anti-TNF Treatment In Patients Research Articles

Endothelial dysfunction and risk factors for atherosclerosis in psoriatic arthritis: overview and comparison with rheumatoid arthritis.

Endothelial dysfunction (ED) is defined as an impairment in the vasodilatory, anti-thrombotic, and anti-inflammatory properties of the cells that make up the lining of blood vessels. ED is considered a key step in the development of atherosclerotic cardiovascular disease. The association between ED and systemic inflammatory diseases is well established. However, the prevalence and clinical significance of ED in psoriatic arthritis (PsA) have been investigated to a lesser extent. This review aims to explore the link between ED and PsA, including ED in macro- and microcirculation, as well as risk factors for its occurrence in PsA and its relationship with atherosclerosis in PsA. Furthermore, the ED in PsA was compared with that of rheumatoid arthritis (RA). Regarding ED in the microcirculation, the coronary flow reserve was found to be significantly reduced in individuals with PsA. The relationship between PsA and macrovascular ED is more pronounced, along with more advanced atherosclerosis detected in patients with PsA. These results are consistent with those obtained in RA studies. On the other hand, arterial stiffness and signs of vascular remodeling were found more frequently in RA than in PsA, with the potential role of efficient anti-TNF treatment in patients with PsA and psoriasis explaining this finding. The impact of ED on cardiovascular diseases and the burden of this risk caused independently by PsA have not yet been precisely established, however, this group of patients requires special attention with regard to cardiovascular events.

Decreased TMIGD1 aggravates colitis and intestinal barrier dysfunction via the BANF1-NF-κB pathway in Crohn’s disease

BackgroundDisrupted intestinal epithelial barrier is one of the major causes of Crohn’s disease (CD). Novel molecular targets for intestinal epithelial barrier are essential to treatment of CD. Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is an adhesion molecule that regulates cell adhesion, migration, and enterocyte differentiation. However, the function and mechanism of TMIGD1 in CD and intestinal epithelial barrier has rarely been studied. Furthermore, the association between TMIGD1 and the clinical features of CD remains unclear.MethodsTranscriptome analysis on colonic mucosa from CD patients and healthy individuals were performed to identify dysregulated genes. Multi-omics integration of the 1000IBD cohort including genomics, transcriptomics of intestinal biopsies, and serum proteomics identified the association between genes and characteristics of CD. Inflammation was assessed by cytokine production in cell lines, organoids and intestinal-specific Tmigd1 knockout (Tmigd1INT-KO) mice. Epithelial barrier integrity was evaluated by trans-epithelium electrical resistance (TEER), paracellular permeability, and apical junction complex (AJC) expression. Co-immunoprecipitation, GST pull-down assays, mass spectrometry, proteomics, and transcriptome analysis were used to explore downstream mechanisms.ResultsMulti-omics integration suggested that TMIGD1 was negatively associated with inflammatory characteristics of CD. TMIGD1 was downregulated in inflamed intestinal mucosa of patients with CD and mice colitis models. Tmigd1INT-KO mice were more susceptible to chemically induced colitis. In epithelial cell lines and colonic organoids, TMIGD1 knockdown caused impaired intestinal barrier integrity evidenced by increased paracellular permeability and reduced TEER and AJC expression. TMIGD1 knockdown in intestinal epithelial cells also induced pro-inflammatory cytokine production. Mechanistically, TMIGD1 directly interacted with cytoplasmic BAF nuclear assembly factor 1 (BANF1) to inhibit NF-κB activation. Exogenous expression of TMIGD1 and BANF1 restored intestinal barrier function and inhibited inflammation in vitro and in vivo. TMIGD1 expression predicted response to anti-TNF treatment in patients with CD.ConclusionsOur study demonstrated that TMIGD1 maintained intestinal barrier integrity and inactivated inflammation, and was therefore a potential therapeutic target for CD.

Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease.

Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn's disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach.

Pharmacogenetic Analysis of the MIR146A rs2910164 and MIR155 rs767649 Polymorphisms and Response to Anti-TNF Treatment in Patients with Crohn's Disease and Psoriasis.

The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn's disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the MIR146A rs2910164 and MIR155 rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the MIR146A rs2910164, while Tsp45I was employed for the MIR155 rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected p value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.

DOP88 Understanding the molecular mechanisms of anti-TNF treatment failure: Whole blood DNA methylation changes associated with primary non-response to anti-TNF treatment in patients with Crohn’s disease

Abstract Background Anti-TNF treatment failure in patients with IBD is common and frequently related to low drug concentrations. DNA methylation sites from whole blood have been identified as effective biomarkers predicting treatment response to methotrexate and etanercept in patients with rheumatoid arthritis. We sought to define differences in DNA methylation associated with primary non-response (PNR) to anti-TNF treatment in patients with Crohn’s disease. Methods The Personalised Anti-TNF Therapy in Crohn’s disease (PANTS) study is a prospective UK-wide study investigating anti-TNF treatment failure in patients with active luminal Crohn’s disease. DNA methylation from whole blood was assessed using the Illumina EPIC Beadchip at baseline, weeks 14, 30 and 52. We compared DNA methylation profiles in a subset of adalimumab- and infliximab-treated patients who experienced PNR at week 14 and were not in remission at week 54 (infliximab = 99, adalimumab = 94) with patients who responded at week 14 and were in remission at week 54 (infliximab = 99, adalimumab = 93). Low anti-TNF drug concentration was defined as an infliximab level <3mg/L and adalimumab level <5mg/L. Epigenome-wide association (EWAS) analysis was performed using linear mixed models, where p values < 9 x 10-8 were considered significant. Because we observed significant changes in CD4 and CD8 T cells, B cells, NK cells, monocytes and granulocytes following anti-TNF treatment we adjusted our models for derived cell proportions (Figure 1). Results Overall, between baseline and week 14, we observed 4999 differentially methylated probes (DMPs) annotated to 2376 genes. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses (Figure 2). EWAS analysis at baseline identified 48 DMPs annotated to 36 genes associated with PNR (Figure 3). The majority of DMPs (40/48) were hypermethylated (p < 0.001): of those annotated to genes, 25 were located in the gene body, 5 in the 5’ untranslated regions (UTR), 4 in transcription start sites and the remaining in 3’UTR. When EWAS analysis at baseline was stratified by anti-TNF drug concentration, 27 DMPs annotated to 17 genes were associated with PNR and low drug concentration. Of these, 11 DMPs were independently associated with low anti-TNF drug concentration at week 14 (Figure 4). We did not identify any DMPs associated with PNR with adequate drug concentration. Conclusion Our data suggests that baseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14.

Cardiovascular risk assessment after anti-TNF treatment in patients with rheumatoid arthritis and ankylosing spondylitis with Strain Echocardiography

Cardiovascular risk assessment after anti-TNF treatment in patients with rheumatoid arthritis and ankylosing spondylitis with Strain Echocardiography

P475 Real world data on treatment success and drug persistence in anti-TNF therapy for ulcerative colitis

Abstract Background The efficacy and safety of anti-TNF treatment for ulcerative colitis (UC) have been well documented in clinical trials. More data are required to increase knowledge on treatment success in a real world setting. This study reports real world data on treatment success, drug persistence and safety of anti-TNF treatment in patients with UC. Methods Patients with UC starting anti-TNF treatment with infliximab (IFX) or adalimumab (ADA) between January 2014 and December 2019 at Oslo University Hospital in Norway were included in a retrospective review of medical records. Eligible patients were biologically naïve adults (≥18 years) with no history of UC-related surgery. Follow-up was 12 months. Drug persistence was defined as the proportion of patients still receiving first-line anti-TNF treatment without addition of a second biologic agent. Remission was defined as i) clinical remission (six-point Mayo Score <2), ii) biochemical remission (fecal calprotectin <250 and CRP <5) or iii) a combination of the two. Treatment success was defined as drug persistence and remission. Serious adverse events (SAEs) were defined according to Good Clinical Practice guidelines. Results In total, 116 patients were included (mean age 35.5 ±13.9 years (SD), 58% male), of which 95 received IFX treatment and 21 ADA. Drug persistence was 74%. Treatment success by different definitions of remission and remission rates for drug persistent patients according to these definitions are reported in the table. SAEs were recorded on 18 occasions (four immediate infusion reactions, two colectomies, five infections and seven other events). Conclusion Treatment success by the strictest definition of remission was 40%. Of drug persistent patients, 44% were not in remission when applying the same definition. Whether these results reflect inadequacies in definitions of remission, a tendency for clinicians to let other variables guide treatment or a delay in drug switching warrants further investigation.

A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease.

Crohn's disease is a chronic inflammatory intestinal disease that is frequently accompanied by aberrant healing and stricturing complications. Crosstalk between activated myeloid and stromal cells is critical in the pathogenicity of Crohn's disease1,2, and increases in intravasating monocytes are correlated with a lack of response to anti-TNF treatment3. The risk alleles with the highest effect on Crohn's disease are loss-of-function mutations in NOD24,5, which increase the risk of stricturing6. However, the mechanisms that underlie pathogenicity driven by NOD2 mutations and the pathways that might rescue a lack of response to anti-TNF treatment remain largely uncharacterized. Here we use direct ex vivo analyses of patients who carry risk alleles of NOD2 to show that loss of NOD2 leads to dysregulated homeostasis of activated fibroblasts and macrophages. CD14+ peripheral blood mononuclear cells from carriers of NOD2 risk alleles produce cells that express high levels of collagen, and elevation of conserved signatures is observed in nod2-deficient zebrafish models of intestinal injury. The enrichment of STAT3 regulation and gp130 ligands in activated fibroblasts and macrophages suggested that gp130 blockade might rescue the activated program in NOD2-deficient cells. We show that post-treatment induction of the STAT3 pathway is correlated with a lack of response to anti-TNF treatment in patients, and demonstrate in vivo in zebrafish the amelioration of the activated myeloid-stromal niche using the specific gp130 inhibitor bazedoxifene. Our results provide insights into NOD2-driven fibrosis in Crohn's disease, and suggest that gp130 blockade may benefit some patients with Crohn's disease-potentially as a complement to anti-TNF therapy.

Evaluation of Changes in Gut Microbiota in Patients with Crohn's Disease after Anti-Tnfα Treatment: Prospective Multicenter Observational Study.

Background: Crohn’s disease is believed to result from the interaction between genetic susceptibility, environmental factors and gut microbiota, leading to an aberrant immune response. The objectives of this study are to evaluate the qualitative and quantitative changes in the microbiota of patients with Crohn’s disease after six months of anti-tumor-necrosis factor (anti-TNFα) (infliximab or adalimumab) treatment and to determine whether these changes lead to the recovery of normal microbiota when compared to a control group of healthy subjects. In addition, we will evaluate the potential role of the Faecalibacterium prausnitzii/Escherichia coli and Faecalibacterium prausnitzii/Clostridium coccoides ratios as indicators of therapeutic response to anti-TNFα drugs. Methods/Design: This prospective multicenter observational study will comprise a total of 88 subjects: 44 patients with Crohn’s disease scheduled to start anti-TNFα treatment as described in the drug specifications to control the disease and 44 healthy individuals who share the same lifestyle and eating habits. The presence of inflammatory activity will be determined by the Harvey-Bradshaw index, analytical parameters in blood, including C-reactive protein, and fecal calprotectin levels at commencement of the study, at three months and at six months, allowing the classification of patients into responders and non-responders. Microbiota composition and the quantitative relationship between Faecalibacterium prausnitzii and Escherichia coli and between Faecalibacterium prausnitzii and Clostridium coccoides group as indicators of dysbiosis will be studied at inclusion and six months after initiation of treatment using ultra sequencing with Illumina technology and comparative bioinformatics analysis for the former relationship, and digital droplet PCR using stool samples for the latter. Upon inclusion, patients will complete a survey of dietary intake for the three days prior to stool collection, which will be repeated six months later in a second collection to minimize dietary bias. Discussion: In this study, massive sequencing, a reliable new tool, will be applied to identify early biomarkers of response to anti-TNF treatment in patients with Crohn’s disease to improve clinical management of these patients, reduce morbidity rates and improve efficiency.

Clinical Responses and Follow-up Evaluation after Anti-TNF Treatment in Patients with Rheumatoid Arthritis at a Tertiary-care Hospital

Clinical Responses and Follow-up Evaluation after Anti-TNF Treatment in Patients with Rheumatoid Arthritis at a Tertiary-care Hospital

Adherence to Subcutaneous Anti-TNF Treatment in Chronic Inflammatory Rheumatism and Therapeutic Patient Education.

ObjectivePoor patient adherence to anti-TNF treatment has proven to be a major roadblock to effective management. Therapeutic patient education (TPE) is now recognized as a crucial tool in managing conditions like chronic inflammatory rheumatism and in improving treatment adherence. This study aimed to assess whether different TPE programs might improve adherence to subcutaneous anti-tumor necrosis factor (anti-TNF) treatment in patients with rheumatoid arthritis (RA), ankylosing spondyloarthritis (AS), and psoriatic arthritis (PsA).MethodsThis was a retrospective, observational, monocentric study of current care practices. We included 193 patients (124 women; mean age 53.3 ± 14.8 years). All patients received subcutaneous anti-TNF treatment and one of three TPE models, delivered by a nurse, from 2009 to 2013. The cohort was grouped according to different educational models: M1: information (N=92); M2: individual TPE (N=80); and M3: individual and group TPE sessions (N=21). Adherence was assessed with the Morisky Medication Adherence Scale (MMAS-4™). Scores were rated as follows: good adherence (MMAS-4 = 4), moderate adherence (MMAS-4 = 2–3), and poor adherence (MMAS-4 = 0–1).ResultsThe mean disease duration was 10 years [95% CI: 5 to 18]. The cohort comprised 113 patients with RA, 73 with AS, and seven with PsA. Overall, 146 (75.7%) patients displayed good adherence, 34 (17.6%) displayed moderate adherence, and 13 (6.7%) displayed poor adherence. The M3 group displayed less adherence than the M1 and M2 groups. Old age was the only factor correlated with good adherence (p=0.005). The level of knowledge had no significant impact on adherence.ConclusionThis study demonstrated good adherence to anti-TNF treatment in patients that received TPE, particularly when it was delivered in individual sessions.

Failure of anti-TNF treatment in patients with rheumatoid arthritis: The pros and cons of the early use of alternative biological agents.

The five TNF inhibitors currently approved for the treatment of RA are characterised by differences in their molecular structures, half-lives, administration routes, dosing intervals, immunogenicity, and use in women who wish to become pregnant. TNF inhibitors still represent the first biologic after conventional synthetic DMARD (csDMARD) in the majority of patients according to registry data. This was possibly because they were historically the first biological agents available (biological DMARDS with a different mechanism of action or targeted synthetic DMARDs did not become available until 2006s), and so switching from one to another was frequent in the case of an inadequate response and/or side effects. TNF inhibitors are also efficacious for other inflammatory joint and spine diseases, and have been approved for inflammatory bowel disease, uveitis and psoriasis. In addition, national registries have provided long-term safety data and demonstrated their beneficial effect on cardiovascular morbidity and mortality. However, approximately 30-40% of patients discontinue anti-TNF treatment because of primary failure, secondary loss of response, or intolerance. The options for managing anti-TNF treatment failures include switching to an alternative anti-TNF (cycling) or to another class of targeted drug with a different mechanism of action (swapping). The aim of this review is to evaluate the pros and cons of whether it is more appropriate to choose a second anti-TNF biological agents after the failure of the first or swap treatment early.

C3 AND C4 COMPLEMENT – BIOMARKERS FOR PROGNOSIS OF TREATMENT OF TNF-BLOKERS

Introduction: The complement system adds antibodies and helps phagocytic cells to destroy pathogens from the body. This is part of a congenital immune system that is not adaptive and does not change over the individual life. However, complement can be "triggered" by the adaptive immune system. The complement system is the main effector of the humoral patr of the immune system. Activation of complement results in opsonization, chemotaxis and cytolysis. Regulation of the complement system can control inflammatory diseases including psoriatic arthritis and vice versa, complement fixation disorders can lead to illness. Treatment with anti-TNF blokers complement activity in patients with inflammatory joint diseases.Objective: To investigate C3, C4 fractions of complement, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement the response prediction and monitoring of anti-TNF treatment in patients with psoriatic arthritis.Materials and Methods: 36 patients were included sequentially before treatment with TNF-a-blokers. C3, C4, ESR, CRP were assessed at baseline at 6 and 12 months after initiation of treatment with TNF-α blockers. The activity of the disease is measured by the DARSA disease activity scale, the responses being compared with a control group of persons similar in gender and age. Statistical data processing was performed using the SPSS v25.Results and conclusions: According to the results obtained, C3 and C4 were significantly higher than controls at initiation of treatment (C3 111.3 ± 30.8, C4 91.9 ± 12.4 mg / dl, controls 19.1 ± 8.3 mg / dl, 10.2 ± 5.6 mg / dl p = 0.001, p = 0.001). At 6 and 12 months of follow-up, 76.2% of patients had a reduction in the level of C3 and C4 (p = 0.002, 0.001, respectively). It was found that higher baseline levels of C3 were associated with higher DARSA values at 6 and 12 months.Conclusion: The study of the C3 and C4 complement fractions can be used as biomarkers to estimate the prognosis of TNF-blocker therapy.

Bimodal Function of Anti-TNF Treatment: Shall We Be Concerned about Anti-TNF Treatment in Patients with Rheumatoid Arthritis and Heart Failure?

Treatment with anti-TNF-α (tumor necrosis factor), one of the pivotal cytokines, was introduced to clinical practice at the end of last century and revolutionized the treatment of rheumatoid arthritis (RA) as well as many other inflammatory conditions. Such a treatment may however bring many safety issues regarding infections, tuberculosis, as well as cardiovascular diseases, including heart failure. Given the central role of proinflammatory cytokines in RA, atherosclerosis, and congestive heart failure (CHF), such a treatment might result in better control of the RA process on the one side and improvement of heart function on the other. Unfortunately, at the beginning of this century two randomized controlled trials failed to show any benefit of anti-TNF treatment in patients with heart failure (HF), suggesting direct negative impact of the treatment on morbidity and mortality in HF patients. As a result the anti-TNF treatment is contraindicated in all patients with heart failure and a substantial portion of patients with RA and impaired heart function are not able to benefit from the treatment. The role of TNF in CHF and RA differs substantially with regard to the source and pathophysiological function of the cytokine in both conditions, therefore negative data from CHF studies should be interpreted with caution. At least some of RA patients with heart failure may benefit from anti-TNF treatment, as it results not only in the reduction of inflammation but also contributes significantly to the improvement of cardiac function. The paper addresses the epidemiological data of safety of anti-TNF treatment in RA patients with the special emphasis to basic pathophysiological mechanisms via which TNF may act differently in both diseases.

Changes in T cell effector functions over an 8-year period with TNF antagonists in patients with chronic inflammatory rheumatic diseases

The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNγ by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment. Age-matched healthy donors were enrolled as controls. The quantitative mitogen-induced IFNγ responses significantly increased with respect to baseline at each time point, apart from the determination after 4 years. We found an increased expression of CD25/CD134 in CD4+ compared to CD8+ T cells both in patients and controls. The in vitro addition of anti-TNF agents induced a significant decrease of both the IFNγ response and of CD25/CD134, whereas no effect on the intensity of the proliferative response was observed. Our data provide a biological basis for the reassuring issues on the safety of long-term anti-TNF treatment in patients with IMID.

Predictive value of serum calprotectin (S100A8/A9) for clinical response after starting or tapering anti-TNF treatment in patients with rheumatoid arthritis

ObjectivesCalprotectin (S100A8/A9) has been correlated with disease activity in rheumatoid arthritis (RA). The aim of this study was to investigate the predictive value of serum calprotectin for clinical response after...

P728 Efficacy of anti-TNF treatment in patients with refractory ulcerative proctitis: Results from a French retrospective multi-centre national cohort

P728 Efficacy of anti-TNF treatment in patients with refractory ulcerative proctitis: Results from a French retrospective multi-centre national cohort

P189 Diffusion-weighted magnetic resonance enterography for prediction of response to tumour necrosis factor inhibitors in stricturing Crohn’s disease

Patients with Crohn’s disease (CD) frequently develop intestinal strictures that are a major cause of surgical and endoscopic interventions. Predominantly fibrotic strictures are less likely to respond to anti-inflammatory therapy. None of the currently available diagnostic modalities can reliably distinguish between fibrotic and inflammatory strictures. The capacity of diffusion-weighted (DWI) magnetic resonance (MRE) to identify intestinal fibrosis was recently demonstrated; however the therapeutic implications of this association have never been evaluated. The aim of the current study was to identify the imaging factors associated with response to anti-inflammatory treatment in patients with stricturing CD. Consecutive CD patients with intestinal strictures that initiated treatment with anti-tumour necrosis alpha (anti-TNF) between June 2012 and April 2017 with MRE adjacent to treatment ONSET were retrospectively collected. Patients with previous intestinal surgery or active penetrating complications on index MRE were excluded. The primary outcome was treatment failure, defined as drug discontinuation, CD-related surgery or endoscopic dilatation of the stricture. Clinical, demographic and imaging parameters including stricture length, prestenotic dilatation diameter, presence of ulcers, apparent diffusion coefficient (ADC), relative contrast enhancement (RCE), magnetic resonance index of activity (MaRIA) and Clermont score were compared between patients who did and did not develop treatment failure within 12 months of anti-TNF treatment. A total of 21 patients were included in the study; 9/21 (42.8) developed treatment failure. None of the clinical and demographic variables were associated with the likelihood of treatment failure. Among imaging parameters, only ADC (<1 x 10–3 mm2/s) was significantly associated with the risk of treatment failure (66% vs. 0%, p = 0.015, OR-30.1 (95% CI −1.2–785, AUC = 0.81). Our results suggest that ADC value on DWI MRE can predict the risk of treatment failure in stricturing CD. If replicated in larger studies, these results may guide therapeutic decisions and suggest avoiding anti-TNF treatment in patients with intestinal strictures with ADC <1 × 10–3 mm2/s.

Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease.

AIMTo investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn’s disease (CD).METHODSOne hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTSOne hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients’ characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.CONCLUSIONNo correlation is detected between studied polymorphisms and patients’ response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.

Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden.

The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up.