anti-TNF Biologics Research Articles

AB0672 Serological Neo-Epitope Biomarkers of Synovial Associated Collagen Can Assess Treatment Efficacy of Anti-TNF-A and Identify Benefiters

BackgroundNon Steroidal Anti-Inflammatory Drugs (NSAIDs) and anti-TNF biologics have been used in patients with ankylosing spondylitis (AS) to suppress inflammation and associated symptoms. Although symptom-modifying, the effects of these interventions...

OP0170 Infection Risk by Type and Treatment for Patients with Rheumatoid Arthritis (RA)

BackgroundThe specific impact of disease measures and current treatments on the risk of serious infections for patients with Rheumatoid Arthritis (RA) are still unknown. In addition, few have examined these...

AB0825 Investigation of Effects on Bone Metabolism of Anti-TNF BIOLOGICS and Bisphosphonates in Patients with Rheumatoid Arthritis

BackgroundTreatment for rheumatoid arthritis has become to obtain remission as biologics are widely used. Nonetheless, the main target of the treatment is synovitis and evaluation and treatment for osteoporosis with...

PSY34 - Cost-Minimization Analysis Of Anti-Tnf Biologics In The Treatment Of Rheumatoid Arthritis, Ankylosing Spondylitis And Psoriatic Arthritis Under The Brazilian Public Health Care System (Sus) Perspective

PSY34 - Cost-Minimization Analysis Of Anti-Tnf Biologics In The Treatment Of Rheumatoid Arthritis, Ankylosing Spondylitis And Psoriatic Arthritis Under The Brazilian Public Health Care System (Sus) Perspective

Remission in patients with active rheumatoid arthritis by tocilizumab treatment in routine clinical practice: results from 3 years of prospectively registered data

Objectives. This study aimed to evaluate the remission in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ), based on prospectively registered data in clinical practice.Methods. We studied 114 consecutive RA patients treated with TCZ for an average of 3.5 years. Remission was evaluated by using the EULAR criteria and the new ACR/EULAR Boolean-based criteria.Results. Among 114 patients (average age 52.2 years; average disease duration 10.6 years), 76 (67 %) had previously received anti-TNF biologics. Mean baseline DAS28-ESR of 5.4 and improved to 2.4 at 36 months. Overall, DAS28-ESR <2.6 was attained by 66.7 %, while ACR/EULAR remission was attained by 35.1 %. ACR/EULAR remission rate was significantly higher in the patients who were biologics-naïve and had good response at the first month. Among 23 patients who completed the treatment for 3 years and had ACR/EULAR remission at 1 year, 15 (65 %) remained in the remission and 16 (70 %) had a DAS28-ESR <2.6 at the final follow-up. The retention rate at 36 months was 68.2 %.Conclusions. In patients with RA, TCZ is highly effective for both biologics-naïve patients and patients previously exposed to biologics, achieving a high remission rate and drug continuation rate (68.2 %) in clinical practice.

TNF blocking therapies and immunomonitoring in patients with inflammatory bowel disease.

Since their appearance in the armamentarium for inflammatory bowel disease (IBD) more than a decade ago, antitumor necrosis factor (TNF) inhibitors have demonstrated beneficial activity in induction and maintenance of clinical remission, mucosal healing, improvement in quality of life, and reduction in surgeries and hospitalizations. However, more than one-third of patients present primary resistance, and another one-third become resistant over time. One of the main factors associated with loss of response is the immunogenicity of anti-TNF biologics leading to the production of antidrug antibodies (ADAbs) accelerating their clearance. In this review we present the current state of the literature on the place of TNF and its blockage in the treatment of patients with IBD and discuss the usefulness of serum trough levels and ADAb monitoring in the optimization of anti-TNF therapies.

Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis

The way rheumatoid arthritis is treated has changed dramatically with the introduction of anti-tumor necrosis factor (anti-TNF) biologics. Nevertheless, many patients still have less than adequate control of their disease activity even with these therapeutic regimens, and current knowledge fails to explain all the data already gathered. There is now a wide range of drugs from different classes of biologic disease-modifying anti-rheumatic drugs available (and soon this number will increase significantly), that provides the opportunity to address each patient as a particular case and thereby optimize medical intervention. Currently available biologics for the treatment of rheumatoid arthritis apart from anti-TNF-based therapies are reviewed, along with an analysis of the new insights they provide into the pathogenesis of the disease and a discussion of future prospects in the area.

A Case of Colchicine-refractory Familial Mediterranean Fever and Lessons for IBD

Purpose: A 22-year-old woman with familial Mediterranean fever (FMF) treated with colchicine and a strong family history of Crohn's disease presented with severe lower abdominal pain, nausea, vomiting and fevers up to 104 F. The differential diagnosis for her symptoms included Crohn's, ulcerative colitis, appendicitis, intussusception, cholecystitis, pelvic inflammatory disease, peptic ulcer and colchicinerefractory FMF flare. Physical exam was unremarkable, except for abdominal tenderness predominantly in the RLQ with modest guarding. Laboratory evaluation showed normal electrolytes, CBC, amylase/lipase, TFTs, PTH and vitamin levels. Stool and urine cultures were negative. Gynecologic evaluation, including transvaginal ultrasound, was normal. MRE showed no evidence of bowel wall inflammation or obstruction. Upper endoscopy biopsies showed a chronic chemical gastropathy with no Barrett's, no H. pylori, and normal jejunal villous architecture. Colonoscopy was normal, with normal terminal ileum and colonic mucosal biopsies. Given the recurrence of symptoms and greater than one febrile attack per month, the patient was deemed to have colchicine-resistant FMF and was referred to rheumatology for initiation of anti-IL1β biologic therapy. Discussion: FMF is a hereditary auto-inflammatory disease characterized by periodic fevers and serositis triggered by deregulated inflammasome production of IL-1β. With peritonitis, abdominal pain and fever being the most common manifestations, gastroenterologists need to consider FMF in the DDX of IBD-associated inflammatory symptoms. FMF is caused by mutations in the MEFV gene encoding pyrin. Mutant pyrin fails to regulate caspase-1 activity and additionally activates NFκB. Careful follow-up of FMF patients is critical as they are at increased risk of developing late-onset IBD. This increased risk for IBD may be related to the close association of the CD-susceptibility gene NOD2 with the MEFV gene on chromosome 16. Pyrin also interacts with the innate immune intracellular NOD-like receptor Nlrp3, which has been shown to contribute to Crohn's susceptibility. Nlrp3 is a crucial regulator of intestinal homeostasis, mediating assembly of the inflammasome complex in the presence of microbial ligands, triggering caspase-1 activation and secretion of IL-1β and IL-18. Although colchicine is the first line of treatment for FMF, case reports have shown some efficacy with anti-TNF biologics. However, IL-1β biologics are emerging as the best second-line therapy for colchicine-resistant FMF patients. Despite the FMF and IBD overlap in inflammasome deregulation of the IL-1β pathway, studies are lacking on the effectiveness of colchicine or anti-IL-1β therapy for IBD.

Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis refractory to anti-tumor-necrosis-factor inhibitors: 1 year follow-up with low-field extremity MRI

Objective Tocilizumab (TCZ) is effective in patients with rheumatoid arthritis (RA) who are refractory to anti-tumor-necrosis-factor (anti-TNF) biologics. The Rheumatoid Arthritis Society Disease Activity Score in 28 Joints (DAS28) is used to evaluate the response to TCZ. However, DAS28 is inappropriate marker because TCZ normalizes C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the early stage of treatment. The aim of our study was to test the usefulness of magnetic resonance imaging (MRI)-based markers of response to TCZ treatment.Methods Nine patients with RA who were refractory to anti-TNF inhibitors (six to infliximab, one to etanercept, one to adalimumab, and one to both) were assessed. MRI images of both hands were obtained by low-field extremity MRI at baseline, 20, and 44 weeks of treatment, in addition to assessment with DAS28–ESR. The effect of TCZ on RA was examined by compact MRI score (cMRIS).Results All patients showed good or moderate response to TCZ treatment, as evaluated by significant reduction in DAS28–ESR at both 20 and 44 weeks (p < 0.001, each, relative to baseline). In contrast, MRI-based indexes (e.g., cMRIS, synovitis, edema, erosion scores) improved significantly at 44 weeks but not at 20 weeks.Conclusion Differences in response to TCZ therapy were determined based on the method of evaluation, suggesting that MRI-based markers are potentially useful for evaluating RA response to TCZ therapy.

AB0521 Differences in disease characteristics of patients with active psoriatic arthritis prior to adalimumab treatment who failed at least two antitnf-therapies in comparison to those who failed conventional dmards only

BackgroundFor the treatment of patients with active psoriatic arthritis (PsA) only antiTNF biologics are licensed. Therefore, failures to anti-TNF are often switched to another antiTNF treatment. In this study, characteristics...

FRI0195 Treatment with anti-tnf biologics in patient with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis does not increase the risk of malignancy

BackgroundSystemic inflammatory rheumatic diseases, may increase the risk of malignancy, and in particular of lymphoproliferative disorders1. If anti-TNFα therapy is associated with this risk is still controversial2,3.ObjectivesThe aim of this...

AB0453 Retention rate of the anti-TNF biologics in the treatment of rheumatic diseases and predictive factors for drug withdrawal: Data from the hong kong biologics registry

ObjectivesTo study the retention rate of the anti-TNF biologics in the treatment of rheumatic diseases and the associated factors for drug withdrawalMethodsThe Hong Kong Biologics Registry was established in 2005....

THU0352 Long-Term Safety and Efficacy of Golimumab in the Treatment of Ankylosing Spondylitis: Results Through 5 Years of the Go-Raise Trial

BackgroundGolimumab(GLM) has demonstrated significant and sustained clinical efficacy and an acceptable safety profile through 2yrs of the phase 3, randomized, PBO-controlled, GO-RAISE study in pts with ankylosing spondylitis (AS).ObjectivesTo evaluate...

FRI0530 Factors influencing selection of biologic therapy and comparative effectiveness in patient reported outcomes among patients with rheumatoid arthritis

BackgroundBiologic use among patients with rheumatoid arthritis (RA) is increasingly common. Given different anti-tumor necrosis factor (TNF) options, a better understanding of factors that influence physicians’ and patients’ selection of...

OP0002 Use of anti-TNF therapy is associated with reduced cardiovascular event risk in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is associated with increased risks for cardiovascular (CV) comorbidities because of an increased prevalence of traditional CV risk factors and the underlying chronic inflammatory process.ObjectivesTo assess the...

THU0186 Anti-Drug Antibodies, Drug Levels and Clinical Efficacy of the Anti-TNF Biologics in Rheumatic Diseases

ObjectivesTo evaluate the effect of drug levels and anti-drug antibodies on the clinical efficacy and withdrawal of the anti-TNFa biologics in Chinese patients with rheumatic diseases.MethodsA cross-sectional study was performed...

SAT0113 Intense Repression of Serum Oxidative Stress Marker in Rheumatoid Arthritis Cases Treated with Tocilizumab: Cross Sectional and Longitudinal Evaluation

BackgroundOxidative stress induced by reactive oxygen species (ROS) is also an important mechanism that underlies destructive and proliferative synovitis in rheumatoid arthritis (RA). Abundant amounts of reactive oxygen species have...

AB0319 Treatment with tocilizumab improved rheumatoid arthritis patients clinically and structurally regardless of the prior use of anti-tnf biologics in daily clinical practice

ObjectivesTo explore the radiographic efficacy of tocilizumab (TCZ) in rheumatoid arthritis (RA) patients with or without the prior use of anti-tumor necrosis factor (TNF) agents in daily clinical practice.MethodsOf a...

Newest clinical trial results with antitumor necrosis factor and nonantitumor necrosis factor biologics for rheumatoid arthritis

To highlight recent evidence from the clinical trials of anti-tumor necrosis factor (TNF) and non anti-TNF biologics for rheumatoid arthritis (RA) focused on comparative clinical efficacy including safety outcomes and medication discontinuation. Patients with RA are sometimes able to attain low disease activity or remission since the introduction of biologic therapy for RA. Biologics like anti-TNF, anti-interleukin-6 (IL-6), anti-CD20 and those that modulate T-cell co-stimulation have consistently shown good efficacy in patients with RA. Preliminary data from comparative efficacy studies to evaluate the potential differences between anti-TNF and non anti-TNF biologics have shown little differences among these. There is ongoing work in comparative efficacy to answer this question further. Biologic therapy in RA has significantly changed the course of RA in the last decade. Recently published clinical trials have been focused on comparative efficacy, cardiovascular safety of biologics and potential anti-TNF therapy discontinuation in patients with RA.

Sa1202 Relationships Between Clinical Remission, C-Reactive Protein Normalization and Mucosal Healing in Crohn's Disease: Analyses From the SONIC trial

evaluate associations of SI and pts receiving anti-TNFa agents and immunomodulators (IM). We categorized SI events and evaluated pts who experienced SI within 91 days of IFX, other anti-TNFa exposure, or within 31 days of IM exposure. Results: 4343 pts (7883 pt-yrs [PY]) were enrolled as of 6/30/12, 2586 were exposed to anti-TNF biologics, including 2503 who received IFX (4347 PY). 1757 pts received only nonbiologic therapies (3369 PY). Factors associated with significant risk (p < 0.05) of SI were (adjusted hazard ratio, 95%CI): younger age at baseline (0.92, 0.86 0.97), hospitalizations in the year prior to enrollment (1.81, 1.27 2.59), time-dependent IFX use (2.00, 1.38 2.91), time-dependent IM use (1.58, 1.07 2.34), and time-dependent PGA score (1.23, 1.06 1.44) (time-dependent variables reflected response status at each 6-month visit for a pt). Pts with anti-TNF exposure in the last 91 days showed a significant increased risk of SI in the categories of number of SI (5.82 vs. 2.89 events per 100 pt yr for exposed vs. nonexposed), especially on the subcategories of superficial infections, & abdominal abscess; & a trend of an increased risk of significant viral infections. IFX exposed pts showed a trend of an increase risk of number of SI (4.88 vs. 3.65 events per 100 pt yr for exposed vs. nonexposed), & a significant increase risk on superficial infections. There were no differences in all categories for IM exposure within 31 days of SI. Conclusions: Time-dependent IFX use and hospitalizations in the year prior to enrollment conferred an approximate 2-fold increased risk for SI. Clinically significant risks for SI are associated with younger age, time-dependent IM use and timedependent higher PGA score. IFX and anti-TNF exposed pts have an increased risk in general of SI and of superficial infections within 91 days of exposure. Anti-TNF exposure appeared to increase the risk of abdominal abscess and significant viral infections. No difference in SI for IM exposure within 31 days was observed.