anti-TNF Inhibitors Research Articles

Selective inhibition of Tumor necrosis factor receptor-1 (TNFR1) for the treatment of autoimmune diseases

Anti-TNF biologics have achieved great success in the treatment of autoimmune diseases and have been the most selling biologics on market. However, the anti-TNF biologics have shown some disadvantages such as poor efficacy to some patients and high risk of infection and malignancies during clinical application. Current anti-TNF biologics are antibodies or antibody fragments that bind to TNF-α and subsequently block both TNF-TNFR1 and TNF-TNFR2 signaling. Transgenic animal studies indicate that TNFR1 signaling is responsible for chronic inflammation and cell apoptosis whereas TNFR2 signaling regulates tissue regeneration and inflammation. Recent studies propose to selectively inhibit TNFR1 to enhance efficacy and avoid side effects. In this review, we introduce the biology of TNF-TNFR1 and TNF-TNFR2 signaling, the advantages of selective inhibition of TNF-TNFR1 signaling and research updates on the development of selective inhibitors for TNF-TNFR1 signaling. Antibodies, small molecules and aptamers that selectively inhibit TNFR1 have showed therapeutic potential and less side effects in preclinical studies. Development of selective inhibitors for TNFR1 is a good strategy to enhance the efficacy and reduce the side effects of anti-TNF inhibitors and will be a trend for next-generation of anti-TNF inhibitors.

Biological Agents in OA - Hopes and Disappointments

Purpose: To review the trial in humans using biologics in osteoarthritis (OA) which can be can be categorized according to the main target: pain, structure or both. Methods: A literature review (Medline, Cochrane, Embase) of the most recent trials in OA using biologics Results: The analgesic effect of anti-nerve growth factor (NGF) was initially dramatic using high dose and intravenous route of administration, but emerging severe arthropathies (in the targeted knee but not only) have dampened down this enthusiasm. Most recent trials used anti NGF Mab, administered subcutaneously, with lower dose, shorter interval of administration and without concomitant use of NSAIDS. The effect on pain is still superior to placebo but with a much lesser magnitude. Unfortunately, long term follow-up in those trials still shows a concern in terms safety profile. Thus, Patients who will benefit of this anti NGF therapy should be strictly selected and followed up. Biologics agents targeting main cytokines (interleukines 1 and 6, tumor necrosis alpha) have been tested in knee OA and in hand OA. The first randomized controled trial in humans using a single local administration of the antagonist of IL-1, at 2 doses: 50 and 150 mg, failed to show an analgesic effect, except at day 3 with the highest dose. This negative result has been confirmed in trials using systemic administration of monoclonal antibodies directed against only IL1-β or against IL-1 α and Il-1 β in patients with knee OA and in patients with hand OA. However, in the CANTOR trial recruiting patients with cardiovascular disease treated with canakinumab, post hoc analysis indicated that the patients in the verum group, shows a dramatic decrease in the number of total joint replacement (hip and knee) (about 50%). This might open a door for a possible anti IL-1 strategy dedicated to patients with some part of systemic inflammation. Most of trial with anti TNF inhibitors have been performed in patients with erosive digital hand OA and all were negative on pain and on structure (measured by different parameters on magnetic resonance imaging). Finally the last cytokine that has been targeted is IL-6. Results of the RCP trial in hand OA are ongoing. Taking all together, biologics in OA are really disappointing, raising more questions than answers: choice of the targets, choice of selected phenotype of pain, selection of the route of administration, too short time of intra articular residence of the drug etc. News biologics targeting WNT, bradykinin or anti sense micro RNA are under development but so far, the preliminary results needs to be confirmed in large trials in humans. Finally, the last option is to try to stimulate the cartilage repair response which is naturally weak. Fibroblast growth factor 18 (sprifremin), an anabolic and mitogenic factor for the chondrocyte, has been tested against placebo in an ambitious trial over 5 years with 2 years of treatment and 3 years of follow-up. The drug was intra-articularly delivered every 6 months or every 12 months, with 2 different dosages. At the first end point, at year 2, with the highest dose of FGF-18, a statistically significant difference with the placebo was observed on the cartilage volume measured by MRI in the global, medial and lateral compartment on the involved knee. Unfortunately, there was no effect on pain in the ITT population, except in a sub group of patients with a minimum threshold of pain and an initial joint space width between 1.5mm and 3.5 mm (around one third of the population) show a significant effect on pain reduction compared to placebo. If results of this long term trial are confirmed in others trials, FGF-18 may constitute the first real disease modifying drug in OA. Conclusions Conclusion: The trials in humans using biologics are disappointing. We should keep in mind that blocking a single mediator will not stop the catabolic process in OA. Thus in the next future, we should probably adapt a drug owing to the evolution of the disease, to the profile of patient, to the radiological aspect of the disease and to the phenotype of pain. The story is just starting ⋯⋯

DOP72 Safety, tolerability and efficacy of anti-TL1A antibody PF-06480605 in treatment of ulcerative colitis: The open-label, multicentre, Phase 2a TUSCANY study

Abstract Background Widespread disruption of the mucosal immune system is central to the pathogenesis of ulcerative colitis (UC). One component, tumour necrosis factor (TNF) α-like ligand 1A (TL1A), is upregulated at the site of active disease in UC. Treatment of preclinical rodent models with anti-TL1A antibodies decreases disease activity, highlighting their therapeutic potential for UC. PF-06480605 is a first-in-class fully human immunoglobulin G1 monoclonal antibody targeting TL1A. Methods The Phase 2a, open-label, multicentre, single-arm TUSCANY study (NCT02840721) evaluated the safety, tolerability and efficacy of PF-06480605 in treatment of moderate to severe UC. Participants received 500 mg intravenous (IV) PF-06480605 every 2 weeks (Q2W) for a total of 7 doses, with a 14-week follow-up period. Primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and endoscopic improvement (EI) (Mayo endoscopic subscore [centrally read] of ≤1 without friability) at Week 14, respectively. Secondary efficacy endpoints included remission (total Mayo score ≤2, with no individual subscore >1) and endoscopic remission (Mayo endoscopic subscore = 0) at Week 14. Transcriptomic profiling on intestinal biopsies was performed. Results Of the 50 participants who received PF-06480605, 42 completed the study. The majority were male (56.0%) and white (96.0%), with a mean age of 40.0 years and prior experience of anti-TNF inhibitors (72.0%). Pancolitis (48.0%) and left-sided colitis (32.0%) were the most common forms of UC at baseline. There were 109 TEAEs, of which 18 were treatment-related. Aside from worsening UC, the most common TEAE by system organ class was arthralgia, which occurred in 6 participants, and 1 was treatment-related. Treatment-emergent serious adverse events were reported in 3 participants, and considered treatment-related in 1 participant (Table 1). No malignancies or deaths were reported. At Week 14, statistically significant EI was observed in 38.2% of participants (Table 2). The proportions of participants achieving remission and endoscopic remission at Week 14 were 24.0% and 10.0%, respectively. Transcriptomic analyses demonstrated normalisation towards a non-inflamed transcriptome in participants with EI. Conclusion PF-06480605 exhibited an acceptable safety and tolerability profile and statistically significant EI in participants with moderate to severe UC. These results warrant further evaluation in subsequent studies.

2169 Endoscopic Stricturotomy via Argon Plasma Coagulation With Balloon Dilation for Refractory Colonic Stricture Secondary to Crohn’s Disease

INTRODUCTION: Stricture is a significant complication in patients with Crohn’s disease (CD). Up to 80 % of patients will require at least one surgery for stricture, fistula, or abscess during their lifetime. The current treatment modalities are surgery, endoscopic balloon dilation (EBD), or endoscopic stricturotomy (ES) via a needle-knife or electrosurgical knife. We report a combined endoscopic stricturotomy via argon plasma coagulation (APC) with balloon dilation in a patient with refractory benign colonic stricture due to Crohn disease. CASE DESCRIPTION/METHODS: A 56-year old man with a twenty-seven-year history of Crohn’s disease presented to the clinic with chronic right-sided abdominal pain. He has two to three bowel movements a day. He is a non-smoker, denied alcohol, or illicit drug use. He had prior use of anti-TNF inhibitor with secondary loss of response. Current medication included azathioprine, esomeprazole, and ustekinumab injection every eight weeks. Vital signs were normal. The abdomen was soft, non-tender, no organomegaly, normal bowel sounds, and normal rectal exam. Labs revealed hemoglobin 14.2 g/dl, leukocyte count 7k/mm3, platelets 393k/mm3, urea nitrogen 13 mg/dl, creatinine 1.0 mg/dl, CRP 0.9, mg/dl and fecal calprotectin 59 ug/g. Magnetic resonance enterography (MRE) was performed and revealed severe short segment stricture of the mid ascending colon (Figure 1). He underwent a colonoscopy, and it showed a benign-appearing, severe non-traversed stricture measuring 3 cm in length x 1.1 cm in inner diameter in the ascending colon (Figure 2). Coagulation for tissue destruction and stricturotomy using pulsed argon plasma at 1.5 liters/minute and 40 watts was accomplished, followed by balloon dilator up to 15 mm with significant improvement in the luminal narrowing (Figure 3). The site was traversed, and the cecum was inspected. The patient was seen in the clinic two months later, and he was doing well, and his abdominal pain was resolved. DISCUSSION: Surgery is still considered to be the standard therapy in patients with a colonic stricture. Endoscopic stricturotomy has emerged as a promising modality to avoid or minimize the need for surgery. Up to our knowledge, using the APC mediated ES has not been reported. So, we report the successful use of this technique combined with balloon dilation in a patient with severe CD- associated benign stricture. The clinician should be aware of such procedure as an effective treatment modality in refractory benign colonic stricture.

The Association of Medications and Vaccination with Risk of Pneumonia in Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at increased risk for pneumonia, and corticosteroids are reported to amplify this risk. Less is known about the impact of corticosteroid-sparing IBD therapies on pneumonia risk or the efficacy of pneumococcal vaccination in reducing all-cause pneumonia in real-world IBD cohorts. We performed a population-based study using an established Veterans Health Administration cohort of 29,957 IBD patients. We identified all patients who developed bacterial pneumonia. Cox survival analysis was used to determine the association of corticosteroids at study entry and as a time-varying covariate, corticosteroid-sparing agents (immunomodulators and antitumor necrosis-alpha [TNF] inhibitors), and pneumococcal vaccination with the development of all-cause pneumonia. Patients with IBD who received corticosteroids had a greater risk of pneumonia when controlling for age, gender, and comorbidities (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.90-2.57 for prior use; HR = 3.42; 95% CI, 2.92-4.01 for use during follow-up). Anti-TNF inhibitors (HR 1.52; 95% CI, 1.02-2.26), but not immunomodulators (HR 0.91; 95% CI, 0.77-1.07), were associated with a small increase in pneumonia. A history of pneumonia was strongly associated with subsequent pneumonia (HR = 4.41; 95% CI, 3.70-5.27). Less than 15% of patients were vaccinated against pneumococcus, and this was not associated with a reduced risk of pneumonia (HR = 1.02; 95% CI, 0.80-1.30) in this cohort. In a large US cohort, corticosteroids were confirmed to increase pneumonia risk. Tumor necrosis-alpha inhibitors were associated with a smaller increase in the risk of pneumonia. Surprisingly, pneumococcal vaccination did not reduce all-cause pneumonia in this population, though few patients were vaccinated.

Psorijaziformna erupcija kao neželjeno dejstvo etanercepta - prikaz bolesnika

The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of etanercept for rheumatoid arthritis, developed psoriasis. After histopathological confirmation and consultation, the dermatologist concluded that psoriasis was a paradoxical effect of anti-TNF inhibitors. Anti-TNF inhibitor is replaced with other biological drugtocilizumab. After the change of the drug, psoriasis eruptions were completely resolved. The paradoxical form of psoriasis after the use of anti-TNF inhibitor requires a change of the drug with other mechanism of action

160 - Anti-TNF Inhibitors are not Associated with Increased Risk of Infection after Joint Replacement Surgery

160 - Anti-TNF Inhibitors are not Associated with Increased Risk of Infection after Joint Replacement Surgery

Effects of denosumab on bone metabolism and bone mineral density with anti-TNF inhibitors, tocilizumab, or abatacept in osteoporosis with rheumatoid arthritis.

IntroductionThe aim of this 18-month retrospective study was to evaluate the differences in outcomes of denosumab with tumor necrosis factor (TNF) inhibitors (TNFis), tocilizumab (TCZ), or abatacept (ABT) treatment in osteoporosis (OP) patients with rheumatoid arthritis (RA).Patients and methodsPatients were divided into TNFis-treated (TNF group; 44 cases), TCZ-treated (TCZ group; 8 cases), or ABT-treated (ABT group; 14 cases) groups. We measured serum bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) at baseline and every 3 months for 18 months and assessed bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and total hip BMD (H-BMD) at baseline and every 6 months for 18 months.ResultsThere were no significant differences in the percent changes in BAP, TRACP-5b, or L-BMD among the groups. The percent change in H-BMD was significantly increased in the TCZ group at 12 months or at 12 and 18 months, compared with that in the ABT group or TNF group, respectively. The percent change in L-BMD was significantly increased at 12 months in the TCZ and TNF groups, and at 18 months in all the 3 groups compared with pretreatment levels, whereas the percent change in H-BMD was significantly higher at 6, 12, and 18 months in the TCZ group, at 12 and 18 months in the TNF group, and at 18 months in the ABT group, compared with pretreatment levels.ConclusionOur findings suggest that TCZ might be more useful than TNF or ABT in light of the observed H-BMD increases with denosumab therapy for OP patients with RA.

Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti‐TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death. The blood–cerebrospinal fluid (CSF) barrier consists of a monolayer of choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE cell morphology. Here, we report that TNF is the main inflammatory upstream mediator in choroid plexus tissue in AD patients. This was confirmed in two murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv) AβO injection. TNFR1 contributes to the morphological damage of CPE cells in AD, and TNFR1 abrogation reduces brain inflammation and prevents blood–CSF barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued from the induced cognitive impairments. Our data indicate that TNFR1 is a promising therapeutic target for AD treatment.

Cutaneous Manifestations of Reactions to Biologics.

The goal of this paper is to review the major adverse cutaneous reactions that have been reported to the most commonly used biologics. Anti-TNF agents and immune checkpoint inhibitors have significant, immune-mediated cutaneous manifestations that can necessitate discontinuation. Anti-TNF agents, IL-6 inhibitors, and IL-12/23 inhibitors can paradoxically cause psoriasis flares or unmask previously undiagnosed psoriasis. IL-17 inhibitors are unique in increasing risk for Candida infections. Benign injection site reactions, non-specific rash, cellulitis, and hypersensitivity reactions are relatively common adverse events. A wide variety of cutaneous reactions caused by biologics have been reported, ranging from benign injection site reactions to life-threatening cutaneous reactions necessitating discontinuation of the implicated biologic agent.

Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis.

A natural killer group 2 member D (NKG2D) acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF) therapy is in rheumatoid arthritis (RA) patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G), rs1049174 (C > G), and rs1154831 (C > A). Clinical response was evaluated according to the European League against Rheumatism (EULAR) criteria at the 12th and 24th week. Both the NKG2D rs225336 and rs1049174 polymorphisms were significantly associated with efficacy of TNF inhibitors. Inefficient therapy was more frequently observed in patients with rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value = 0.003 and p-value = 0.004, respectively). The presence of the rs2255336 G or the rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p-value = 0.031, respectively). Moreover, patients carrying the rs2255336 or rs1049174 heterozygous genotype achieved better EULAR responses than patients with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively). Data from the present study provides evidence that NKG2D polymorphisms may affect response to anti-TNF inhibitors in RA patients.

TNF-α–induced protein 3 (TNFAIP3)/A20 acts as a master switch in TNF-α blockade–driven IL-17A expression

Anti-TNF inhibitors successfully improve the quality of life of patients with inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy, and some patients show paradoxical immune side effects, which are poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production with as yet unknown clinical implications. We sought to investigate the molecular mechanism underlying anti-TNF-driven IL-17A expression and the clinical implications of this phenomenon. Fluorescence-activated cell sorting, RNA sequencing, quantitative real-time PCR, Western blotting, small interfering RNA interference, and kinase inhibitors were used to study the molecular mechanisms in isolated human CD4+ T cells from healthy donors. The clinical implication was studied in blood samples of patients with inflammatory bowel disease (IBD) receiving anti-TNF therapy. Here we show that anti-TNF treatment results in inhibition of the anti-inflammatory molecule TNF-α-induced protein 3 (TNFAIP3)/A20 in memory CD4+ T cells. We found an inverse relationship between TNFAIP3/A20 expression levels and IL-17A production. Inhibition of TNFAIP3/A20 promotes kinase activity of p38 mitogen-activated protein kinase and protein kinase C, which drives IL-17A expression. Regulation of TNFAIP3/A20 expression and cognate IL-17A production in T cells are specifically mediated through TNF receptor 2 signaling. Exvivo, in patients with IBD treated with anti-TNF, we found further evidence for an inverse relationship between TNFAIP3/A20 expression levels and IL-17A-producing T cells. Anti-TNF treatment interferes in the TNFAIP3/A20-mediated anti-inflammatory feedback loop in CD4+ T cells and promotes kinase activity. This puts TNFAIP3/A20, combined with IL-17A expression, on the map as a potential tool for predicting therapy responsiveness or side effects of anti-TNF therapy. Moreover, it provides novel targets related to TNFAIP3/A20 activity for superior therapeutic regimens in patients with IBD.

Clinical Outcomes Associated with Switching or Discontinuation from Anti-TNF Inhibitors for Nonmedical Reasons

PurposeThis study evaluated clinical outcomes and health care resource utilization associated with nonmedical switching from or discontinuation of anti–tumor necrosis factor (TNF) therapies in US clinical practice. MethodsResponding physicians extracted data from the medical charts of patients with Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, or psoriatic arthritis who achieved response on an anti-TNF therapy. Physicians selected 2 cohorts of patients that were matched on diagnosis: patients who were switched/discontinued, for nonmedical reasons, from the anti-TNF therapy on which they achieved response (switchers/discontinuers), and patients who continued on their anti-TNF (continuers). Switchers/discontinuers were followed up for 12 months from the date of discontinuation (index date); continuers were followed up for 12 months from the date of an office visit within 2 months of the matched switcher/discontinuer׳s index date. Multivariate regression was used to compare disease flares, disease control, and health care resource utilization between cohorts, with adjustment for baseline characteristics. Subgroup analyses compared data from the continuer cohort to those from (1) patients who were switched to another biologic therapy and (2) patients who were switched to conventional therapy or discontinued from all therapy. FindingsA total of 377 matched pairs of continuers and switchers/discontinuers were analyzed (N = 754), with the latter cohort comprising 284 patients (73.3%) who were and 93 (24.7%) who did not switch to another treatment (biologic or conventional treatment) immediately after discontinuation. Switchers/discontinuers had more frequent flares than did continuers, across severity levels (adjusted incidence rate ratios = 1.67, 2.36, and 3.48 for mild, moderate, and severe flares, respectively; all, P < 0.05). Switchers/discontinuers had a lower rate of well-controlled disease symptoms (46.9% vs 88.1%; adjusted odds ratio = 0.11; P < 0.001). Switchers/discontinuers also had more frequent inpatient hospitalizations, emergency department visits, and outpatient visits (adjusted incidence rate ratios = 3.58, 5.73, and 1.12, respectively; all, P < 0.001). Findings from the subgroup analyses of data from the 183 patients who switched to a biologic therapy and 194 who switched to conventional therapy or discontinued from all therapy were largely consistent with the overall analysis. ImplicationsIn this study, switching/discontinuation from an anti-TNF therapy for nonmedical reasons was associated with significantly worse clinical outcomes and increased health care resource utilization—factors that should be considered when developing treatment algorithms.

Factors Associated with Discontinuation of Anti-TNF Inhibitors Among Persons with IBD: A Population-Based Analysis.

Antitumor necrosis factor (anti-TNF) medications are known to be highly efficacious in persons with moderate-to-severe inflammatory bowel disease (IBD). There is a paucity of data from population-based sources to elucidate persistence with these medications in the general population of IBD. Discontinuation of anti-TNF therapy is a marker of lack of effectiveness, intolerance, and patient/physician practice preferences. We identified all persons with IBD in Manitoba who were dispensed infliximab (IFX) and adalimumab (ADA) between 2001 and 2014. Subjects were followed longitudinally to assess rates of completion of anti-TNF induction, duration of continued use, intraclass substitution, and dose adjustments. Cox proportional hazards models were used to test demographic and clinical factors associated with anti-TNF therapy discontinuation. Overall, 925 of 8651 persons (10.7%) with IBD were prescribed an anti-TNF drug (705 Crohn's disease: 523 IFX and 182 ADA; 220 ulcerative colitis: 214 IFX and 6 ADA). Approximately four-fifths of persons starting on anti-TNF therapy completed induction. At 1 and 5 years, persistence rates with the original anti-TNF were approximately 60% and 40%, respectively. Immunomodulator use at the time of anti-TNF dispensation was associated with a decreased likelihood of anti-TNF discontinuation in both Crohn's disease and ulcerative colitis. ADA users with Crohn's disease who reached maintenance phase had a higher risk of discontinuation than IFX users (hazard ratio 1.64, 95% confidence interval 1.15-2.37). Approximately two-fifths of anti-TNF users discontinue use within 1 year of initiation, and three-fifths will have discontinued at 5 years. Concomitant IM therapy has a modest effect on discontinuation rates.

Biologicals in uveitis

Most noninfectious uveitis appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. Inflammatory uveitis is a difficult condition to treat. Recently, a new class of drugs obtained by a biological process and therefore defined as biologics has been successfully used in the treatment of immune-mediated rheumatic diseases. These drugs target different proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6 or immune effector cells including B- and T-lymphocytes. The success in rheumatology of the TNF-α inhibitors adalimumab (ADA) and infliximab (IFX) over the past several years has led to their use in uveitis, in particular in patients with Behcet's disease and for early use in patients with juvenile idiopathic arthritis who have not benefitted from methotrexate. The first experience with anti-TNF inhibitors etanercept, IFX, and ADA gave us excellent results in uveitis. Other newer biologics approved by the United States Food and Drug Administration for rheumatic diseases are emerging treatments for uveitis. These include the anti-CD20 inhibitors rituximab, the anti-TNF inhibitors certolizumab and golimumab, the IL-6 inhibitor tocilizumab, the IL-1 inhibitor anakinra, the cytotoxic T-lymphocyte antigen 4 inhibitor abatacept. Uveitis, a significant cause of ocular morbidity worldwide, is undergoing major changes as biologic therapies have entered into the field. We used PubMed and CrossRef (Google) search engine as the main source of information. In this review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging biological therapies in this context.

Case of Angiolymphoid Hyperplasia with Eosinophilia Associated with Anti-TNF Inhibitor

Case of Angiolymphoid Hyperplasia with Eosinophilia Associated with Anti-TNF Inhibitor

The effect of anti-TNF inhibitors on innate immune system in synovial tissues in rheumatoid arthritis patients

The effect of anti-TNF inhibitors on innate immune system in synovial tissues in rheumatoid arthritis patients

Clinical outcomes associated with switching or discontinuation of anti-TNF inhibitors for nonmedical reasons in psoriatic disease patients

Clinical outcomes associated with switching or discontinuation of anti-TNF inhibitors for nonmedical reasons in psoriatic disease patients

P-020 Clinical Outcomes Associated with Non-medical Switching or Discontinuation of Anti-TNF Inhibitors Among Patients with Inflammatory Bowel Disease

P-020 Clinical Outcomes Associated with Non-medical Switching or Discontinuation of Anti-TNF Inhibitors Among Patients with Inflammatory Bowel Disease

Sa1258 Comparison of Real-World Outcomes of Adalimumab (ADA) and Infliximab (IFX) for Patients With Ulcerative Colitis (UC) in the United States

Background: This study aimed to assess the comparative efficacy and safety of biologics in adult patients with moderately to severely active UC, stratified by prior exposure to antiTNF inhibitors. Methods: MEDLINE, Embase, The Cochrane Library, and ClinicalTrials.gov were systematically searched using a predefined search strategy, without language restrictions, for studies of approved biologics for UC (adalimumab, golimumab, infliximab, vedolizumab) published before February 2014. Two reviewers independently assessed studies for inclusion using a 2-step process; data on study design, patient characteristics, and outcomes were extracted from 8 RCTs (GEMINI I, ULTRA-1, ULTRA-2, ACT-1, ACT-2, PURSUIT-SC, PURSUIT-M, Suzuki et al. [2014] J Gasteronenterol, 49(2):283-94) that met the inclusion criteria and were suitable for network meta-analysis (NMA). The NMA was conducted for key endpoints at induction and maintenance, where data were available, in R and OpenBUGS using Bayesian fixed effects mixed treatment comparisons. Assumptions were made to account for differences in maintenance study design. Results: Seven studies were included in the analysis of induction treatment for anti-TNF-naive patients. All biologics were more effective than placebo in terms of response, remission, and mucosal healing, but rankograms suggested no significant differences between the included biologics. These results were consistent with recent reports (Danese et al. [2014] Ann Intern Med, 160(10):704-11). Five studies were included in the analysis of maintenance treatment for anti-TNF-naive patients. Vedolizumab every 8 weeks (Q8W) resulted in improved results versus comparators for all outcomes at week 52 and was associated with a significantly higher rate of durable clinical response than all comparators (Table 1). In patients who had previously received anti-TNFs, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were observed between the 2 biologics. During maintenance treatment, vedolizumab resulted in improved rates of durable response and remission and significantly improved rates of mucosal healing compared with adalimumab (Table 1). Conclusion: This study adds to the current understanding of the comparative efficacy and safety of biologic treatment for UC, encompassing outcomes and populations not included in previous studies. All biologic treatments are effective in the treatment of UC, with vedolizumab demonstrating benefits compared with all comparators irrespective of prior anti-TNF exposure in the maintenance setting.