Medication-Related Hospital Readmissions Within 30 Days of Discharge:Prevalence, Preventability, Type of Medication Errors and Risk Factors

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The effects of 5-year etanercept therapy on cardiovascular risk factors in patients with psoriatic arthritis

Objective. To investigate the effects of etanercept (ETN) on lipid metabolism and other known cardiovascular disease (CVD) risk factors in patients with psoriatic arthritis (PsA). Methods. In an observational cohort of 118 consecutive patients with PsA, CVD risk factors were assessed over 5 years. Mixed-model analyses were performed to investigate the effects of ETN therapy on CVD risk factors over time. Results. Disease Activity Score in 28 joints, C-reactive protein (CRP), and erythrocyte sedimentation rate decreased during therapy with ETN. There was an increase in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol. The TC/HDLc ratio remained unaltered. The apolipoprotein B to apolipoprotein A-I (apoB/apoA-I) ratio decreased significantly. An increase in CRP was associated with an increase in the apoB/apoA-1 ratio. Conclusion. Serum lipid concentrations showed small changes over a 5-year period of ETN therapy and were inversely associated with inflammatory markers. Other CVD risk factors remained stable. The apoB/apoA-1 ratio decreased over time and an increase in disease activity was associated with an increase in this ratio. However, this modest lipid modulation cannot explain the observed beneficial CV effects of ETN, and ETN likely exerts those effects through inflammation-related mechanisms

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

Capillary blood microsampling to determine serum biopharmaceutical concentration: Mitra® microsampler vs dried blood spot

Aim: For assessment of concentrations of biopharmaceuticals, for example, therapeutic drug monitoring, dried blood sampling of capillary blood is a convenient alternative to traditional venepuncture sampling. We investigated an alternative to dried blood spot collection on filter paper: sampling capillary blood using the Mitra® microsampler. Materials and Methods: Therapeutic monoclonal antibodies were spiked in whole blood, sampled using filter paper and Mitra microsampler and concentrations measured using specific ELISAs. Results: Good recoveries of adalimumab, infliximab, ustekinumab, vedolizumab, tocilizumab, natalizumab and rituximab were found up to 1 month of storage at room temperature, averaging 95.2% for the Mitra microsampler and 92.9% for Whatman® paper. Both hemoglobin and potassium yield satisfactory estimates for the volume of the cellular fraction of blood samples in combination with the Mitra microsampler. Conclusion: We established practical protocols for the estimation of serum/plasma concentrations of therapeutic antibodies via capillary blood microsampling

Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up

Objectives To investigate the relationship between antidrug antibodies (ADA), adalimumab concentrations and clinical response in patients with psoriatic arthritis (PsA) during 52 weeks of follow-up. Methods This prospective cohort study included 103 consecutive patients with PsA. Disease Activity Score of 28 joints (DAS28), Erythrocyte Sedimentation Rate, C reactive protein and Psoriasis Area and Severity Index were assessed. Adalimumab concentrations and ADA were measured in serum trough samples, using an ELISA and a radio immunoassay, respectively. Results Adalimumab concentrations were significantly lower at 28 and 52 weeks in patients with detectable ADA compared with patients without detectable ADA (at week 28: 1.3 mg/L (IQR 0.0-3.2) versus 8.7 mg/L (IQR 5.7-11.5), p <0.001; at week 52: 0.9 mg/L (IQR 0.0-2.9) vs 9.4 mg/L (IQR 5.7-12.1), p=0.0001). DAS28 at 28 weeks (2.16 vs 2.95, p=0.023) and 52 weeks (2.19 vs 2.95, p=0.024) showed a significant difference; patients with detectable ADA had a poorer clinical outcome than patients without. Conclusions Patients with detectable ADA had lower adalimumab concentrations and a significantly poorer clinical outcome compared with patients in whom ADA were not detecte

Dried blood spots from finger prick facilitate therapeutic drug monitoring of adalimumab and anti-adalimumab in patients with inflammatory diseases

Aims: Development of a self-sampling method for therapeutic drug monitoring (TDM) of biologicals will enhance TDM implementation in routine care and pharmacokinetic knowledge. The aim of this study was to compare adalimumab and anti-adalimumab antibody (ADA) concentration measurements in dried blood spots (DBS) obtained from finger prick with measurements in serum obtained via venepuncture, from patients with rheumatic inflammatory diseases. Methods: In this cross-sectional study, 161 consecutive patients were included. For clinical validation, DBS from finger prick and serum from venepuncture were collected simultaneously and adalimumab and ADA concentration were assessed by ELISA and antigen binding test (ABT), respectively. To convert DBS eluate results to values which can be compared to serum concentrations, five different methods were investigated, using a marker protein or a volumetric approach. Results: Adalimumab and ADA concentrations obtained from the finger prick/DBS method correlated well with serum results from the same patient (correlation coefficient > 0.87). Interestingly, antibody concentrations (either adalimumab, ADA or total immunoglobulin G) in DBS from finger prick, but not albumin, were systematically lower compared to serum. Spike experiments demonstrated a quantitative recovery for all tested proteins in DBS, suggesting a slightly different protein composition of blood collected via finger prick vs. venepuncture. We established a correction factor to relate finger prick/DBS values with serum values (approximately 1.2). Conclusions: We show here for the first time that adalimumab and ADA serum concentrations can be satisfactorily estimated by measuring concentrations in DBS eluates, collected by finger prick. This method offers great opportunity to simplify TDM of adalimumab

Association between concomitant csDMARDs and clinical response to TNF inhibitors in overweight patients with axial spondyloarthritis

Abstract Background The aim of our study was to investigate the influence of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and body mass index (BMI) on circulating drug levels and clinical response to tumour necrosis factor inhibitor (TNFi) therapy in axial spondyloarthritis (axSpA) patients. Methods Prospective observational study during 1 year with 2 cohorts (Madrid and Amsterdam) including 180 axSpA patients treated with standard doses of infliximab or adalimumab. Patients were stratified by BMI, being 78 (43%) normal weight (18.5–24.9 kg/m2) and 102 (57%) overweight/obese (≥ 25.0 kg/m2). After the first year of treatment, TNFi trough levels were measured by capture ELISA. Clinical response to TNFi was defined as ∆BASDAI ≥ 2 and clinical remission as BASDAI < 2 and CRP ≤ 5 mg/L. Logistic regression models were employed to analyse the association between concomitant csDMARDs and BMI with drug levels and clinical response. Results Seventy-nine patients (44%) received concomitant csDMARDs. The administration of concomitant csDMARDs (OR 3.82; 95% CI 1.06–13.84) and being normal weight (OR 18.38; 95% CI 2.24–150.63) were independently associated with serum TNFi drug persistence. Additionally, the use of concomitant csDMARDs contributed positively to achieve clinical response (OR 7.86; 95% CI 2.39–25.78) and remission (OR 4.84; 95% CI 1.09–21.36) in overweight/obese patients, but no association was found for normal-weight patients (OR 1.10; 0.33–3.58). Conclusions The use of concomitant csDMARDs with TNFi may increase the probability of achieving clinical response in overweight/obese axSpA patients. Further research studies including larger cohorts of patients need to be done to confirm it