Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

The effectiveness of the anti-tumor necrosis factor therapy infliximab in neuro-Behçet's disease: a systematic review and meta-analysis.

OBJECTIVE: To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease. METHODS: In this systematic review and meta-analysis, the research question was designed using the 'Population, Intervention, Comparator, and Outcomes' (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I2 statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence. RESULTS: Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I2 = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years. CONCLUSION: Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet's disease.

Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients With Crohn's Disease: A Pilot Study.

BACKGROUND: Early changes in bowel behavior during anti-tumor necrosis factor (anti-TNF) induction therapy in Crohn's disease (CD) are relatively unknown. We determined (1) the onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound and (2) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. METHODS: Consecutive ileal or ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. RESULTS: Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the nonresponse group (P = .003 and P = .011, respectively). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P < .001, P < .001, and P = .003, respectively) in the response group. Baseline SWE values (21.3 ± 8.7 kPa vs 15.3 ± 4.7 kPa; P = .022) and bowel wall thickness (8.5 ± 2.3 mm vs 6.9 ± 1.5 mm; P = .027) in the nonresponse group were significantly higher than in the response group. CONCLUSIONS: This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as 2 weeks after anti-tumor necrosis factor therapy in patients with Crohn's disease. Bowel ultrasound together with elasticity imaging could predict early response to anti-tumor necrosis factor therapy.

Heart failure as an adverse effect of infliximab for Crohn's disease: A case report and review of the literature.

BACKGROUND: Anti-tumor necrosis factor agents were the first biologic therapy approved for the management of Crohn's disease (CD). Heart failure (HF) is a rare but potential adverse effect of these medications. The objective of this report is to describe a patient with CD who developed HF after the use of infliximab. CASE SUMMARY: A 50-year-old woman with a history of hypertension and diabetes presented with abdominal pain, diarrhea, and weight loss. Colonoscopy and enterotomography showed ulcerations, areas of stenosis and dilation in the terminal ileum, and thickening of the intestinal wall. The patient underwent ileocolectomy and the surgical specimen confirmed the diagnosis of stenosing CD. The patient started infliximab and azathioprine treatment to prevent post-surgical recurrence. At 6 mo after initiating infliximab therapy, the patient complained of dyspnea, orthopnea, and paroxysmal nocturnal dyspnea that gradually worsened. Echocardiography revealed biventricular dysfunction, moderate cardiac insufficiency, an ejection fraction of 36%, and moderate pericardial effusion, consistent with HF. The cardiac disease was considered an infliximab adverse effect and the drug was discontinued. The patient received treatment with diuretics for HF and showed improvement of symptoms and cardiac function. Currently, the patient is using anti-interleukin for CD and is asymptomatic. CONCLUSION: This reported case supports the need to investigate risk factors for HF in inflammatory bowel disease patients and to consider the risk-benefit of introducing infliximab therapy in such patients presenting with HF risk factors.

Risk of hepatitis B reactivation in patients receiving anti-tumor necrosis factor-α therapy.

OBJECTIVE: The purpose of this study was to determine hepatitis B virus (HBV) screening rates in patients receiving anti-tumor necrosis factor (TNF)-α therapy and the frequency of HBV reactivation in patients with resolved hepatitis B virus infection (hepatitis B surface antigen [HBsAg] negative, hepatitis B core antibody [Anti-HBc] positive). PATIENTS AND METHODS: Data from 1834 patients who underwent anti-TNF-α therapy in the Rheumatology, Gastroenterology and Dermatology Departments of our hospital between 2010 and 2020 were retrospectively analyzed. Within 6 months before the initial anti-TNF-α therapy, performing a HBsAg and/or anti-HBc test is defined as HBV screening. HBV reactivation is defined as the presence of detectable serum HBV DNA or HBsAg seroconversion from negative to positive. RESULTS: The overall HBV screening rate was 82.3% before starting anti-TNF-α therapy. There was an increasing trend in HBV screening rates during the years analyzed (64% in 2010, 87.4% in 2019) (P < .001). Before anti-TNF-α therapy was initiated, 272 patients were HBsAg negative and anti-HBc positive. Among these patients, HBV reactivation did not occur in 31 patients who received antiviral prophylaxis, whereas HBV reactivation occurred in only 1 (0.4%) of the 241 patients who did not receive antiviral prophylaxis. CONCLUSION: Hepatitis B virus screening rates prior to starting anti-TNF-α therapy were relatively high, and its trend was increased by year. HBV reactivation because of anti-TNF-α use rarely occurred in patients with resolved HBV infection. Further studies are needed on whether routine anti-HBc screening and/or HBV DNA follow-up are necessary in these patients aside from HBsAg.

Safety and Efficacy of Intravenous Golimumab in Adults with Ankylosing Spondylitis: Results through 1 Year of the GO-ALIVE Study.

OBJECTIVE: Evaluate safety and efficacy of intravenous (IV) golimumab (GOL) in patients with active ankylosing spondylitis (AS) through 1 year. METHODS: A total of 208 patients were randomized to IV infusions of GOL 2 mg/kg (n = 105) at weeks 0, 4, and every 8 weeks thereafter or placebo (n = 103) at weeks 0, 4, and 12, then crossover to GOL at weeks 16, 20, and every 8 weeks thereafter through Week 52. Efficacy was assessed using the Assessment of Spondyloarthritis international Society (ASAS) criteria, the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Bath Ankylosing Spondylitis Functional Index (BASFI). Health-related quality of life was assessed using the AS Quality of Life (ASQoL) index. Efficacy and safety were monitored through Week 52 and Week 60, respectively. RESULTS: The primary endpoint (ASAS20) and all controlled endpoints at Week 16 were achieved. At Week 52, 69.5% and 65.0% of patients in the GOL group and placebo crossover group, respectively, achieved an ASAS20; 56.2% and 51.5% achieved an ASAS40; 56.2% and 55.3% achieved a BASDAI50; 24.8% and 24.3% achieved ASAS partial remission; and 25.7% and 26.2% met ASDAS inactive disease criteria (all last observation carried forward). Mean changes from baseline to Week 52 in BASFI and ASQoL scores were similar between the GOL group and the placebo crossover group (BASFI: -2.7 and -2.6; ASQoL: -5.5 and -5.4). Through Week 60, 55.4% of all GOL-treated patients had ≥ 1 adverse events (AE); 3.4% had ≥ 1 serious AE. CONCLUSION: Efficacy was maintained through 1 year with IV GOL 2 mg/kg among patients with active AS. AE were consistent with the known safety profile of GOL.

Tuberculosis screening prior to anti-tumor necrosis factor therapy among patients with immune-mediated inflammatory diseases in Japan: a longitudinal study using a large-scale health insurance claims database.

AIM: Tuberculosis screening is recommended for patients with immune-mediated inflammatory diseases (IMIDs) prior to anti-tumor necrosis factor (TNF) therapy. However, adherence to the recommended practice is unknown in the current clinical setting in Japan. METHODS: We used a large-scale health insurance claims database in Japan to conduct a longitudinal observational study. Of more than two million beneficiaries in the database between 2013 and 2014, we enrolled those with IMIDs aged 15-69 years who had initiated anti-TNF therapy. We defined tuberculosis screening primarily as tuberculin skin test and/or interferon-gamma release assay (TST/IGRA) within 2 months before commencing anti-TNF therapy. We analyzed the proportions of the patients who had undergone tuberculosis screening and the associations with primary disease, type of anti-TNF agent, methotrexate prescription prior to anti-TNF therapy, and treatment for latent tuberculosis infection (LTBI). RESULTS: Of 385 patients presumed to have initiated anti-TNF therapy, 252 (66%) had undergone tuberculosis screening by TST/IGRA (22% TST, 56% IGRA, and 12% both TST and IGRA), and 231 (60%) had undergone TST/IGRA and radiography. Patients with psoriasis tended to be more likely to undergo tuberculosis screening than those with other diseases; however, this association was not statistically significant. Treatment for LTBI was provided to 43 (11%) patients; 123 (32%) received neither TST/IGRA nor LTBI treatment. CONCLUSIONS: Tuberculosis screening was often not performed prior to anti-TNF therapy despite the guidelines' recommendations; thus, patients could be put at unnecessary risk of reactivation of tuberculosis.

Transcriptional profiling of leukocytes from rheumatoid arthritis patients before and after anti-tumor necrosis factor therapy: A comparison of anti-nuclear antibody positive and negative subsets.

Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy. Serum was assayed for ANAs over time. Total cellular RNA was extracted from PBMCs and assessed using Illumina arrays. Gene expression profiles were examined for alterations in key effector pathways. After 3 or more months on TNFi, 6 patients converted to ANA-positivity. Analysis of transcripts from patients with RA who converted to ANA-positivity after 3 months on TNFi identified complex gene expression profiles that reflected a reduction in cell adhesion, cell stress and lipid metabolism transcripts. In summary, unique transcriptional profiles in PBMCs from patients with RA were observed after TNFi therapy. This pilot study suggests that transcriptional profiling is a precise method of measuring the impact of TNFi therapies and reveals novel pathways that likely influence the immune response.

Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy.

AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory (TNF, IL-1ß, IL-6), immuno-regulatory (IL-10), Th1 (IL-12, IFNγ) and Th2 (IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS. RESULTS: Prior to anti-TNF therapy, responders and non-responders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders (P < 0.05). Following TLR stimulation, non-responders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls (P < 0.01) and diminished TNF (P < 0.001) and IL-1ß (P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells (pDCs) (P < 0.01) but increased number of CD4+ regulatory T cells (Tregs) (P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2, -4 and -7 activation (P < 0.001). CONCLUSION: Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.

Does Concomitant Methotrexate with Adalimumab Influence Treatment Outcomes in Patients with Psoriatic Arthritis? Data from a Large Observational Study.

OBJECTIVE: To examine the influence of concomitant methotrexate (MTX) with adalimumab (ADA) on outcomes in patients with psoriatic arthritis (PsA) using data from an observational study of ADA. METHODS: Data from a German noninterventional study of patients with PsA starting treatment with ADA were analyzed retrospectively for effects of concomitant MTX on key outcomes, including Disease Activity Score-28 joints, tender and swollen joint counts, skin assessments, and safety. Patients were categorized into those with symptoms of axial involvement and those with no symptoms of axial involvement as judged by the examining clinician. RESULTS: A total of 1455 patients met the study criteria, 296 with axial involvement (ADA monotherapy = 165; plus MTX = 131) and 1159 with no axial involvement (ADA monotherapy = 658; plus MTX = 501). ADA, alone or combined with MTX, resulted in strong and comparable reductions in disease activity measures in patients with and those without axial disease over 24 months of therapy. In multiple regression analyses, concomitant MTX did not affect joint or skin outcomes in either the group with axial manifestations or the group without axial disease. Neither adverse event rates nor withdrawal rates were significantly influenced by concomitant MTX. CONCLUSION: ADA is an effective treatment option for patients with PsA with or without axial involvement. Compared with ADA monotherapy, the use of concomitant MTX with ADA does not improve articular or skin outcomes in patients with PsA regardless of axial symptoms. TRIAL REGISTRATION: Clinicaltrials.gov NCT01111240.

Reduction of Inflammation Drives Lipid Changes in Ankylosing Spondylitis.

OBJECTIVE: To investigate the effects of changing inflammation on lipid levels in ankylosing spondylitis. METHODS: In a cohort of 230 patients, lipid levels were measured at baseline and after 52 weeks of treatment with tumor necrosis factor-α-blocking agents (anti-TNF). RESULTS: Total cholesterol (TC; +4.6%), low-density lipoprotein cholesterol (+4.3%), and high-density lipoprotein cholesterol (HDL-C; +3.7%) increased upon treatment. Changes were most evident in patients with substantial reduction in inflammatory levels (TC +8.2% vs +1.6% and HDL-C +8.3% vs +2.2% in patients with C-reactive protein ≥ 10 mg/l normalizing upon treatment vs CRP < 10 mg/l throughout treatment period). CONCLUSION: Anti-TNF therapy results in lipid changes mostly when inflammation is appreciably modified.

Autoimmunogenicity during anti-TNF therapy in patients with psoriasis and psoriatic arthritis.

INTRODUCTION: The tumor necrosis factor (TNF-α) was initially described as lymphotoxin or cachectin. The discovery of therapies blocking the action of TNF-α, in 1988, started a new era in the therapy. One of often reported adverse effects related to the use of TNF-α antagonists is induction of the formation of autologous antibodies and antibodies neutralizing anti-TNF drugs. The development of anti-TNF-induced lupus or classical drug-induced lupus is more rarely reported. AIM: To evaluate the presence and the level of anti-nuclear antibodies in patients with psoriasis and psoriatic arthritis and the influence of anti-TNF therapy used on the concentration of antinuclear antibody (ANA). MATERIAL AND METHODS: A total of 28 subjects were included in the study. 71.4% of subjects were diagnosed with psoriatic arthritis and 28.6% with plaque psoriasis. RESULTS: Among the patients with plaque psoriasis, the antinuclear antibodies were found in 25% of subjects and in 80% of patients with psoriatic arthritis. After the treatment an increase in the titer or appearance of antibodies was found in 66.7% in the infliximab group, 18.2% in the etanercept group and 54.7% in the adalimumab group. No subjects developed symptoms of drug-induced systemic lupus. CONCLUSIONS: Our findings have shown that all anti-TNF therapies induced ANA in psoriatic arthritis and psoriatic patients. Considering a mild course of lupus induced by anti-TNF treatment and, usually intrinsic, resolution of symptoms, the biological therapy still appears as a safe treatment for patients.

Is Etanercept 25 mg Once Weekly as Effective as 50 mg at Maintaining Response in Patients with Ankylosing Spondylitis? A Randomized Control Trial.

OBJECTIVE: To investigate, in a pilot randomized controlled trial, whether etanercept (ETN) 25 mg once weekly is effective at maintaining a clinical response in patients with ankylosing spondylitis (AS) who have responded to the standard 50 mg dose. METHODS: Adults with AS not responding to conventional therapies were prescribed ETN 50 mg once weekly for 6 months. Responders as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were randomly assigned to taper to 25 mg once weekly or continue on 50 mg and followed for a further 6 months. The primary outcome measure was maintenance of a 50% reduction in the BASDAI or fall in BASDAI by ≥ 2 units and a ≥ 2-unit reduction in BASDAI spinal pain as measured on a 10-point visual analog scale at 6 months postrandomization. RESULTS: Of 89 patients assessed for eligibility, 59 were enrolled; 47 (80%) had sufficient clinical response and were eligible for randomization, 24 were assigned to continue receiving ETN 50 mg, and 23 to taper to 25 mg. After 6 months, 20 (83%) of the 50 mg arm maintained clinical response compared with 12 (52%) of the 25 mg arm (a difference of -31%, 95% CI -58% - -5%). CONCLUSION: Although this pilot study demonstrates that treatment with ETN 25 mg was less effective at maintaining treatment response in the stepdown phase, 52% of participants maintained treatment response. Future research should address which patients are suitable for tapering.

Performance of the tuberculin skin test and interferon-γ release assays: an update on the accuracy, cutoff stratification, and new potential immune-based approaches.

An association between biologic agents and reactivation of active disease from latent tuberculosis infection (LTBI) has been established. Screening for LTBI is, therefore, now recommended for candidates for biologic drugs. The tuberculin skin test (TST) and interferon-γ release assays (IGRA) are the available commercial tests for detecting LTBI. We discuss their accuracy in immune-competent subjects and patients with autoimmune diseases, as well as potential new approaches to immune diagnosis. IGRA seem to be more accurate than TST in bacillus Calmette-Guerin vaccinated subjects and patients with autoimmune diseases. However, longitudinal studies are needed to estimate the risk of progression to TB after IGRA-based and/or TST-based diagnosis of LTBI in these vulnerable patients. New tests are needed to identify those patients with LTBI who will develop active TB and need prophylaxis.

Anti-TNF therapy in Jordan: a focus on severe infections and tuberculosis.

BACKGROUND: A high rate of infection has been reported in patients receiving treatment with anti-tumor necrosis factor (anti-TNF). This study describes the rate of and risk factors for serious infections in patients receiving anti-TNF agents in Jordan. METHODS: This retrospective observational study was conducted at a large tertiary referral center in the north of Jordan. Between January 2006 and January 2012, 199 patients who received an anti-TNF agent (infliximab, adalimumab, or etanercept) were included. Patients received the anti-TNF treatment for rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, or other conditions. A serious infection was defined as any bacterial, viral, or fungal infection that required hospitalization, administration of appropriate intravenous antimicrobial therapy, and temporary withholding of anti-TNF treatment. RESULTS: The mean duration of anti-TNF treatment was 26.2 months. Steroids were used in 29.1% of patients, while 54.8% were given additional immunosuppressant therapy (methotrexate or azathioprine). Only one anti-TNF agent was given in 70.4% of patients, while 29.6% received different anti-TNF agents for the duration of treatment. Serious infections were documented in 39 patients (19.6%), including respiratory tract infections (41%), urinary tract infections (30.8%), and skin infections (20.5%), and extrapulmonary tuberculosis in three patients (7.7%). Exposure to more than one anti-TNF agent was the only factor associated with a significant increase in the rate of infection (relative risk 1.9, 95% confidence interval 1.06-4.0, P=0.03). CONCLUSION: Serious infections, including tuberculosis, were a common problem in patients receiving anti-TNF agents, and exposure to more than one anti-TNF agent increased the risk of serious infection.

Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs.

OBJECTIVE: The aim of this study was to assess the effects of anti-tumor necrosis factor (TNF) agents or disease-modifying antirheumatic drugs (DMARDs) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients with rheumatic diseases. METHODS: Evidence of HBV reactivation after anti-TNF therapy or DMARDs in HBsAg-positive patients with rheumatic disease was summarized by performing a systematic review. RESULTS: A total of 122 HBsAg-positive rheumatic disease-positive patients undergoing treatment with an anti-TNF agent or with DMARDs were identified in nine studies. In eight of the studies, the anti-TNF agents used were etanercept in 56 cases, adalimumab in 25 cases and infliximab in 14 cases. Follow-up periods ranged from 6 to 52 months. Antiviral prophylaxis was administrated in 48 of the 122 patients (39.3%). HBV reactivation in HBsAg-positive patients taking an anti-TNF agent or DMARD was reported in 15 cases (15/122 = 12.3%). Ten of the 15 patients provided individual data on HBV reactivation: four patients had rheumatoid arthritis, four had ankylosing spondylitis and two had psoriatic arthritis; four received etanercept, and two received infliximab. In one of the four etanercept-treated cases in which the patient had elevated HBV-DNA levels, antiviral prophylaxis was also administered. Antiviral treatment was also administered in seven patients receiving other treatments: lamivudine in one, adefovir in one and entecavir in five. Clinical outcomes were satisfactory in all 10 cases of HBV reactivation. CONCLUSIONS: Hepatitis B virus reactivation was found in 15 (12.3%) patients among the 122 HBsAg-positive patients with rheumatic diseases treated with anti-TNF agents or DMARDs.

Exploring the use of adalimumab for patients with moderate Crohn's disease: subanalyses from induction and maintenance trials.

BACKGROUND: Anti-TNF agents are often reserved for patients with severe Crohn's disease (CD). AIMS: We explored the predictive value of baseline disease activity and C-reactive protein (CRP) for disease course, adalimumab efficacy for remission (induction and maintenance) in patients with moderate and severe CD, and adalimumab efficacy in moderate CD by CRP category. METHODS: Post hoc analyses of remission data were performed for all randomized patients from induction (CLASSIC I) and maintenance (CHARM, EXTEND) adalimumab trials in patients with moderate (CDAI≤300) or severe (CDAI>300) CD, and in high (≥10 mg/L) or low (<10 mg/L) CRP moderate CD subgroups. Placebo-treated CHARM patients were evaluated for disease activity over time and time to CD-related hospitalization, by baseline disease severity and CRP. RESULTS: Moderate CD patients had the highest clinical remission rate and largest treatment effect size compared with placebo at week 4 after 160/80 mg induction (46.3% adalimumab, 17.4% placebo; versus 22.9%, 3.6% for severe patients). Moderate-CD/high-CRP patients had the most pronounced efficacy (57.1% adalimumab, 6.7% placebo; versus 40.7%, 20.0% for lower CRP group). Adalimumab maintenance treatment (40 mg every-other-week) achieved superior remission versus placebo at one year in moderate (32.9% versus 13.7%) and severe (27.2% versus 7.5%) cohorts. Among moderate patients, efficacy was similar by CRP category. Moderate-CD/high-CRP placebo-treated patients experienced disease activity and hospitalization rates at week 56 of CHARM approaching those of severe CD patients. CONCLUSIONS: This analysis suggests that moderate CD patients can be treated effectively with adalimumab, and supports using CRP to identify moderate CD patients at greatest risk of disease progression.

Micobacterioses relacionadas às terapias com imunobiológicos (anti-TNF-a) / Mycobacteriosis related to the immunobiological therapy (anti-TNF-a)

Os antagonistas do fator de necrose tumoral alpha (TNF-a) representam importante avanço na terapia de doenças imunomediadas, tendo mostrado marcante eficácia no tratamento destas, principalmente artrite reumatoide, psoríase, artrite psoriásica, espondilite anquilosante e doença de Crohn. O tratamento é comprovadamente eficaz, porém apresenta risco elevado para o desenvolvimento de micobacterioses, a exemplo da tuberculose e da hanseníase...

Pyloric stenosis associated Crohn's disease responding to adalimumab therapy.

Gastroduodenal Crohn's disease (CD) is rare and the response to standard medical therapy is often poor. Anti-tumor necrosis factor therapy has revolutionised the treatment of CD. We present a patient with pyloric stenosis associated with CD which improved with Adalimumab therapy. We recommend considering anti-tumor necrosis factor therapy in symptomatic gastroduodenal CD.