Use Of anti-TNFα Agents Research Articles

Impact of systemic treatments on the course of HLA-B27-associated uveitis: A retrospective study of 101 patients.

PurposeTo investigate the efficacy and tolerance of systemic treatments for the prevention of HLA-B27-associated acute uveitis (AU) recurrence.MethodsRetrospective review of patients with HLA-B27-associated uveitis followed in our tertiary center over a 15-year period. Systemic treatments were prescribed to patients with frequent (more than 2 flares per year) or severe uveitis, according to a step-up strategyResults101 patients (51.5% of men, 88.1% of white Europeans) with a median age of 37 years. AU was mostly recurrent (68.3%) and associated with spondyloarthritis (60.4%). After a median follow-up duration of 22 months (3–73), 37.6% of the patients have received systemic treatment. 88.5% of the patients have been treated with sulfasalazine (SSZ) for ophthalmologic purposes (23/26). Methotrexate (MTX) and anti-TNFα agents have been initiated for a rheumatologic indication in 81.8% (9/11) and 100% of the patients (13/13), respectively. The annual uveitis relapse rate significantly decreased on SSZ (0.37 recurrences/year versus baseline 2.46 recurrences/year; p<0.001) and MTX (1.54 recurrences/year versus 4.17/year; p = 0.008). Patients under ADA for ophthalmologic purposes (n = 2) did not experience any recurrence.ConclusionWe report an open-label strategy to prevent the recurrences of HLA-B27-associated AU. First-line sulfasalazine reduced uveitis relapses. The use of anti-TNFα agents for ophthalmologic purposes was unnecessary with rare exceptions.

Characterization of auto-immune hepatitis associated with the use of anti-TNFα agents: An analysis of 389 cases in VigiBase.

Auto-immune diseases, including auto-immune hepatitis may be associated with the use of drugs, such as anti-TNF-α inhibitors. The aim of the study was to analyze the characteristics of anti-TNF-α inhibitor-associated auto-immune hepatitis (ATIAIH) in a large international pharmacovigilance database. We analyzed all ICSRs classified as "Autoimmune hepatitis" according to the Medical Dictionary for Drug Regulatory Activities term (preferred term level) in VigiBase, the World Health Organization global pharmacovigilance database of adverse drug reactions collected by national drug authorities in >130 countries (>90% of the world population). Bayesian disproportionality analysis was used to compute IC025, which is the lower end of the 95% credibility interval for the association between a suspected treatment and an adverse event. IC025>0 are considered statistically significant. A total of 389 ATIAIH ICSRs were identified. The median age at ATIAIH onset was 44years and the female to male sex ratio was 3.72. Infliximab (IC025=2.98), adalimumab (IC025=0.32) and etanercept (IC025=0.19) yielded a statistically significant signal in disproportionality analysis. Infliximab was the most frequently involved drug (50.1%). The median treatment duration before ATIAH occurrence was 4.9months. ATIAIH was reported as serious adverse event in 91%. Death (directly linked to AIH or not) occurred in 10 cases (2.9% of ICSRs). The most frequent reported indication for anti-TNF-α agent was rheumatoid arthritis (31.9%). This study enables the identification and a detailed study of 389 new cases of ATIAIH and confirms a significant association of ATIAIH with infliximab, adalimumab and etanercept.

Paradigm Shift of Healthcare Cost for Patients with Inflammatory Bowel Diseases: A Claims Data-Based Analysis in Japan

Anti-tumor necrosis factor-α (anti-TNFα) agents are used for induction and maintenance of remission in patients with inflammatory bowel diseases (IBD). However, biologic drugs present a large economic burden on health insurance systems. We aimed to estimate the mean annual health care cost per patient with IBD and cost contribution of anti-TNFα agents. We performed an analysis of patients with Crohn’s disease (CD) and ulcerative colitis (UC) based on a large-scale administrative claims database constructed by Japan Medical Data Center (JMDC) Co. Ltd., comprising inpatient, outpatient, and pharmacy claims data. We evaluated all claims from 1 April 2013 through 31 March 2016. Descriptive statistics were used to measure median health care costs paid per member per year (PMPY) and the relative cost contribution of anti-TNFα agents. A total 1405 patients with CD and 5771 with UC were included. Median costs PMPY were approximately six times higher for CD than UC (JPY 1,957,320 and JPY 278,760, respectively). Medication cost for anti-TNFα agents was the main cost driver, accounting for 59.9% and 17.8% of the total costs for CD and UC, respectively. In Japan, costs for anti-TNFα agents have resulted in drug costs exceeding inpatient costs for IBD. Optimized use of anti-TNFα agents and introduction of biosimilars for anti-TNFα agents can be expected to substantially reduce the health care costs of IBD.

Use of Anti-TNFα Agents and Time to First-time Surgery in Paediatric Patients with Ulcerative Colitis and Crohn's Disease.

It is debated whether the need for surgery has changed following introduction of anti-TNFα agents in the treatment of paediatric ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to describe the implementation of anti-TNFα agents in paediatric patients, and the need of first-time surgery before and after introduction of anti-TNFα agents. In the Danish National Patient Registry, we identified incident paediatric patients diagnosed from 1998. We calculated the proportion of patients receiving anti-TNFα agents within 5 years from diagnosis, and the cumulative 5 year proportion of surgery, according to calendar periods of diagnosis. At the end of our study period [2007 and 2008], 29-41% of CD children were treated with anti-TNFα agents within 5 years, and for UC children 17-19%. In 1278 CD patients, the 5 year cumulative proportions of surgery were 14.6-15.6% for children diagnosed in 1998-2008 and 9.7% (95% confidence interval [CI]: 6.7-13.7) for those diagnosed in 2009-2013. In 1468 UC patients, the cumulative proportion of surgery suggested a decline in patients diagnosed after mid 2005, and the hazard ratio of surgery was 0.64 [95% CI: 0.47-0.86] after the introduction of anti-TNFα agents compared with before. For UC patients diagnosed in 2009-2013, the 5 year cumulative proportion of surgery was 7.6% [95% CI: 5.2-11.2]. This nationwide study showed an extensive use of anti-TNFα agents at the end of our study period. For UC children, our data suggest a decline in the proportion of surgery in the period of increasing use of anti-TNFα agents.

Malignancy risk of anti-tumor necrosis factor alpha blockers: an overview of systematic reviews and meta-analyses.

The objective of the study is to systematically review the malignancy risk of anti-tumor necrosis factor alpha (anti-TNFα) agents. Databases of PubMed Medline, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses of randomized control trials, observational studies, and case series that evaluated malignancy risk of anti-TNFα blockers. Search time duration was restricted from January 1st, 2000 to July 16th, 2015. Overview Quality Assessment Questionnaires were used to assess the quality of included reviews. Two methodology trained reviewers separately and repeatedly screened searched studies according to study selection criteria, collected data, and assessed quality. Totally, 42 reviews proved eligible with only one Cochrane review. Anti-TNFα antagonists were extensively used to treat various diseases; nevertheless, malignancy risks were most commonly described in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In RA patients, no increased risks of breast cancer, lymphoma, and non-melanoma skin cancer were found, but if the use of anti-TNFα agents was associated with elevated risk of overall malignancy was still uncertainty. In IBD patients, the use of anti-TNFα inhibitors was not connected with enhanced risk of overall cancer. No increased cancer risk was found in other disease conditions. Twenty-nine reviews were rated as good quality, 12 as moderate, and one as poor. There are no sufficient evidences to draw the conclusion that anti-TNFα blockers have relationship with increased malignancy risk.

The use of anti-TNF therapy for ankylosing spondylitis in everyday rheumatology practice and the relationship to disease activity, work disability and diagnostic delay

Ankylosing spondylitis (AS) is characterised by insidious onset lower back pain. Poor symptom recognition results in delays in diagnosis of up to 11 years. Despite the widespread use of anti-tumour necrosis factor alpha (anti-TNFα) therapy, work disability remains a challenging problem in AS. A retrospective review of AS patients attending our physiotherapy service was carried out. Data regarding patient demographics, delay in diagnosis, treatment and disease activity were recorded. Ninety-two patients were identified of which 80 % were male. Just over 60 % of patients were on treatment with a TNF inhibitor and the average delay in diagnosis was 6 years. Clinically relevant changes in disease activity after 3 months of anti-TNFα therapy were demonstrated with a reduction in Bath AS Metrology Index, Bath AS Functional Index and Bath AS Disease Activity Index of 1, 1.99 and 2.39, respectively. In patients under the age of 65 years only 55.4 % of patients were employed. There was no relationship identified between diagnostic delay, employment status and treatment with an anti-TNF agent. Delays in diagnosis of AS remain unacceptably high; however, delays of 6 years compare favourably to reported data. Despite this and the appropriate use of anti-TNFα agents, we continue to see high rates of unemployment in this patient group which can impact both on the person and society and bears further consideration.

AB0750 Long-term efficacy and safety of anti TNF-α therapy in 4 patients with refractory takayasu’s arteritis

BackgroundTakayasu arteritis (TA) is a chronic large vessel vasculitis of an unknown cause, affecting the aorta and its primary branches, that leads to wall thickening, stenosis and thrombus or anuerysm...

THU0391 Anti-TNF therapy in severe and refractory sarcoidosis: Multicenter study of 25 patients

BackgroundSarcoidosis is a systemic granulomatous autoimmune disease. Clinically it may range from a mild to a severe life-threatening disease.ObjectivesTo assess the efficacy of anti-TNFα therapy in refractory and severe sarcoidosis.MethodsWe...

A dramatic case of Behçet disease successfully treated with infliximab

Behçet disease is a chronic relapsing systemic disease with possible life-threatening presentations. Management of this disease can be challenging and reports of the off-label use of anti-TNFα agents for the treatment of severe manifestations are increasing, with good results. The authors report a case of Behçet disease with a sudden and severe multi-systemic onset successfully treated with infliximab.

Compliance with NICE guidance on the use of anti-TNFα agents in ankylosing spondylitis: an East and West Midlands regional audit

Here we report on an audit performed to examine compliance with National Institute for Health and Clinical Excellence (NICE) guidelines for the use of anti-tumour necrosis factor alpha (anti-TNFalpha) in treating patients with ankylosing spondylitis (AS). Data from 17 rheumatology centres across the Midlands were collected prospectively from patients with AS attending outpatient clinics and retrospectively in patients receiving anti-TNFalpha but not attending outpatient clinics during the audit. In total, 80% of the 416 patients for whom data were collected were male. Of the 238 patients recruited prospectively, 41% were receiving anti-TNFalpha. Reviewing all patients on anti-TNFalpha (N=275), pre-treatment assessments 12 weeks apart were documented in 55% of patients. After anti-TNFalpha treatment had started, regular 12-weekly assessments occurred in 46% of patients. Therefore, compliance with NICE guidance was found to vary among centres. Based on our audit, clinical capacity, and clinical or patient choice might be influencing the suboptimal adherence seen in assessment timing suggested by NICE guidelines relating to the use of anti-TNFalpha in treating patients with AS.

Is continuation of anti-tumor necrosis factor-α therapy a safe option for patients who have developed pulmonary mycobacterial infection?

Continuation of anti-tumor necrosis factor-α (TNFα) therapy generally has not been recommended for patients who have developed nontuberculous mycobacterial (NTM) diseases; in daily practice, however, we often encounter patients with refractory rheumatoid arthritis (RA) who experience uncontrollable flares following withdrawal of anti-TNFα agents. Here, we report a case of pulmonary NTM disease caused by Mycobacterium intracellulare occurring in a patient with refractory RA undergoing etanercept therapy. Since there was the concern of an exacerbation of RA symptoms, etanercept was continued during anti-NTM therapy. The patient's pulmonary symptoms and radiological abnormalities were found to have markedly improved in a relatively short time period after beginning the anti-NTM therapy. Additionally, her RA symptoms were adequately controlled without the occurrence of any unexpected adverse events. The continuation of etanercept therapy may be a safe option during anti-NTM therapy if patients' underlying diseases would otherwise be difficult to control. Strictly supervised anti-NTM therapy and patients' informed consent are mandatory. We review the medical literature on NTM disease associated with anti-TNFα therapy for rheumatic diseases and discuss the safety of simultaneous use of anti-TNFα agents in patients during anti-NTM therapy.

Safety of anti‐tumour necrosis factor‐α agents in psoriasis patients who were chronic hepatitis B carriers: a retrospective report of seven patients and brief review of the literature

Issues concerning the potential risks of reactivating chronic hepatitis B virus arise when the use of anti-Tumour Necrosis Factor-α (TNFα) agents is imperative in patients with concurrent psoriasis and hepatitis B virus infection. The aim of this study was to report the experience regarding safety in the management of patients with coexisting psoriasis and chronic hepatitis B with the anti-TNFα agents: infliximab, etanercept and adalimumab. The psoriasis outpatient database of our dermatological department was searched for psoriasis and hepatitis B diagnoses and the medical records of these patients were reviewed for use of anti-TNFα agents. Seven cases (four women and three men) were identified, with mean age of 51years (34-65years). Three patients received adalimumab, three patients were given etanercept and one infliximab. All patients received lamivudin, 100mg/day, which started 2weeks before the initiation of anti-TNFα medication and went on during the whole treatment period. Follow-up period extended from 6-24months. All patients were inactive HbsAg (+) carriers. Liver function tests - at baseline and at the end of follow-up period - were within the normal range. There was no considerable rise in the viral load in any case, from baseline until the last available measurement, although a patient receiving infliximab showed an increase that reached 600 IU/mL. Successful treatment of psoriasis with anti-TNFα agents in patients who are inactive HBsAg carriers is possible and could be safe under the conditions of concomitant lamivudin administration and intensive monitoring. Larger randomized controlled studies are needed to confirm these findings.

The Guideline and Safety Manual for Use of Anti-TNFαAgents in Psoriasis

The Guideline and Safety Manual for Use of Anti-TNFαAgents in Psoriasis

Appropriate maintenance treatment for Crohn's disease: Results of a multidisciplinary international expert panel — EPACT II

Introduction Biological therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNFα inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7–9), uncertain (4–6 and/or disagreement) and inappropriate (1–3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNFα antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a “wait-and-see” strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNFα agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNFα agents are now freely available online ( www.epact.ch). The validity of these criteria should now be tested by prospective evaluation.

Clinical significance of synovial lymphoid neogenesis and its reversal after anti-tumour necrosis factor α therapy in rheumatoid arthritis

Objective:To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), the clinicopathological correlates of this process and its evolution after anti-tumour necrosis factor (TNF)α therapy in a...

Autoimmune diseases

The past two to three years have seen rapid developments in the use of biological therapies to treat the major autoimmune rheumatic diseases. In this review we will focus on the rapid accumulation of data encouraging this approach. Randomized controlled trials using the three tumour necrosis factor (TNF)α inhibitors on the market (infliximab, etanercept and adalimumab) have confirmed, not only the clinical efficacy of TNFα blockade, but also its benefit on radiographic progression of joint erosion in patients with rheumatoid arthritis (RA) and psoriatic arthritis, and on spinal inflammation in patients with ankylosing spondylitis (as measured by magnetic resonance imaging). The impact of anti-TNFα blockade on survival of patients is an important ongoing topic. Some critical, still unresolved, questions about the use of anti-TNFα agents have emerged. Finally, the current role of B cell depletion with rituximab for the treatment of patients with systemic lupus erythematosus is also analysed. The past two to three years have seen rapid developments in the use of biological therapies to treat the major autoimmune rheumatic diseases. In this review we will focus on the rapid accumulation of data encouraging this approach. Randomized controlled trials using the three tumour necrosis factor (TNF)α inhibitors on the market (infliximab, etanercept and adalimumab) have confirmed, not only the clinical efficacy of TNFα blockade, but also its benefit on radiographic progression of joint erosion in patients with rheumatoid arthritis (RA) and psoriatic arthritis, and on spinal inflammation in patients with ankylosing spondylitis (as measured by magnetic resonance imaging). The impact of anti-TNFα blockade on survival of patients is an important ongoing topic. Some critical, still unresolved, questions about the use of anti-TNFα agents have emerged. Finally, the current role of B cell depletion with rituximab for the treatment of patients with systemic lupus erythematosus is also analysed.

Developments and current pharmacotherapeutic recommendations for ankylosing spondylitis

The introduction of anti-TNFα therapy into the field of rheumatology has led to dramatic improvements in patient care, perhaps the most remarkable being in the management of ankylosing spondylitis. As experience with these compounds grows, their place in therapeutic strategy is becoming clearer, and it has been possible to develop evidence- and expertise-based recommendations for the management of ankylosing spondylitis to aid the clinician in patient care. This review outlines treatment advances in ankylosing spondylitis, including the use of anti-TNFα agents, and how these have been incorporated into clinical recommendations for daily use.