anti-TNF Agents In Patients Research Articles

Mo1873 - Efficacy of Infliximab after Failure of Subcutaneous Antitnf Agent in Patients with Ulcerative Colitis: A Multicenter Study

Mo1873 - Efficacy of Infliximab after Failure of Subcutaneous Antitnf Agent in Patients with Ulcerative Colitis: A Multicenter Study

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.

Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.

We sought to analyze whether response to a second-line biologic varies depending on the reason for discontinuation of the primary anti-TNF agent (primary non-response [PNR], secondary loss of response [LOR] after initial response, or intolerance), through a systematic review and meta-analysis. Through a systematic search through May 31, 2017, we identified eight randomized controlled trials [RCTs] of biologics in patients with IBD with prior exposure to anti-TNF agents, that stratified response to second-line therapy by reason for discontinuing primary anti-TNF therapy [PNR vs. LOR vs. intolerance]. We estimated relative risk [RR] (and 95% confidence interval [CI]) of achieving clinical remission in patients with PNR as compared with patients with LOR, and intolerance, through random effects meta-analysis. As compared with patients who discontinued prior anti-TNF due to intolerance, patients with prior PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76 [0.61-0.96]). As compared with patients who discontinued prior anti-TNF due to LOR, patients with prior PNR were 27% less likely to achieve remission with induction therapy with second-line biologics (RR,0.73 [0.56-0.97]), particularly to ustekinumab (RR,0.64 [0.52-0.80]). There was no difference in response to vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85-1.58]). Patients with PNR to anti-TNF agents are less likely to respond to second-line non-TNF biologics, as compared with patients who discontinued therapy due to secondary LOR or intolerance. This may be attributed to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in patients with PNR.

P154 PRIMARY NON-RESPONSE TO TUMOR NECROSIS FACTOR ANTAGONISTS IS ASSOCIATED WITH INFERIOR RESPONSE TO SECOND-LINE BIOLOGICS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

We sought to analyze whether response to second-line biologic varies depending on reason for discontinuation of primary anti-TNF agent (primary non-response [PNR], secondary loss of response [LOR] after initial response, or intolerance), through a systematic review and meta-analysis. Through a systematic search through May 31, 2017, we identified 8 randomized controlled trials (RCTs) of biologics in patients with IBD with prior exposure to anti-TNF agents, that stratified response to second-line therapy by reason for discontinuing primary anti-TNF therapy (PNR vs. LOR vs. intolerance). We estimated relative risk (RR) [and 95% confidence interval (CI)] of achieving clinical remission in patients with PNR as compared to patients with LOR, and intolerance, through random effects meta-analysis. As compared to patients who discontinued prior anti-TNF due to intolerance, patients with prior PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76 [0.61–0.96]) (Figure 1). As compared to patients who discontinued prior anti-TNF due to LOR, patients with prior PNR were 27% less likely to achieve remission with induction therapy with second-line biologics (RR,0.73 [0.56–0.97]), particularly to ustekinumab (RR,0.64 [0.52–0.80]) (Figure 2). There was no difference in response to vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85–1.58]). Patients with PNR to anti-TNF agents are less likely to respond to second-line biologics, as compared to patients who discontinued therapy due to secondary LOR or intolerance. This may be attributed to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in patients with PNR.

P369 Efficacy of infliximab after failure of subcutaneous anti-TNF agents in patients with ulcerative colitis: A multicentre study

P369 Efficacy of infliximab after failure of subcutaneous anti-TNF agents in patients with ulcerative colitis: A multicentre study

Paradoxical Psoriasis Secondary to Anti-TNF Agents in Patients With Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study

Introduction: Anti-tumor necrosis factor (anti-TNF) agents have proven to be highly effective in the management of inflammatory bowel disease (IBD). However, there are growing reports on dermatologic adverse effects including paradoxical psoriasis secondary to anti-TNF agents. Methods: A cross sectional nationwide population study was performed by using the Korea National Health Insurance Claim Data. A total of 42,165 patients with IBD consisting of ulcerative colitis (UC) (n=29,434) and Crohn's disease (CD) (n=12,731) were identified between 2009 and 2013. After excluding those who had coexisting any psoriasiform diseases during the one-year washout period of 2009, 1,631 patients who were treated with any anti-TNFs more than 6 months (the anti-TNF therapy group), and 8,057 matched controls who had never taken anti-TNFs (the non anti-TNF group) were established to compare incidences of psoriasis, psoriatic arthritis, and palmoplantar pustulosis (PPP) between 2010 and 2013. Results: Incidence of psoriasis was significantly higher in the anti-TNF therapy group (1.90%, 31/1,631) compared to the non anti-TNF group (0.79%, 64/8,057) (adjusted odds ratio [aOR] 2.531, 95% confidence interval [CI] 1.611- 3.896; p <.001). Psoriatic arthritis (aOR 1.450, 95% CI 0.689-2.831) and PPP (aOR 4.885, 95% CI 1.579-14.314) also showed higher incidence rates in the anti-TNF therapy group, respectively. In subgroup analyses, aORs for psoriasis by IBD subtype were 1.832 (95% CI 0.587-5.098) in UC and 2.656 (95% CI 1.603-4.294) in CD. aORs for psoriasis according to age groups were 3.584 (95% CI 1.190 to 9.925) under 20 years old, 2.621 (95% CI 1.502 to 4.448) between 21 to 39, and 1.574 (95% CI 0.420 to 4.735) aged 40 and over, which implies younger IBD patients have a higher risk of paradoxical psoriasis secondary to anti-TNF agents. Conclusion: The risk of psoriasis is increased by anti-TNF agents in patients with IBD, and especially in younger patients.

Clinical Outcomes of Golimumab as First, Second or Third Anti-TNF Agent in Patients with Moderate-to-Severe Ulcerative Colitis.

Golimumab efficacy data in ulcerative colitis (UC) are limited to anti-tumor necrosis factor α (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6-73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7-39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6-18), 60 patients (42%, 95% confidence interval 34-51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF-naive patients had better outcomes, golimumab was also effective in anti-TNF-experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe.

P-087 YI Improvement of Anxiety and Depression Rates After 1 Year Treatment with Anti-TNF Agents in Patients with Inflammatory Bowel Disease

P-087 YI Improvement of Anxiety and Depression Rates After 1 Year Treatment with Anti-TNF Agents in Patients with Inflammatory Bowel Disease

Management of primary and secondary central nervous system vasculitis.

This article summarizes the current evidence on the management of primary and secondary central nervous system (CNS) vasculitis. Two recent retrospective cohort studies have described the treatment and outcomes of patients with adult primary central nervous system vasculitis (PCNSV). Although the majority of the patients (>60%) responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide (CYC) and tended to improve during the follow-up period, an overall increased mortality was observed. The treatment response and the outcomes appeared primarily related to the size of the vessels involved in the inflammatory process. The involvement of small cortical/leptomeningeal vessels was associated with a more benign course, whereas the involvement of larger/proximal cerebral vessels was related to a less favorable prognosis and identified cases that should be treated more aggressively. Glucocorticoids combined with CYC are the mainstay of therapy for secondary CNS vasculitis. Observational studies have documented the efficacy of rituximab as induction therapy in patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) and CNS disease, while the role of antitumor necrosis factor (TNF) agents is more controversial. Case series have demonstrated the efficacy of anti-TNF agents in patients with neuro-Behçet's disease. Tocilizumab may also be effective in this condition. Recognition of findings at diagnosis that predict the course or outcomes of PCNSV may serve as guide for therapy. Biological agents may provide benefit to difficult-to-treat patients with CNS involvement secondary to AAV and Behçet's disease.

Anti-TNF agents in patients with inflammatory bowel disease and malignant melanoma--challenges in management.

The inflammatory bowel diseases (IBD) are chronic immune-mediated inflammatory diseases of the gut that occur in genetically predisposed individuals exposed to environmental triggers. Several immunosuppressive agents have been successfully used for induction and maintenance treatment in inflammatory bowel disease. These include steroids, thiopurines, methotrexate, anti-tumor necrosis factor (anti-TNF) alpha agents, anti-alpha 4 integrins, and anti-IL-12/23 agent to name a few. There are also limited data on novel approaches including thalidomide and stem cell transplant. In spite of the significant successes associated with these agents, numerous malignancies have been associated with their use. Lymphomas including hepatosplenic T cell lymphomas, non-melanoma skin cancers and, more recently, melanoma have been described, specifically with anti-TNF. We reviewed the available published literature on melanoma in IBD, melanoma associated with anti-TNF, and the data on other treatment options in patients with IBD. In addition, we also reviewed the limited data on the gut specific integrin-vedolizumab. This may provide an additional option in the management of the subset of patients with IBD and melanoma. Options for treatment of IBD should be based on the stage of melanoma, control of IBD, and patient preferences. It should involve shared decision-making and close interdisciplinary follow-up between the IBD physician and the dermatologist, preferably with expertise in the management of melanoma. Treatment choices in patients with IBD and melanoma are challenging. There is very limited data providing guidance in this subset of patients. As such, treatment and follow-up should be individualized, extensively discussed with patients and their families as appropriate, and done in conjunction with a close follow-up by gastroenterologist and dermatologist.

Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients

ObjectiveTo report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). MethodsWe performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28–40) years]. ResultsOverall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12–0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7–36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. ConclusionAnti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy. We performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4-14 and 24-30 and remission at weeks 24-30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents. Overall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI, 0.79-1.48), maintaining a response (OR, 1.53; 95% CI, 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68-1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.) On the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated.

Sa1228 Predictors of Relapse Following Withdrawal of Anti-TNF Agents in Patients With Crohn's Disease in Remission - A Systematic Review and Meta-Analysis

Sa1228 Predictors of Relapse Following Withdrawal of Anti-TNF Agents in Patients With Crohn's Disease in Remission - A Systematic Review and Meta-Analysis

P362. Agalactosyl IgG predicts therapeutic effect of anti-TNF agents in patients with Crohn's Disease

P362. Agalactosyl IgG predicts therapeutic effect of anti-TNF agents in patients with Crohn's Disease

OP026. Post-operative use of anti-TNF agents in patients with Crohn's disease and risk of re-operation - a nationwide cohort study

OP026. Post-operative use of anti-TNF agents in patients with Crohn's disease and risk of re-operation - a nationwide cohort study

Exploring the clinical benefit with intra-articular injections of anti-TNF agent in patients with rheumatoid arthritis

Objective To observe the efficacy of intra-articular(IA)blockade of TNF-α by 3 etanercept injections in patients with rheumatoid arthritis(RA). Methods Eighteen moderate activity RA patients with resistant knee synovitis underwent three monthly IA injection of etanercept(25mg). The primary outcomes were visual analogue scale of target knee general health(VAS- TKGH) and VAS target knee Pain Score, and we also collected diameter of target knee joint, VAS fatigue Score, Health Assessment Questionnaire(HAQ), the 28-joint based disease activity score(DAS28)and joint fluid volume, which were all assessed at baseline and every four weeks after IA injection. Results All those 18 patients completed the treatment with the average disease duration of was(84.7± 54.1)months. After each IA injection, VAS- TKGH was significantly improved than baseline(P= 0.03,0.02, 0.02). and VAS target knee pain score was also significantly improved than baseline(P= 0.03,0.00,0.00). After 3rd IA injection,VAS- TKGH was further reduced compared with those after 1st and 2nd IA injection(P = 0.02,0.03);while, VAS target knee pain score was further reduced after 3rd IA injection(P= 0.00). Knee joint diameter, VAS fatigue score, HAQ and DAS 28 were significantly lower after 1st IA injection than baseline(P= 0.03,0.02,0.03). After 2nd IA injection, VAS fatigue score,HAQ,and DAS28 were significantly further improved compared to treatment once(P= 0.00,0.02,0.02);after 3rd IA injection,HAQ and DAS28 were further improved compared to those after 2nd IA injection(P= 0.01,0.02). Joint fluid volume was significantly decreased after 2nd IA injection(P= 0.01). Conclusion The tailor approach of intra- articular injections of anti- TNF agent might benefit RA patients who had resistant synovitis, and the side effect was rare. However, the sample was small and further observation is needed. Key words: Arthritis, rheumatoid; Repeators, tumor necrosis factor, type Ⅱ

P-069 Can PET CT Scans Be Used as a Predictor of Response to Treatment With Anti-TNF Agents in Patients With Crohn’s Disease?

Up to a third of patients with Crohn’s disease treated with Anti-TNF therapies are primary non-responders. Primary nonresponse may, in part, be due to stricturing disease with scarring rather than inflammation as the underlying pathology. Currently, the only way to identify primary nonresponders is to observe a lack of clinical and endoscopic response after repeated exposure to the medication. FDG-PET CT scans are a reliable tool to detect inflammation in the small bowel and may identify patients who are more likely to obtain benefit with Anti-TNF therapy. Our AIM was to determine whether low dose FDG-PET CT scan performed prior to first Anti-TNF exposure could identify patients likely to be responders at 12 weeks after Anti-TNF administration. Consecutive patients with small bowel Crohn’s disease who require therapy with Anti-TNF agents were recruited for the study. Information on disease information and disease activity were collected at the screening visit. An FDG-PET was performed and the maximum standardized uptake value (SUVmax) was calculated for each patient. The treating physician was blinded to the results. Patients were initiated on Anti-TNF therapy and re-evaluated for clinical response at week 12. Five consecutive patients with known small bowel Crohn’s disease with a clinical indication for treatment with anti-TNF therapy were recruited for the study (Table 1). All patients underwent FDG-PET CT scan and were exposed to infliximab. Three of 5 patients completed infliximab loading (1 lost to follow up, 1 required surgery). Two of 5 patients were identified as primary nonresponders at 12 weeks, but they were not associated with low SUVmax (Table 2). The SUVmax ranged from 5.2 to 13.4 (Table 1–2). There was not a statistically significant association between response to AntiTNF and treatment on SUVmax pretreatment. In this pilot study of patients with small bowel Crohn’s disease, FDG- PET CT scans did identify variable degrees of inflammation in the small bowel. Alternatives to SUVmax may be necessary to identify patients with small bowel inflammation that may be responsive to Anti-TNF therapy.

A Pilot Study of Positron Emission Tomography: Computed Tomography Scans as Predictors of Non-response to Treatment With Anti-TNF Agents in Patients With Small Bowel Crohn’s Disease

A Pilot Study of Positron Emission Tomography: Computed Tomography Scans as Predictors of Non-response to Treatment With Anti-TNF Agents in Patients With Small Bowel Crohn’s Disease

Treatment of Refractory Psoriasis with Ustekinumab in an HIV-Positive Patient: A Case Presentation and Review of the Biologic Literature

Here we describe a case of a 39-year-old male with HIV and a 20-year history of generalized plaque psoriasis and psoriatic arthritis. The patient had been refractory to all treatments until initiating ustekinumab, the monoclonal antibody against IL-12/23. While using ustekinumab, the patient's CD4 T-cell count and HIV viral load have remained stable. Due to the questions surrounding the use of biologics in HIV-positive patients, we review the successful use of anti-TNF agents in patients with chronic HIV infection as well as the single other reported case of ustekinumab's use in an HIV-positive patient. We therefore begin to build the case for ustekinumab as an alternative biologic therapy for the HIV-infected psoriasis patient.

Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous anti-TNF agents in patients with rheumatoid arthritis?

The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.