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Introduction: Tumor necrosis factor antagonists have revolutionized the therapeutic management of inflammatory bowel disease. Infliximab and adalimumab were the first biological agents used to induce and maintain remission in ulcerative colitis. More recently, a third tumor necrosis factor antagonist, golimumab, was approved, extending the therapeutic approach for moderate-to-severe ulcerative colitis. Areas covered: In this review, the authors review the literature on the efficacy and safety of golimumab in the context of other anti-TNF agents used in the treatment of this disease. The role of therapeutic drug monitoring in the case of loss of response to an anti-TNF agent is also discussed. Expert opinion: Golimumab is currently effective to induce and maintain remission in patients with ulcerative colitis, especially those patients who are naive for an anti-TNF agent. No large studies have evaluated the efficacy of golimumab after failure of a first-line TNF antagonist therapy. In the case of loss of response to a first anti-TNF agent, therapeutic drug monitoring is essential to determine the most suitable therapeutic option.

Background Patient registry data serves an increasing role in drug safety and comparative effectiveness research, but registry databases often do not contain confounder information measured at the same time that treatments begin. This study evaluated a set of approaches for estimating confounder values at treatment initiation using actual data from a rheumatoid arthritis (RA) registry to examine the risk of infection associated with different biologic DMARDs (bDMARDs). Methods We examined the risk of infection associated with starting a TNF inhibitor (TNFi) versus any of the other non-TNFi bDMARDs. Different confounder assessment approaches were tested. All approaches were tested in Cox proportional hazard regression models that used a propensity score (PS). The confounder of interest was the disease activity score (DAS28-CRP). The confounder assessment approaches utilized different temporal relationships between the DAS28-CRP measurement and the start of the treatments of interest. Results We included 219 subjects with RA with 269 initiations of either a TNFi or a different bDMARD or both. Among this group, 305 infections were reported and confirmed through chart review. The hazard ratio (HR) for the risk of infection associated with use of a non-TNFi bDMARD ranged from 1.17 to 3.03 using 13 different approaches; only the approach with the highest HR produced results significantly different than one, but this approach included the fewest subjects and infections. Conclusions The relative risk of infection for TNFi and other non-TNFi bDMARDs was similar using various approaches regarding which DAS28-CRP score should be used as the baseline measure in adjusted analyses. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1330-0) contains supplementary material, which is available to authorized users.

Journal Article; BACKGROUND Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus, they are treated with the first TNF antagonists in monotherapy. The aim of this study was to analyse the csDMARD and GC prescription patterns before and during treatment with the first TNF antagonist, and compare their effectiveness in three groups of patients. METHODS An observational, prospective, multicentre study in common clinical practice was designed. Treating rheumatologists recorded patient variables, including previous and concomitant csDMARDs and GCs in a database. The data were analysed using descriptive, inferential and multivariate statistics. RESULTS There were 1136 patients included; 21 % received the first TNF antagonist in monotherapy, 67 % received the first TNF antagonist plus one csDMARD, and 12 % the first TNF antagonist plus two or more csDMARDs. Most patients were female (73 %), RF+, and ACPA+, and had erosions; mean age was 53.2 (±13.0) years, and duration of disease was 9.1 (±7.6) years. They had high activity with DAS28 of 5.8 ± 1.1, and poor physical function with HAQ of 1.43 ± 0.63, and significant differences between groups in clinical variables and comorbidities; 94 % had received treatment with GCs, MTX, LFN, or SSZ at any time before the first TNF antagonist, 5 % (n = 52) had been treated with CLQ or HCLQ, and 1 % (n = 13) had received neither GCs nor csDMARDs. Before the first TNF antagonist, the drugs most commonly used were GCs (78 %), MTX (50 %), LFN (44 %), and SSZ (21 %). Concomitantly with the first TNF antagonist, 977 patients (85 %) were receiving GCs, MTX, LFN, or SSZ; 15 % (n = 173) received their first TNF antagonist without any concomitant GCs or csDMARDs, true monotherapy, and 6 % received their first TNF antagonist with GCs. The drug most commonly used at the time of first TNF antagonist initiation was MTX (58 %). All treatment groups had clinically and statistically significant improvements in DAS and HAQ scores. Effectiveness analysis (controlling for confounders) showed mean drug survival of 16.7, 20.1 and 11.7 months in each group, respectively (p

Highlights • ECL-based assays for measurement of adalimumab and adalimumab antibodies. • Performance of ECL antibody assay not significantly improved by acid dissociation. • Negative correlation between levels of antibody and free adalimumab. • Negative correlation between adalimumab level and disease activity scores., Patients treated with the TNF antagonist adalimumab develop anti-therapeutic antibodies (ATA), the prevalence of which varies depending on the assay used. Most assays are compromised due to the presence of adalimumab in the clinical samples. Our objective was to develop an antibody assay, applicable for clinical testing, which overcomes the limitation of therapeutic interference and to further determine the relationship between ATA development, adalimumab levels and disease activity in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS). Use of an electrochemiluminescence platform permitted development of fit-for-purpose immunoassays. Serum samples from patients, taken prior to and at 12 and 24 weeks of treatment, were retrospectively analysed for levels of adalimumab and ATA. Overall, the antibody prevalence was 43.6% at 12 weeks and 41% at 24 weeks of treatment. Disruption of immune complexes by acid dissociation, a strategy often adopted for this purpose, only marginally increased the antibody prevalence to 48.7% and 46% at 12 and 24 weeks respectively. We found that antibody formation was associated with decreasing levels of circulating adalimumab, but no direct effect on disease activity was evident as assessed using DAS28 for RA patients and BASDAI for PsA and AS patients. However, a negative correlation of free adalimumab trough levels with disease activity scores was observed. Data showed that adalimumab levels can serve as an indicator of ATA development which can then be confirmed by ATA testing. Monitoring of both therapeutic and antibodies should be considered during adalimumab therapy to allow clinicians to personalise treatments for maximal therapeutic outcomes.

Crohn's disease and ulcerative colitis represent the two major forms of inflammatory bowel disease (IBD). Recent research points out the role of uncontrolled intestinal inflammation in the pathogenesis of IBD. Therefore, there is a growing interest in developing novel biologic therapies targeting specific molecules of the inflammatory cascade. Among them, anti-tumor necrosis factor (anti-TNF) agents (i.e. infliximab, adalimumab, certolizumab pegol) have proved to be effective, particularly for patients with refractory IBD. These biological therapies have changed, at least partially, the clinical course and medical management of IBD. However, the administration of anti-TNF drugs has also been associated with serious side-effects, which have raised concerns on the application of these drugs in clinical practice. The goal of this review is to provide an update and analyze the pros and cons of using anti-TNF therapies in the treatment of IBD.