Long-term treatment response in rheumatoid arthritis patients starting adalimumab or etanercept with or without concomitant methotrexate

To observe long-term clinical response and drug survival in a prospective two-year cohort study in rheumatoid arthritis (RA) patients starting adalimumab or etanercept treatment, with or without methotrexate (MTX), after failure of conventional DMARD therapy, including MTX. Disease activity score of 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were collected of 873 consecutive RA patients, treated with adalimumab or etanercept, prospectively at baseline, 4, 16, 28, 40, 52, 78 and 104 weeks of biological therapy. Sustained minimal disease activity (MDA), DAS28 <2.6 for at least 24 consecutive weeks, biological discontinuation, ΔHAQ and ΔDAS28 were compared between patients treated with or without concomitant MTX for etanercept and adalimumab separately. More patients treated with adalimumab and MTX (42%) achieved sustained MDA than patients without MTX (18%). The hazard ratio (HR) was 2.3 [1.4-3.9]. No significant difference was found in etanercept treatment (with MTX 33% vs. 28% without MTX), HR 1.1 [0.8-1.6]. More patients treated without MTX discontinued treatment than patients with MTX co-treatment in adalimumab (HR 2.1 [1.5-3.0]) and etanercept (HR 1.9 [1.0-3.4]). The mean decrease in DAS28 over time was higher for patients treated with MTX in adalimumab (regression coefficient (RC): 0.57, p <0.001), but was not significantly different in etanercept treatment (RC 0.05, p=0.427). No significant differences were found in ΔHAQ. Treatment discontinuation is lower in patients treated with MTX in both adalimumab and etanercept treatment. However, considering good clinical response, in contrast to etanercept, a synergetic effect of MTX is observed only in adalimumab treatmen

Effect of the Application of Trial Inclusion Criteria on the Efficacy of Adalimumab Therapy in a Rheumatoid Arthritis Cohort

Objective. To evaluate the influence of inclusion criteria used in rheumatoid arthritis (RA) trials with adalimumab on clinical outcome and response. Methods. The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospective cohort of patients with RA treated with adalimumab (AdRA cohort), thereby mimicking patient selection for a clinical trial. Clinical response and outcome in the resulting 11 projection groups were compared using the 28-joint Disease Activity Score (DAS28) and time-averaged DAS28 as outcome measures of efficacy. Results. Thirteen trials (n = 54-799) with 11 different sets of entry criteria were identified, resulting in 11 projection groups (n = 22-168). The DA528 at baseline was similar in the original trial and each projection group based on this trial (5.1-6.4, total AdRA cohort 5.1). After 28 weeks, the efficacy varied substantially among the 11 projected groups (change from baseline DAS28: -1.65 to -2.65, time-averaged DAS28 3.67-4.53). Expressed as outcome (DA528 at 28 weeks), the efficacy was much more similar for almost all projection groups (3.5-4.0) and thus appeared to be mostly independent of disease activity at baseline. Conclusion. We observed that different inclusion criteria for clinical trials can have a marked effect on the expected response, i.e., improvement from baseline. A novel finding is that final disease activity appeared much less dependent on initial disease activity. Our study suggests that for daily practice, one can assume that adalimumab treatment will on average result in a DAS28 between 3.5 and 4.0 after 28 weeks of treatment, regardless of baseline disease activity. (First Release June 15 2011; J Rheumatol 2011;38:1884-90; doi:10.3899/jrheum.101283

Muscle wasting in male TNF-α blocker naïve ankylosing spondylitis patients: a comparison of gender differences in body composition

Objective: To assess gender differences in body composition (BC) in a cohort of AS patients naïve to TNF-α blockers. Methods: Patients included fulfilled the Modified New York criteria for AS. Demographic information and disease activity measures (ASDAS and BASDAI) were reported. BC was measured by whole body DXA. Body fat percentage (BF%), fat mass index (FMI), fat free mass index (FFMI) and android/gynoid fat ratio were reported and compared between men and women and with the reference population (percentiles). Results: Seventy consecutive patients were included; 60% were men. Demographic variables were similar, except for dyslipidaemia (57.1% of men; 14.3% of women). Women had significantly more fat (BF%, FMI), and less muscle (FFMI) than men, but below the median of the reference population. Male AS patients had a markedly low FFMI (31.7th percentile) compared with the reference population. In the whole group, after multivariate analysis, an ASDAS CRP >3.5 was related to lower fat free mass content. In men, a significant relationship between having a high disease activity (ASDAS, BASDAI) and lower BF% or FMI percentile was found, but in women it was the opposite. Conclusion: Muscle wasting, measured as low FFMI compared with the reference population, was found in male TNF-α blocker naïve AS patients, especially in those with active disease. Women had higher volumes of body fat than men, but near the median of the reference population. The relationships between fat content and disease activity support the complex association between adipose tissue and inflammation

Fat mass lowers the response to tumor necrosis factor-a blockers in patients with ankylosing spondylitis

Objective. Our main objective was to assess the relationship between body composition (BC) and response to tumor necrosis factor-a (TNF-a) blocker treatment in patients with ankylosing spondylitis (AS). Our secondary objective was to evaluate the change of BC after treatment, accounting for sex and age. Methods. All included patients fulfilled the modified New York criteria for AS and were naive to TNF-a blocker. They were followed for at least 6 months after the start of etanercept or adalimumab. The Ankylosing Spondylitis Disease Activity Score containing C-reactive protein (ASDAS-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were reported. BC was assessed by whole body dual-energy X-ray absorptiometry. Body fat percentage (BF%), fat mass index (FMI), and fat free mass index (FFMI) were reported as absolute values and as percentiles. Results. Forty-one patients were included (61% men). The median followup was 14.3 months (interquartile range 8.4-19.4). After multivariate regression analysis, more fat at baseline (BF%, FMI, or FMI percentile) was significantly related with a lower chance of achieving a clinically important improvement of the ASDAS-CRP or BASDAI after treatment. The body composition did not change significantly after treatment, but there was a trend toward muscle recovery in men (FFMI change from 34.0th to 37.4th percentile). Conclusion. Higher body fat content at baseline was independently associated with a worse response to treatment with TNF-a blockers, measured by ASDAS-CRP and BASDAI change, and might contribute to the lower response rates in female patients. Also, there is a trend toward muscle mass recovery in male patients after treatment