anti-TNFalpha Therapy Research Articles

2921 Correlation Between the Cumulative Risk of Surgery and Timing of Anti-TNF Initiation in Crohn's Disease

INTRODUCTION: Despite their effectiveness in the management of Crohn's disease (CD), anti-tumor necrosis factor medications' use is often delayed until patients fail conventional therapy. There is more evidence in the literature that the early use of anti-TNF in the disease course may improve the long-term outcomes and decrease the risk of complications. However, the optimal time to start these agents is not well defined. In our study, using patient data at the University of Kansas Medical Center, we aimed to determine the cumulative risk of surgery based on the use of anti-TNF agents during the disease course. METHODS: A retrospective cohort study was conducted evaluating CD patients on anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) seen at the University of Kansas Medical Center until May 2018. The primary outcome was the cumulative risk of surgery based on anti-TNF initiating time. RESULTS: A total of 229 patients with CD were enrolled, 143 in the early anti-TNF alpha group and 86 in the late group. Total of 128/229 required surgery. Our analysis demonstrated a positive correlation between the cumulative incidence of surgery and the duration between diagnosis and initiating anti-TNF alpha therapy. In fact, initiating anti TNF at the time of diagnosis prevented the need for surgery for 80-100% of patients. Whereas initiating anti TNF within 10 years of diagnosis prevented the need for surgery in 50% of the patients and more than 80% of patients who started anti-TNF alpha therapy after 20 years of diagnosis had a need for surgery. CONCLUSION: Our study suggests an increased risk of surgery in Crohn's disease patients with the late use of anti-TNF. Early initiation of anti-TNF alpha therapy at the time of diagnosis was associated with the least risk of the need for surgery.

Clinical manifestations and anti-TNF alpha therapy of juvenile Beh\xe7et\u2019s disease in Taiwan

BackgroundsBehçet’s disease (BD) is a rare vasculitic disorder affecting all sizes of vessels. Among BD patients, 4 to 25% of patients with diagnosed age younger than 16 years old are defined as juvenile BD (JBD). This study aimed to evaluate the clinical manifestations and treatments of patients with JBD, with a particular focus on the effectiveness and safety of anti-tumor necrosis factor (TNF)-alpha therapy.MethodsWe retrospectively reviewed data of all patients diagnosed with JBD at age of 16 years or younger in a tertiary hospital in Taiwan. The clinical manifestations, laboratory data, treatments, disease courses, and clinical outcomes were evaluated. The effectiveness of anti-TNF-alpha therapy was measured based on changes in Behçet’s Disease Current Activity Form (BDCAF) scores, prednisolone dosages and the immunosuppression load scores.ResultsFifty-five patients were included in the study. The median age at disease onset was 11 years. The most common clinical presentation was recurrent oral aphthous ulcers (100%), followed by genital ulceration (69.1%), skin lesions (36.4%), gastrointestinal symptoms (29.1%), ocular involvement (27.3%), and arthralgia (27.3%). Ninety-one percent of the patients fulfilled the International Criteria for Behçet’s Disease, and 36.4% met the Paediatric Behçet’s Disease criteria. The most frequently used medications were prednisolone (74.5%) and colchicine (54.5%). Six patients with refractory or severe JBD received anti-TNF-alpha therapy. These patients were diagnosed at a younger age compared with those who did not receive anti-TNF-alpha therapy (7.5 vs 13 years; P = 0.012), the BDCAF scores reduced significantly at the 1st month, the 6th month and 1 year after the treatment. They did not use steroids after the first year of treatment, and, after treatment for 6 months, their immunosuppression load scores reduced significantly. Due to the limited case numbers, literature reviews of anti-TNF-alpha therapy for refractory JBD were conducted, which had a total 18 JBD patients receiving anti-TNF-alpha therapy, of which fifteen patients had favorable outcomes after treatment with minimal side effects.ConclusionsAnti-TNF-alpha therapy may be necessary for JBD patients with refractory disease courses. Anti-TNF-alpha therapy was effective and safe in these patients, especially regarding its corticosteroid- and immunosuppressive drug-sparing effects.

A prospective clinical investigation of the effects of anti-TNF alpha therapy on exercise capacity in patients with ankylosing spondylitis

Background/aim The purpose of this study was to investigate possible effects of anti-TNF alpha therapy on cardiorespiratory fitness and physical functional capacity of patients with ankylosing spondylitis (AS). Materials and methods Twenty-eight AS patients meeting the modified New York criteria with active disease state and an equivalent number of healthy individuals as the control were prospectively enrolled. Physical working capacity and aerobic exercise capacity of the participants were determined by using cardiopulmonary exercise tests, performed before and 4 months after initiation of anti-TNF alpha therapy. Results The mean age of the patients was 37 ± 9.1 years, and mean duration of disease was 8.9 ± 7.6 years. Patients with AS exhibited significantly lower aerobic exercise capacity (VO2peak: 21.2 ± 5.5 vs. 27.2 ± 6.6 ml/kg/min, P = 0.001), maximum power output (110.4 ± 34.8 vs. 153 ± 39.8 W, P = 0.0001), and exercise duration (16.3 ± 2.6 vs. 19.6 ± 2.9 min, P = 0.0001) than the healthy controls. When patients were reevaluated after 4 months of anti-TNF alpha therapy, significant improvement was obtained in patients’ aerobic capacity, maximum power output, and exercise duration.Conclusion Results from this study indicate that in addition to inflammatory parameters and quality of life index, even short-term anti-TNF alpha therapy results in significant improvement in cardiopulmonary health status as objectively reflected by peak VO2, maximum work rate, and exercise duration.

Pericardial Effusion Due to Infliximab Therapy for Ulcerative Colitis

Ulcerative colitis (UC) is characterized by ulcers and inflammation of the colon, with anti tumor necrosis factor alpha (anti-TNF alpha) therapy as a mainstay for treatment. Side effects include anti-TNF alpha induced lupus (ATIL), which consists mostly of arthralgias and cutaneous manifestations with rare cases of pleural or pericardial effusions. Serology shows positive anti nuclear antibodies (ANA) (79%), positive anti double stranded DNA (ds-DNA) antibodies (72%) and rarely anti histone antibodies (17-57%). We present a case of infliximab induced pericardial effusion (PE). A 51 year old female with UC on mesalamine, presented to clinic with watery diarrhea and abdominal pain. She was prescribed budesonide and prednisone with no improvement, so infliximab therapy was initiated. 2 weeks after receiving her 1st dose of infliximab 500 mg, she developed shortness of breath, mid sternal chest pain and fatigue. A transthoracic echocardiogram showed a small to moderate PE present more anteriorly and less prominent on the apical, inferior and subcostal views. Criteria for cardiac tamponade was not met. Due to the anatomical location of the effusion, a pericardiocentesis was not done. Workup for the etiology of the PE including HIV, monospot, T-spot, ANA, and anti ds-DNA antibody was negative. Anti histone antibodies were 1.9 (positive). Due to the timeline of her symptoms corresponding with infliximab, a diagnosis of ATIL was made. Infliximab was stopped and in a few days her symptoms resolved. She was later switched to vedolizumab for UC with no adverse effects. No definitive criteria is present to diagnose ATIL. However, early diagnosis of ATIL requires an association between symptoms and the drug, at least one serologic American College of Rheumatology (ACR) criteria (ANA, anti ds-DNA antibodies, anti histone antibodies) and one non serologic ACR criteria (arthritis, serositis, rash). This case is a rare presentation of infliximab induced lupus, presenting as PE with negative ANA and anti ds-DNA antibodies, but positive anti histone antibodies. Ideal treatment is discontinuation of the drug. Steroids may be required in some cases. Alternate therapy for UC like vedolizumab has been shown to be effective and safe. After vedolizumab therapy, our patient had complete resolution of symptoms with no side effects. Further research is warranted to come up with a definitive criteria for diagnosis of ATIL given its life threatening and variable manifestations.2087_A Figure 1. Parasternal long axis view of the pericardial effusion.2087_B Figure 2. Subcostal view of the pericardial effusion.2087_C Figure 3. Timeline of the symptoms.

A multicenter retrospective case-control study on Suspension of TNF-inhibitors and Outcomes in Psoriatic patients (STOP study).

There is limited information on patients undergoing withdrawal after long-term treatment with anti-TNF alpha drugs and their clinical evolution during the post-interruption period in real-life settings. The purpose of the present retrospective case-control study was to provide a clearer insight into the clinical management of psoriatic patients with adequate response to long-term adalimumab, etanercept and infliximab treatment once these biologic agents are interrupted. A total of 270 patients undergoing anti-TNF alpha agents discontinuation and 253 controls treated with a continuous regimen were enrolled. The primary endpoint was the change in disease activity in each study group over six months (or until treatment of psoriatic recurrence) as measured by the PASI score every month. Then, we evaluated the rate of and time to relapse, the rate of clinical worsening (PASI≥5) and the clinical variables influencing the loss of response. Our study showed that about 50% of patients achieving a long-term and optimal response to the aforementioned anti-TNF alpha agents did not experience any relapse over a 6-month follow-up period after withdrawal. We also observed that subjects displaying a complete remission (PASI=0) at anti-TNF alpha therapy withdrawal experienced less frequently disease worsening and/or relapse compared to subjects having a PASI>0. Our findings confirmed that all three anti-TNF alpha agents tend to retain their effectiveness upon re-administration in case of recurrence, even if they have been previously used for long time.

Tuberculosis in the era of anti-TNF-alpha therapy: Why does the risk still exist?

Rheumatoid arthritis is an autoimmune systemic disease characterized mainly by inflammatory compromise of diarthrodial joints. Multiple drug therapies have been developed to control the activity of rheumatoid arthritis, among them, the first line of disease-modifying antirheumatic drugs (DMARD), and novel drug therapies such as the anti-TNF alpha therapy, with satisfactory clinical outcomes.Despite this positive fact, the use of this therapy implies the risk of producing negative effects due to its mechanism of action, which has been associated with multiple infections, especially tuberculosis, making it necessary to use screen tests before resorting to this kind of drugs.We present the case of a 58-year-old female patient, with a six-year history of rheumatoid arthritis.The patient developed disseminated tuberculosis with compatible radiological and histological findings after receiving treatment with infliximab (anti-TNF therapy). No test was performed to screen for latent tuberculosis infection prior to the administration of infliximab.The performance of routine screenings tests for tuberculosis prior to anti-TNF alpha therapy plays an essential role in the detection of asymptomatic patients with latent tuberculosis. This is the only way to identify those patients who would benefit from anti-tuberculosis drugs before the initiation of anti-TNF alpha therapy, which makes the difference in the search of a significant reduction in the incidence of tuberculosis and its associated morbidity and mortality.

Postoperative Morbidity Risks Following Ileocolic Resection for Crohn's Disease Treated With Anti-TNF Alpha Therapy: A Retrospective Study of 360 Patients.

Despite the effectiveness of anti-TNF alpha (ATA) treatment to induce and maintain remission in Crohn's disease, surgical intervention is frequently required. Results of previous studies on the impact of anti-TNF on postoperative course are discordant. The aim of this study was to evaluate the impact of ATA on postoperative morbidity following ileocolic resection for Crohn's disease. A retrospective review of Crohn's disease patients undergoing ileocolic resection was performed. Patients receiving medical treatment ≤8 weeks prior to surgery were included and followed up for postoperative morbidity. The Clavien-Dindo classification was used for grading complications. Risk factors for postoperative morbidity were assessed on multivariable analysis. A total of 360 patients underwent ileocolic resection for Crohn's disease between 2002 and 2013; 15.3% of patients had ATA ≤8 weeks prior to surgery. Laparoscopic resections were performed in 110 cases (31%), of which 6% were converted to an open operation. Primary anastomosis without the formation of a diverting ileostomy was performed in 301 cases. Overall morbidity was 24.2%, with a mortality rate of 0.8%. ATA use prior to surgery was identified as an independent risk factor for overall morbidity (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.08-3.82; P = 0.027) and septic complications (OR, 2.14; 95% CI, 1.03-4.29; P = 0.04). In subgroup analysis of patients with a primary anastomosis, ATA use had no significant impact on septic or overall morbidity. Preoperative ATA use is a risk factor for overall postoperative morbidity and septic complications. However, the formation of a primary anastomosis should not be influenced by preoperative ATA use.

Relationship between etanercept and thyroid function in patients with psoriasis vulgaris.

Background and aimPsoriasis vulgaris, a chronic inflammatory skin disease, requires a long term medication, in order to avoid relapsing episodes. TNF-alpha, one of the targeted molecule in psoriasis therapy, seems to be also involved in thyroid disorders etiopathogenesis. The aim of this study was to evaluate the relationship between anti TNF-alpha therapy and thyroid parameters: serum level of triiodothyronine (T3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and antithyroidperoxidase antibody (AbTPO) in psoriasis treated population.MethodsThe study was performed on 44 patients with psoriasis vulgaris (20 patients under antiTNF-alpha treatment (etanercept), 24 patients with no previous systemic therapy). Serum concentrations of hormones, AbAntiTPO and TNF-alpha were measured and a thyroid ultrasonographic evaluation was performed for each patient.ResultsThe mean serum level of FT4 was significantly higher in patients with no systemic treatment (p<0.05). The patients treated with etanercept had a significantly higher level of TNF-alpha (p<0.05). No significant difference was observed for the other evaluated parameters. Also, we found a significant negative correlation between TNF-alpha and TSH levels (r=−0.366, p=0.015).ConclusionsWe only found that the mean level of FT4 was significantly higher in patients with no systemic treatment. Also, a negative strong correlation was seen between serum level of TSH and TNF-alpha. Based on our data, comparison with other anti TNF-alpha therapies might be of interest in future studies.

Case Series of Crohnʼs Disease Patients Refractory to Anti-TNF Alpha Therapy on Uztekinumab

Introduction: Uztekinumab blocks interleukins 12 and 23 through their common p40 subunit and has been previously used in the U.S. for the treatment of plaque psoriasis and psoriatic arthritis. It just recently got FDA approval for treatment of patients with moderate to severe Crohn's disease refractory to one or more Anti TNF-α after promising results from three pivotal phase 3 clinical trials with over 1300 patients. Our study aims to assess the effectiveness and safety of uztekinumab in refractory patients with Crohn's in real-life practice on our population. Methods: A retrospective chart review was performed with inclusion criteria of patients with Crohn's disease refractory to Anti TNF-α therapy and currently on uztekinumab. Demographic factors including age, sex, onset of disease with duration were gathered. Treatments previously received and number of surgeries were used to gauge disease severity. Remission was defined as lack of diarrhea, rectal bleeding, abdominal pain, nausea, vomiting. Data for side-effects of uztekinumab was also gathered. Results: There were a total of 5 patients: 2 were females and 3 were males. The age of onset ranged from 13-34 years with disease duration ranging from 15-25 years. All patients received a minimum of 3 months of therapy with one patient on uztekinumab for over 2 years. Induction therapy that was weight based starting 0, 4 and 16 weeks followed by maintenance of every 12 weeks was used on all patients. All of these patients could be classified as severe given all of them received at least one major surgery including proctocolectomy, Ileal resection, diverting ileostomy, ileocolectomy and had failed multiple medications (as mentioned on table 1). All our patients achieved clinical remission with 3 completely off steroids and 2 being tapered of steroids. Three patients had peri-anal disease with improvement after the start of therapy. Uztekinumab was tolerated well with no side-effects noted including opportunistic infections, allergic reactions, neurologic and cardiovascular side-effects. Conclusion: Uztekinumab which is just recently FDA approved is showing promising results in our series of patients. It should be strongly considered on patients refractory of Anti TNF-α therapy as it is able to achieve IBD quality measures with steroid sparing therapy and improved bone health which ultimately improves overall patient outcomes and quality of life.Table: Table. Patient characteristic and their outcomes

The Effect of Anti TNF-Alpha Therapy in Nutritional Status and Serum Leptin Levels in Patients with Ankylosing Spondylitis

The objective of this study was to investigate the effect of anti TNF-α therapy on nutritional status and serum leptin levels in patients with ankylosing spondylitis.<b> </b>This study was conducted on two groups of AS patients. First group included 48 patients receiving anti TNF-α treatment together with NSAID. Second group included 48 patients receiving only NSAID treatment. Descriptive information, food consumption and physical activity about patients collected with a survey. Anthropometric measurements were measured with body analysis scale and serum leptin was also assessed. As results, there was significant difference in daily energy consumption between both men and women with and without anti TNF-α treatment (2399 kcal and 2069 kcal p=0,036, 2102 kcal and 1659 kcal p=0,001). There was no significant difference of serum leptin levels between patients receiving anti TNF-α and only NSAID treatment (p>0,05). However, the women's leptin levels (12,4±8,2 ng/mL) were significantly higher compared to men (3,7±3,02 ng/mL). There was positive correlation of serum leptin levels, BMI and body fat mass between men and women with and without anti TNF-α treatment. The anthropometric measurements between both men and women groups were not significant (p>0,05). No statistical difference was found between the physical activity assessments of the groups (p>0,05).<b> </b>In conclusion,<b> </b>there was no significant effect of anti-TNF-α treatment in AS patients on serum leptin levels, physical activity, and anthropometric measurements. However, anti TNF-α therapy receiving patients’ daily energy and nutrient consumption were higher. This study showed anti TNF-α therapy has been effective on food consumption of patients with ankylosing spondylitis.

Functional Toll-Like Receptor (TLR)2 polymorphisms in the susceptibility to inflammatory bowel disease.

BackgroundThe recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) suggest significant genetic overlap with complex mycobacterial diseases like tuberculosis or leprosy. TLR variants have previously been linked to susceptibility for mycobacterial diseases. Here we investigated the contribution to IBD risk of two TLR2 polymorphisms, the low-prevalence variant Arg753Gln and the GTn microsatellite repeat polymorphism in intron 2. We studied association with disease, possible correlations with phenotype and gene-gene interactions.Methodology/Principal findingsWe conducted a large study in 843 patients with Crohn’s disease, 426 patients with ulcerative colitis and 805 healthy, unrelated controls, all of European origin. Overall, the frequency for carriers of shorter GTn repeats in intron 2 of the TLR2 gene, which have previously been associated with low TLR2 expression and high IL-10 production, was slightly elevated in Crohn’s disease and ulcerative colitis compared to healthy controls (16.0% resp. 16.7% vs. 12.8%). The highest frequency of short GTn carriers was noted among IBD patients on anti TNF-alpha therapy. However, none of these differences was significant in the multivariate analysis. The Arg753Gln polymorphism showed no association with any clinical subtype of IBD, including extensive colitis, for which such an association was previously described. We found no association with specific phenotypic disease subgroups. Also, epistasis analysis revealed no significant interactions between the two TLR2 variants and confirmed IBD susceptibility genes.ConclusionsThe two functional relevant polymorphisms in TLR2, the GTn microsatellite repeat polymorphism in intron 2 and the Arg753Gln variant do not seem to play a role in the susceptibility to Crohn’s disease or ulcerative colitis.

Different effects of anti-TNF-alpha biologic drugs on the small bowel macroscopic inflammation in patients with ankylosing spondylitis

Considering the ability of anti-TNF alpha drugs to lower the burden intestinal inflammation in patients with inflammatory bowel disease (IBD), and the similarity between IBD and ankylosing spondylitis (AS) regarding inflammatory intestinal involvement, we aimed to investigate the impact of anti-TNF alpha biologic therapy on subclinical intestinal inflammation in AS patients. Between January 2008 and December 2013, 38 AS patients and 23 controls were enrolled in the study and investigated with small bowel videocapsule endoscopy examination and ileocolonoscopy. Each tertile of the small bowel (proximal, mid and distal) was assessed by calculating the Lewis score based on the image stream. The Lewis scores were significantly higher in the AS group compared to controls (580.9 ± 818 vs. 81 ± 121, p<0.001). 16 patients (42.1%) were on anti-TNF alpha therapy (Adalimumab (n = 5), Infliximab (n = 5) or Etanercept (n = 6)).31.3% of them used NSAIDs simultaneously, compared with 77.3% of the other patients (p<0.01). Their Lewis scores were lower compared to the other patients for the entire small bowel (306 ± 164 vs. 790 ± 1038, p = 0.015), its proximal and distal tertiles (238 ± 154 vs. 560 ± 543, p = 0.021, and 140 ± 189 vs. 300 ± 220, p = 0.027, respectively). The Lewis score was also lower in patients receiving Adalimumab/Infliximab compared to those on Etanercept for the entire bowel and its distal tertile (262 ± 165 vs. 380 ± 148, p = 0.069 and 62 ± 101 vs. 273 ± 236, p = 0.060, respectively). Anti-TNF alpha therapy in patients with AS reduces the subclinical intestinal inflammation, but the magnitude seems to depend upon the class anti-TNF alpha agent used (Clinical Trials. gov NCT00768950).

Inflammatory bowel disease as a paradoxical effect of anti-TNF alpha therapy

Anti-TNF-α therapies are used in the treatment of different inflammatory conditions, such as inflammatory bowel disease (IBD). However, paradoxical effects may occur during treatment. In other words, these drugs can induce or unmask diseases similar to those they were intended to treat. Etanercept is the main anti-TNF-α agent associated with the development of paradoxical IBD; this drug, moreover, has no proven usefulness in the treatment of the disease. This association, which is not coincidental and meets the criteria for a temporal causal association, is infrequent and is seen particularly in patients with spondyloarthritis. Restarting treatment with etanercept may induce new intestinal symptoms. There are no endoscopic, histopathologic or clinical differences between primary and secondary IBD, and both are diagnosed in the same way. The most frequent presentation is Crohn disease. When a paradoxical event occurs, etanercept is usually replaced with infliximab, which has not been associated with disease recurrence.

Efficacy of Anti-TNF-α Therapy for the Treatment of Non-infectious Uveitis: A Retrospective Study of 21 Patients

ABSTRACTPurpose: To assess the efficacy of anti-TNF alpha (TNF-α) therapy in patients with non-infectious uveitis.Methods: This was a monocentric observational study of 21 patients with non-infectious uveitis treated with anti-TNF-alpha. The primary endpoint was the control of ocular inflammation. The secondary endpoints included the study of macular thickness and visual acuity, changes in other treatments, and adverse effects.Results: The etiologies of uveitis were Behçet disease (33.3%), birdshot (14.3%), sarcoidosis (9.5%), and idiopathic uveitis (42.9%). Ocular inflammation was controlled at 3 months for 80.9% of patients, at 6 months for 94.7%, at 12 months for 83.3%, and at >12 months for 86.7%. Central macular thickness improved from 452 µm at baseline to 307.5 µm at 12 months (p = 0.002). Visual acuity also improved from 0.51(logMAR) before treatment to 0.24 at 12 months. The mean daily dose of prednisone decreased from 19.7 mg before treatment to 5.2 mg at 12 months (p < 0.001). A total of 9.5% of patients experienced serious side-effects.Conclusions: Our study confirms the efficacy of anti-TNF for the control of short-term and long-term ocular inflammation, with high rates of complete clinical remission.

Magnetic resonance enterography changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn's disease: correlation with SES-CD and clinical-biological markers.

BackgroundIn recent years, the use of MRI in patients with Crohn’s disease (CD) has increased. However, few data are available on how MRI parameters of active disease change during treatment with anti-TNF and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. The aim of this study was to determine the changes over time in MRI parameters during treatment with anti-TNF in patients with CD, and to verify the correlation between MRI score, endoscopic appearance and clinical-biological markers.MethodsWe performed a prospective single centre study of 27 patients with active CD (18 males and 9 females; median age of 27,4 ys; age range, 19–49). All patients underwent ileocolonoscopy and MRI at baseline and 26 weeks after anti-TNF therapy. Endoscopic severity was graded according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) was calculated. Patients underwent clinical evaluation (CDAI) and the C-reactive protein (CRP) level was measured. The associations between variables were assessed with Pearson’s bivariate correlation analysis.ResultsA total of 135 intestinal segments were studied. The median patient age was 27,4 years, 67 % were male and the mean disease duration was 6,1 years. For induction of remission, 18 patients were treated with infliximab and 9 with adalimumab. The mean SES-CD and MaRIA scores significantly changed at week 26 (SES-CD: 14,7 ± 8,9 at baseline vs. 4,4 ± 4,6 at 26 weeks - p < 0.001; MaRIA: 41,1 ± 14,8 at baseline vs. 32,8 ± 11,7 at 26 weeks - p < 0.001). Also the CDAI and serum levels of CRP decreased significantly following treatment (p < 0.001). The overall MaRIA correlated with endoscopic score and with clinical activity (CDAI) both at baseline and at week 26 (p < 0.05). The correlation between overall MaRIA and CRP was significant only at week 26 (p < 0.001).ConclusionsThe MaRIA has a good correlation with SES-CD, a high accuracy for prediction of endoscopic mucosal healing and is a reliable indicator to monitor the use of TNF antagonists in patients with CD.

Tu1917 Risk of Pregnancy Related Complications With Anti-TNFalpha Therapy in Immune Mediated Diseases; A Systematic Review and Meta-Analysis

Tu1917 Risk of Pregnancy Related Complications With Anti-TNFalpha Therapy in Immune Mediated Diseases; A Systematic Review and Meta-Analysis

The Effect of anti-TNFα Induction Therapy on the Nutritional Status and Dietary Intake in Inflammatory Bowel Disease.

Patients suffering from inflammatory bowel disease (IBD) are at a high risk of malnutrition and retain an altered body composition. We hypothesized that anti-tumor necrosis factor (anti-TNF) alpha therapy may improve dietary intake and have a beneficial influence on body composition in these patients. Our study involved 40 IBD outpatients (33 Crohn's disease, 7 ulcerative colitis); 24 of these received adalimumab (160/80/40EOW) and 16 were treated with infliximab (5 mg/kg at week 0, 2, 6, and subsequently every 8 weeks). Body composition was measured with bioelectrical impedance analysis, while dietary intake was recorded prior to initiating biologicals and 3 months afterwards. Body composition indexes: fat-free mass index [FFMI], body fat mass index [BFMI]) were calculated in kg/m2. Baseline BMI (kg/m2) and muscle parameters increased significantly at the end of the observational period (BMI: 23.81+/-7.19 vs. 24.52+/-7.34, p<0.001; FFMI: 17.64+/-3.00 vs. 18.14+/-3.08, p<0.001; at week 0 vs. 12, respectively). However, no significant changes were detected in the fat parameters (BFMI: 6.21+/-5.20 vs. 6.44+/-5.27, respectively). We found no significant difference between the effects of adalimumab vs. infliximab on body composition (deltaFFMI: 0.55+/-0.82 vs. 0.43+/-0.69; deltaBFMI: 0.23+/-0.85 vs. 0.21+/-1.01, respectively). No significant difference was observed in the extent of changes in parameters whether the patients were on corticosteroids (n=15) or not (n=25) at week 0 (deltaFFMI: 0.44+/-0.84 vs 0.59+/-0.72; deltaBFMI: 0.36+/-1.12 vs. 0.09+/-0.71, respectively). Our findings suggest that muscle parameters improved during the anti-TNF induction therapy, while fat parameters did not change significantly. Thus, induction anti-TNF therapy might have a beneficial effect on body composition.

P337. Anti-TNFalpha therapy is associated with rapid reduction of circulating monocyte numbers and blunted monocyte pro-inflammatory response in patients with Crohn’s disease

P337. Anti-TNFalpha therapy is associated with rapid reduction of circulating monocyte numbers and blunted monocyte pro-inflammatory response in patients with Crohn’s disease

Ulcerative Colitis: Update on Medical Management

Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose pathogenesis is multifactorial and includes influences from genes, the environment, and the gut microbiome. Recent advances in diagnosis and treatment have led to significant improvement in managing the disease. Disease monitoring with the use of therapeutic drug monitoring, stool markers, and assessment of mucosal healing have garnered much attention. The recent approval of vedolizumab for treatment of moderate to severe UC has been a welcome addition. Newer biologics, including those targeting the Janus tyrosine kinase (JAK) pathway, are on the horizon to add to the current armamentarium of anti-TNF alpha and anti-integrin therapies. The recent publication of the SCENIC consensus statement on surveillance and management of dysplasia in UC patients supports the use of chromoendoscopy over random biopsies in detecting dysplasia. This review highlights these recent advances along with others that have been made with ulcerative colitis.

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study.

Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti-TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment. To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti-TNF alpha and to analyse its clinical correlates. A retrospective cohort study on all IBD patients who started anti-TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time-dependent predictors were updated at each available time point. Four hundred and two patients were included. Participants contributed a total of 839 person-years of follow-up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person-years. Cox-regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36-4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12-0.92; P = 0.03). Paradoxical psoriasis is a relevant side effect of anti-TNF alpha therapy, with an incidence rate of five per 100 person-years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti-TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.