Interval prolongation of etanercept in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a randomized controlled trial.

OBJECTIVE: The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering are scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study. METHOD: 160 patients with rheumatoid arthritis (RA), PsA, or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomized controlled trial. The intervention group doubled the dosing interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose for 6 months and doubled the dosing-interval thereafter. The primary outcome was the proportion of patients maintaining MDA at 6 month follow-up. RESULTS: At 6 months, MDA status was maintained in 47 patients (63%) in the intervention group and 56 (74%) in the control group (p = 0.15), with comparable results in all rheumatic diseases. And median etanercept concentrations decreased from 1.50 µg/mL (interquartile range 1.06- 2.65) to 0.46 µg/mL (0.28-0.92). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months. CONCLUSION: Etanercept tapering can be done without losing efficacy in RA, PsA, and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients, low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing.

Serum drug concentrations to optimize switching from adalimumab to etanercept in rheumatoid arthritis.

Objectives: Inadequate response to adalimumab can be caused by insufficient blockade of the target tumour necrosis factor (TNF) at low serum concentrations. In such cases, patients may respond to another TNF inhibitor. We investigated whether the serum adalimumab concentration is related to the efficacy of a second TNF inhibitor, etanercept, in rheumatoid arthritis (RA). Methods: Patients with RA starting etanercept treatment were prospectively observed in the Reade Rheumatology Registry. In patients previously on adalimumab, serum concentrations were determined before treatment discontinuation. According to this concentration, three subgroups were formed: < 0.5 µg/mL, 0.5-5.0 µg/mL, and ≥ 5.0 µg/mL. The European League Against Rheumatism (EULAR) good/moderate response rate after 52 weeks of etanercept was compared between the switcher subgroups and biologic-naive patients. Results: In total, 449 consecutive patients were included, of whom 69 switched from adalimumab (15%) and 380 were biologic naive (85%). EULAR good or moderate response was achieved by 74% of the biologic-naive patients and by 72%, 50%, and 52% of switchers with adalimumab concentration < 0.5 µg/mL, 0.5-5.0 µg/mL, and ≥ 5.0 µg/mL, respectively (p = 0.15). Patients with an adalimumab concentration ≥ 0.5 µg/mL were significantly less likely to achieve EULAR good/moderate response on etanercept compared to biologic-naive patients, whereas patients with a concentration < 0.5 µg/mL did not significantly differ from patients starting etanercept without prior biologic treatment. Conclusion: RA patients with an inadequate response to adalimumab, in the presence of sufficient drug concentrations, benefit less from switching to another TNF inhibitor, etanercept.

Adherence to etanercept therapy in rheumatoid arthritis patients during 3 years of follow-up.

OBJECTIVES: To determine the percentage non-adherence to etanercept in patients with rheumatoid arthritis during three years of follow-up. METHODS: During study visits in this prospective cohort study, blood samples were taken to determine serum etanercept concentrations using ELISA and patients were asked if they had missed an etanercept dose, at which date and for what reason. Non-adherence was defined as serum etanercept concentration <0.1 µg/mL and no valid reason to miss the prescribed etanercept dose. RESULTS: In total, 292 consecutive patients treated with etanercept were included. Most patients had a valid reason to miss their etanercept dose (25/37). In total 12 out of 292 patients (4.1%, 95% confidence interval 2.2-7.2) were non-adherent during the 3 year period. In a small percentage of patients (3.4%, 95% confidence interval 0.8-10.4) who failed to respond to etanercept therapy, according to their rheumatologist, this was associated with inadequate exposure to etanercept and thus non-adherence. CONCLUSION: In this study, adherence to etanercept therapy was measured using serum etanercept concentration. In most patients an absent etanercept concentration was due to a medical reason. Furthermore, the majority of patients were adherent to etanercept therapy and had adequate drug exposure. In total, only 12 out of 292 patients (4.1%) were non-adherent during 3 years of follow-up. These findings highlight that only a small minority of patients are non-adherent to etanercept treatment, especially compared to adherence rates of other drugs. However, physicians should be aware that in patients failing to respond to treatment, non-adherence is a possible cause.

Comparison of drug survival and clinical outcome in patients with ankylosing spondylitis treated with etanercept or adalimumab.

OBJECTIVE: To compare rates of drug survival and clinical response during 2 years of follow-up in ankylosing spondylitis (AS) patients treated with etanercept or adalimumab in routine care. METHOD: Biological-naïve consecutive AS patients treated with etanercept (n = 163) or adalimumab (n = 82) were followed. Treatment discontinuation was due to inefficacy, adverse events, loss to follow-up, planning a pregnancy, or uveitis. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP). Moderate disease activity was defined as an ASDAS-CRP < 2.1. RESULTS: Twenty-seven patients (32.9%) treated with adalimumab and 30 (18.4%) with etanercept discontinued treatment. Cox regression analysis demonstrated a significant difference in survival rate between discontinuation of the drug in adalimumab patients compared with etanercept patients [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.3-4.5, p = 0.005; corrected for confounding factors: HR 2.5, 95% CI 1.3-4.5, p = 0.006]. There was no significant difference at 2 years of follow-up between the adalimumab- and the etanercept-treated patients in mean ± sd ASDAS-CRP (1.9 ± 1.1 and 2.0 ± 0.9, respectively, p = 0.624), and 23 out of 34 (67.6%) compared to 71 out of 117 (60.7%) reached ASDAS-CRP moderate disease activity (odds ratio 0.738, 95% CI 0.329-1.657, p = 0.530). CONCLUSION: No significant difference was found between AS patients treated with etanercept and those treated with adalimumab in mean ASDAS-CRP and reaching ASDAS-CRP minimal disease activity at 2 year follow-up. Drug survival rate was higher in etanercept- compared to adalimumab-treated patients. However, this should be interpreted cautiously as the risk of allocation bias cannot be excluded.