Anti-tumor Necrosis Factor-α Therapy Research Articles

Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO)

Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.

Frequency and clonality of peripheral γδ T cells in psoriasis patients receiving anti-tumour necrosis factor-α therapy.

Hepatosplenic γδ T cell lymphoma (HSTCL) has been observed in patients with Crohn's disease (CD) who received anti-tumour necrosis factor (TNF)-α agents and thiopurines, but only one case was reported in a psoriasis patient worldwide. This difference could be due to differences in either the nature of the inflammatory diseases or in the use of immunomodulators. We investigated the impact of anti-TNF-α agents on the level and repertoire of γδ T cells in peripheral blood from psoriasis patients. Forty-five men and 10 women who were treated with anti-TNF-α agents for psoriasis were monitored for a median 11 months for the level and clonality of γδ T cells via flow cytometry and polymerase chain reaction (PCR) analysis of T cell receptor gamma (TCR-γ) gene rearrangements. Seventeen men had a repeated analysis within 48 h of the infliximab infusion to reveal a possible expansion of γδ T cells, as observed previously in CD patients. Ten psoriasis patients who were never exposed to biologicals and 20 healthy individuals served as controls. In the majority of psoriasis patients, the level and clonal pattern of γδ T cells was remarkably stable during infliximab treatment. A single male patient repeatedly experienced a significant increase in the level of γδ T cells after infliximab infusions. A monoclonal γδ T cell repertoire in a polyclonal background tended to be more frequent in anti-TNF-α-treated patients than naive patients, suggesting that anti-TNF-α therapy may promote the clonal selection of γδ T cells in psoriasis patients.

Changes in Vitamin D-Related Mineral Metabolism After Induction With Anti-Tumor Necrosis Factor-α Therapy in Crohn's Disease

Preclinical studies suggest that TNF-α suppresses PTH synthesis, inhibits renal 1α-hydroxylase activity, and impairs fibroblast growth factor 23 (FGF23) degradation. The impact of inflammation on vitamin D and mineral metabolism has not been well-characterized in Crohn's disease (CD). The objective of the study was to assess short-term changes in vitamin D-related mineral metabolism in CD after anti-TNF-α induction therapy. Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-α therapy and 10 weeks later. Indices of clinical disease activity and serum concentrations of vitamin D metabolites, vitamin D-binding protein (DBP), calcium, PTH, FGF23, IL-6, and TNF-α were measured at each visit. A multivariable generalized estimating equation (GEE) regression analysis was used to examine the correlates of PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations at each visit. After anti-TNF-α therapy, cytokines and inflammatory markers [IL-6, TNF-α, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] concentrations decreased (all P < .0001), and PTH and 1,25(OH)2D concentrations increased (median 21 vs 30 pg/mL, P < .0001, and median 41.7 vs 48.1 pg/mL, P = .014, respectively). Levels of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D, DBP, and FGF23 did not change. In GEE analyses, higher IL-6, TNF-α, ESR, and CRP were associated with lower PTH concentrations (all P < .001), adjusted for corrected calcium and 25(OH)D levels. Higher PTH was associated with higher 1,25(OH)2D concentrations (P < .001) at each visit, independent of 25(OH)D concentrations. Higher levels of all inflammatory markers were associated with lower 1,25(OH)2D concentrations (all P < .05). However, when PTH was added to these models, the inflammatory markers (with the exception of CRP) were no longer significantly associated with 1,25(OH)2D. Greater inflammation was associated with lower PTH and 1,25(OH)2D concentrations. After anti-TNF-α induction, PTH and 1,25(OH)2D concentrations increased without concomitant changes in 25(OH)D and FGF23, consistent with effects of inflammation on PTH and thereby renal conversion of 25(OH)D to 1,25(OH)2D.

The long-term outcome of anti-tumor necrosis factor-α therapy related to fecal calprotectin values during induction therapy in pediatric inflammatory bowel disease

Objective. Monitoring fecal calprotectin (FC) could assist in the assessment of the therapeutic response of inflammatory bowel disease (IBD). There are few studies on long-term prognosis related to the FC value response to infliximab induction therapy, thus providing the aim of this study on pediatric patients. Methods. FC levels were measured during the induction and maintenance phase of infliximab therapy (5 mg/kg) in 76 pediatric IBD patients introduced to maintenance therapy. The long-term outcomes and clinical disease activity were retrospectively related to the FC response to induction. Results. The median pretreatment FC level of 817 μg/g stool (range <5–24,000) declined to 372 μg/g (range 5–2430) by week 6, with a low level (<100 μg/g) in 35% (pooled comparable data for ulcerative colitis and Crohn’s). Clinical activity indices showed remission in 59% (pediatric Crohn's disease activity index: <10, n = 33; pediatric ulcerative colitis activity index: <10 n = 12). In 49 patients (64%), infliximab therapy was discontinued (inadequate effect/surgery = 27; remission/bridging to azathioprine = 12; adverse effect = 6; antibodies to infliximab n = 4) during the study period with a median follow up of 1.1 years (interquartile range [IQR]: 0.71–4.4). Those who discontinued the therapy within the first year due to an inadequate effect had higher median FC level during induction than the other patients (median 633 µg/g, IQR: 197–819 and median 219 µg/g, IQR: 71–508, respectively; p < 0.025) and were less frequently in clinical remission at week 6 (p < 0.01). Conclusions. The long-term prognosis of infliximab therapy is related to the response to induction therapy in pediatric IBD and reflected in low FC values between weeks 2 and 6 and clinical remission.

Crohn's disease and growth deficiency in children and adolescents.

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn's disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using "pediatric inflammatory bowel disease", "pediatric Crohn's disease", "linear growth", "pubertal growth", "bone health", and "vitamin D" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients' growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a "top-down" approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients' nutritional status.

Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-α Therapy

PurposeAnti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea.Materials and MethodsWe retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected.ResultsA total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn's disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results.ConclusionSerious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.

Is universal screening for hepatitis C infection prior to commencing antitumour necrosis factor-α therapy necessary?

Screening for hepatitis C virus (HCV) prior to the commencement of antitumour necrosis factor (anti-TNF)-α therapies for dermatological disease is recommended for all patients. To determine the incidence of HCV infection among dermatology patients who were screened for HCV infection prior to commencing anti-TNF-α therapies. We reviewed the HCV infection status of all patients attending our dermatology department who had been tested for evidence of HCV infection between January 2005 and November 2012. We identified patients who had been tested as part of routine screening prior to commencing anti-TNF-α therapy using dermatology departmental records. In total, 215 patients were screened for HCV infection prior to commencing anti-TNF-α therapies. Among this group, 143 patients (66·5%) were male and 72 (33·5%) were female. None of these patients tested positive for active HCV infection. One patient tested positive for HCV antibody with negative HCV antigen and HCV RNA. This indicated previous HCV infection that had cleared. This patient had abnormal liver function tests and a history of alcohol excess. There were no cases of active HCV infection diagnosed through pretreatment anti-TNF-α screening in our department, which is located in a low-prevalence area for HCV infection. In view of the lack of evidence of harm associated with anti-TNF-α use in HCV-infected patients, we propose that screening for HCV infection in low-prevalence areas should be targeted to those with pre-existing risk factors. This is consistent with current guidelines from the Royal College of General Practitioners. Targeted screening rather than universal screening may be a safe and cost-effective option among patients being evaluated for anti-TNF-α therapies.

Recalcitrant psoriasis responding to new bilogic drug: Ustekinumab

Recalcitrant psoriasis responding to new bilogic drug: Ustekinumab

Operative Strategy Modifies Risk of Pouch-related Outcomes in Patients With Ulcerative Colitis on Preoperative Anti-Tumor Necrosis Factor-α Therapy

Whether preoperative biological therapy increases postoperative complications after restorative proctocolectomy remains controversial. This study aims to evaluate the influence of preoperative use of biologics on outcomes after restorative proctocolectomy and to assess whether a staged approach modifies any negative influence of these medications. The study was conducted at a single tertiary institution. Patients who were operated on for medically refractory ulcerative or indeterminate colitis were identified and classified by initial surgery, whether subtotal colectomy or total proctocolectomy, then categorized into biologics user and nonuser groups. Demographics, perioperative data, postoperative complications, pouch function, and quality of life were collected. Cumulative 1-year complication rates were estimated by using the Kaplan-Meier curve, and independent predictors for infectious complications were identified by using Cox proportional hazards regression models. From 2006 to 2010, 407 and 181 patients underwent initial subtotal colectomy with end ileostomy or total proctocolectomy with IPAA. For the 181 patients who underwent total proctocolectomy straightaway, pre- and perioperative data were comparable for biologics users (n = 25) and nonusers (n = 156). Cumulative 1-year pelvic sepsis rate was significantly greater in patients on biologics (32% vs 16%, p = 0.012). Multivariate analysis demonstrated that preoperative anti-tumor necrosis factor therapy (HR, 2.62; p = 0.027) was an independent risk factor for postoperative pelvic sepsis after total proctocolectomy. After subtotal colectomy, no differences occurred in both 30-day and cumulative 1-year postoperative complications between biologics users (n = 142) and nonusers (n = 265). Outcomes were also similar when biologics users (n = 88) and nonusers (n = 164) underwent subsequent completion proctectomy with ileal pouch creation after initial colectomy. The retrospective nature of this study and physician's preference were limitations. Preoperative exposure to biologics is associated with an increased risk of pelvic sepsis after total proctocolectomy with IPAA. This risk is mitigated by the performance of an initial subtotal colectomy.

Costs of adalimumab versus infliximab as first-line biological therapy for luminal Crohn's disease

Background and aimsRandomised controlled trials demonstrate that the anti-tumour necrosis factor-α (anti-TNFα) therapies infliximab and adalimumab are effective in inducing remission and preventing relapse of Crohn's disease (CD). As few studies have compared costs and efficacy of these two drugs directly, we examined this issue. MethodsData were collected for patients receiving either drug as first-line anti-TNFα for CD. Patients were matched as closely as possible on age, gender, weight, height, and date of commencement of therapy. Response to induction therapy was assessed at 12weeks, and sustained clinical benefit at last point of follow-up. Resource data were collected for all patients until study end, with National Health Services reference costs applied to calculate the total cost per patient with adalimumab compared with infliximab. ResultsThirty-six patients had been treated with adalimumab as first-line anti-TNFα since 2010. We matched an identical number of infliximab patients. Demographic data were similar between the two groups. Costs were significantly lower with adalimumab (£6692.95 less per patient (95% confidence interval £1816.61–£11569.29)), which was largely driven by the drug costs and drug administration costs associated with infliximab. Twenty-nine (80.6%) patients responded to induction therapy with both drugs, and 22 (61.1%) achieved glucocorticosteroid-free sustained clinical benefit with either drug at last point of follow-up. ConclusionsCosts of infliximab used as first-line anti-TNFα therapy are greater, which may have implications for selection. Clinical outcomes appeared comparable, although power to detect a statistically significant difference would be limited.

Changes in the level of serum microRNAs in patients with psoriasis after antitumour necrosis factor-α therapy

MicroRNAs (miRNAs) are endogenous, nonprotein-coding, regulatory RNAs with important roles in health and disease. miRNAs are present in the circulation in a stable form and their levels are altered in diseases. To determine whether antitumour necrosis factor (TNF)-α therapy affects serum miRNA levels in patients with psoriasis. Serum samples were obtained from healthy donors and from patients with chronic plaque psoriasis before and 12 weeks after the initiation of treatment with the TNF-inhibitor etanercept or methotrexate. miRNA expression profiling was utilized to identify miRNAs with altered serum level in psoriasis, as well as anti-TNF-α-regulated miRNAs in patients' sera. The expression of five miRNAs regulated by etanercept was measured by quantitative polymerase chain reaction (qPCR) in sera from patients and controls. Etanercept significantly suppressed a panel of 38 miRNAs, which were found to be predominantly immune-cell derived and which have been implicated in inflammation and autoimmunity. Validation by qPCR showed that serum levels of miR-106b, miR-26b, miR-142-3p, miR-223 and miR-126 were significantly downregulated by etanercept in responders (Psoriasis Area and Severity Index change > 50%). By contrast, methotrexate did not significantly affect the levels of these miRNAs. Serum levels of these miRNAs were not upregulated in patients with psoriasis compared with healthy controls. The level of four circulating miRNAs was significantly different (increased: miR-128a; decreased: let-7d, miR-142-3p, miR-181a) in psoriasis and healthy serum. The level of circulating miRNAs is altered in psoriasis. Anti-TNF-α therapy has a profound effect on the serum level of miRNAs; however, these are not related to disease severity. Our results suggest that changes in the miRNA level may reflect a previously unknown effect of anti-TNF-α therapy. Our results suggest the involvement of miRNAs in pathways affected by anti-TNF-α therapy and warrant further investigation of serum miRNAs as potential biomarkers for therapy response in psoriasis.

Mortality and Cancer in Pediatric-Onset Inflammatory Bowel Disease: A Population-Based Study

Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized. All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohn's disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fisher's exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios. A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12-16) and the median follow-up time was 11.5 years (7-15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5-3.0); P=0.27). After a median follow-up of 15 years (10-17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3-5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients). In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.

Response to Letter Regarding Article, “Anti–Tumor Necrosis Factor-α Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis”

We thank the authors for their interest in our study.1 They raise several relevant points, which we address below. We agree that further work is needed to ascertain the origin of 18F-fluoro-deoxyglucose (FDG) uptake in patients with rheumatoid arthritis. Although we cannot be certain, we feel that subclinical vasculitis is the most likely explanation for our findings for several reasons. First, we compared aortic FDG uptake in rheumatoid arthritis subjects with an atherosclerotic population with stable cardiovascular disease, matched for age. We were careful to exclude those rheumatoid arthritis subjects with established cardiovascular disease or diabetes mellitus. Even so, we found that the aortic FDG uptake …

Letter by Lensen et al Regarding Article, “Anti-Tumor Necrosis Factor-α Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis”

To the Editor : We read with interest the article by Maki-Petaja et al1 describing the effects of anti–tumor necrosis factor therapy on vascular inflammation in patients with rheumatoid arthritis. The suggestion of subclinical vasculitis as a contributor to cardiovascular complications is intriguing, but was it really vasculitis they saw, or atherosclerosis? First, the pattern of aortic 18F-fluorodeoxyglucose (18F-FDG) uptake does not suggest vasculitis. The focal rather than diffuse distribution of the lesions …

Bacterial endophthalmitis caused by an intraocular cilium in a patient under treatment with infliximab

BackgroundWe report a case of bacterial endophthalmitis caused by an intraocular cilium in a patient without any history of trauma or ocular surgery.FindingsA 32-year-old Caucasian male showed symptoms of orbital myositis and scleritis, with no intraocular inflammation in the right eye. The patient had been treated with infliximab for Crohn’s disease. Three weeks after initiation of oral prednisolone therapy, he developed bacterial endophthalmitis. During pars plana vitrectomy, a cilium in the massive vitreous opacity was found. A focal scleral necrosis was detected just outside where the cilium was intraoperatively observed. Vitreous culture showed the presence of Staphylococcus aureus.ConclusionsThe intraocular cilium seemed to be the aetiology of the endophthalmitis in this case, which suggests that anti-tumour necrosis factor-α therapy may play a role in the migration of cilia into the globe and the occurrence of endophthalmitis.

SAT0148 Does depression affect response to anti-tumour necrosis factor-α therapy in patients with rheumatoid arthritis (RA)? Results from the british society for rheumatology biologics register (BSRBR)

BackgroundDepression is widely reported in RA, with prevalence estimates at 14-46%. Several studies have suggested that RA patients with persistent depression have poorer response to anti-TNF therapy.ObjectivesTo investigate the effects...

Opportunistic Infections With Anti-Tumor Necrosis Factor-α Therapy in Inflammatory Bowel Disease: Meta-Analysis of Randomized Controlled Trials

Several anti-tumor necrosis factor-α (TNFα) antibodies have demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC). These drugs carry the theoretical risk of opportunistic infection, but no systematic review and meta-analysis has examined this issue specifically. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to November 2012). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD or UC comparing anti-TNFα therapy with placebo were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection, with a 95% confidence interval (CI). The number needed to harm (NNH) was estimated from the reciprocal of the risk difference from the meta-analysis. The search strategy identified 20,563 citations, 21 of which were eligible, reporting 22 separate RCTs with between 2 and 56 weeks of follow-up. In total, there were 39 (0.9%) opportunistic infections among 4,135 patients allocated to anti-TNFα therapy, compared with 9 (0.3%) among 2,919 assigned to placebo. Among patients receiving active therapy these included eight cases of Mycobacterium tuberculosis, eight cases of herpes simplex infection, six cases of oral or esophageal candidiasis, six cases of herpes zoster infection, two cases of varicella-zoster virus infection, two cases of cytomegalovirus or Epstein-Barr virus infection, and one case of Nocardia infection. The RR of developing an opportunistic infection was significantly higher with anti-TNFα therapy (2.05; 95% CI 1.10-3.85, NNH=500; 95% CI 200-1,567). The RR of tuberculosis infection was 2.52 (95% CI 0.62-10.21). Anti-TNF therapy doubles the risk of opportunistic infections in inflammatory bowel disease patients. This underlines the importance of adherence to guidelines for their prevention and management.

Risk Factors for Osteoporosis in Crohnʼs Disease

We analyzed the characteristics associated with increased risk of osteoporosis in patients with Crohn's disease in Malta. Eighty-three patients with histologically and endoscopically confirmed Crohn's disease underwent a DEXA bone density scan and their phenotypic characteristics were analyzed. There was a significant association between body mass index and bone mineral density (P = 0.004) and a significant difference in the T scores of patients according to age at diagnosis (Montreal Classification: P = 0.0006) with patients diagnosed <17 years (n = 13) having lower T scores than those diagnosed at older age groups (n = 70). There was a significant difference between the T scores of patients on infliximab (n = 33) and those not on biological therapy (n = 50, P = 0.0058). Patients with high cumulative corticosteroid doses (>10 mg/d for >3 mo, n = 18) had lower bone mineral densities than patients who received smaller corticosteroid doses (P = 0.013). There was however no significant difference in the T scores of patients according to disease location (P = 0.18), disease type (P = 0.64), gender (P = 0.30), and history of ileal resection (P = 0.68). There was also no significant correlation between disease duration and T scores (hip) (P = 0.61). Low body mass index, early disease onset, high corticosteroid doses and, anti-tumor necrosis factor α therapy are associated with increased risk of osteoporosis. Lower T scores in patients on infliximab occur as patients receiving this therapy have more severe inflammation, which is associated with elevated osteoclastogenic factors, rather than as a side-effect of the anti-tumor necrosis factor-α therapy.

Su1212 Incidence of Surgery and Associated Costs At 1 and 2 Years in Patients Newly Initiated to a Subcutaneous Anti-TNF for the Treatment of Crohn's Disease

BACKGROUNDCrohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. For patients with severe CD, uncontrolled inflammation can result in a high incidence of long-term complications, including surgery.[1] Anti-tumor necrosis factor-α (anti-TNF) therapy is indicated for patients with CD who have an inadequate response to conventional therapy. The aim of this analysis is to evaluate the incidence of CD-related surgery and the associated costs at 1 and 2 years in patients with CD prescribed an anti-TNF agent administered subcutaneously (adalimumab [ADA]) or certolizumab pegol [CZP]). METHODS OptumInsight's Clinformatics Data Mart, a database of administrative health claims from a large national health insurer, was used for the analysis. US patients were identified with a diagnosis of CD and receipt of an anti-TNF prescription of ADA or CZP from April 2008January 2012. Patients were eligible for inclusion in the analysis if they were aged ≥18 years with a diagnosis of CD, had not received anti-TNF therapy in the 6 months prior to first anti-TNF, and had 24 months' pharmacy and medical continuous enrollment in the database. The number of patients prescribed ADA or CZP who had surgery for CD during a 1-year or 2-year study period was evaluated. Average (mean) and median CD-specific costs (including CD-related medications, visits, and surgeries) and total costs (CD-specific plus all other associated costs [including visits and laboratory tests]) were also assessed. RESULTS There were 273 ADA patients and 75 CZP patients identified who met the inclusion criteria. No differences in the incidence of CD surgery during a 1and 2-year study period were observed for patients initiated on ADA or CZP (Table). Average (mean) CD-specific costs and total costs for patients initiated on ADA or CZP during a 1and 2-year study period are shown in the Table. Median CD-specific costs for patients initiated on ADA and CZP were $26,987 and $26,744 at 1 year and $52,928 and $45,292 at 2 years. Median total costs were $29,950 and $30,490 at 1 year and $59,329 and $50,432 at 2 years. CONCLUSIONS This analysis of a US claims database showed that over 1 and 2 years, the incidence of CD surgery was similar for patients prescribed ADA or CZP. The 2-year incidence of CD surgery with a subcutaneous anti-TNF (11%-12%) appears to be lower than that seen in the general CD population.[1] CD-specific and overall claims costs were similar for ADA or CZP at 1 year; at 2 years, costs were found to be slightly higher in the ADA treatment group. Limitations of this analysis were the inability to account for disease severity and the low number of patients with available claims at 2 years. REFERENCE 1. Peyrin-Biroulet L, et al. Am J Gastroenterol 2012;107:1693-701. Table

Evaluating the use of the interferon-γ response toMycobacterium tuberculosis-specific antigens in patients with psoriasis prior to antitumour necrosis factor-α therapy: a prospective head-to-head cross-sectional study

Background Targeted biological therapies have transformed the treatment of chronic inflammatory disease. However, reactivation of latent tuberculosis infection (LTBI) is a significant risk with the use of antitumour necrosis factor (anti‐TNF)‐α therapy and screening is mandatory prior to treatment. The tuberculin skin test (TST) may be difficult to interpret in patients with inflammatory disease or receiving immunosuppressive therapies. Objectives The aim of this study was to evaluate and compare the QuantiFERON®‐TB Gold In‐Tube (QFR) and T‐SPOT.TB (TSTB) interferon‐γ‐release assays (IGRA) against the TST in a cohort of patients commencing anti‐TNF‐α therapies for chronic inflammatory disease. Methods A prospective cross‐sectional study was undertaken at a London tertiary referral centre. Demographic data collected included TB risk factors. TST, QFR and TSTB were performed in all patients. Results Seventy patients with chronic plaque psoriasis were included in the study. Agreement between QFR and TSTB, excluding indeterminate results, was 89% (κ = 0·567), between QFR and TST 85% (κ = 0·313) and 81% (κ = 0·244) between TSTB and TST. There was no significant association with concomitant immunosuppression and either TST or IGRA results. Seven patients received chemoprophylaxis for LTBI diagnosed after clinical risk assessment together with positive TST and/or IGRA. Three patients had positive results in all three tests. Conclusions While there was moderate overall agreement between QFR and TSTB and fair correlation between TST, QFR and TSTB, there were a number of discordant results, suggesting that a three‐pronged approach using TST, QFR and TSTB may be of additional benefit.