 0.142; P < 0.05). On multivariate models, HRQOL only remained significantly associated with disease activity (standardized ß for BASDAI 0.330; P < 0.01, and physician VAS 0.205 and night back pain VAS 0.210; P = 0.01). Similarly, physical function was associated with disease activity and radiographic damage on univariate analysis, but only with disease activity (BASDAI ß 0.466; P < 0.01) on multivariate analysis. However, spinal mobility was associated with radiographic damage in both univariate and multivariate analyses. CONCLUSION: Patients with axial SpA already have impaired quality of life and physical function, albeit mildly, at the beginning of their disease course. Both outcomes are mainly associated with disease activity in these patients.