Anti-tumor Necrosis Factor Alpha Therapy Research Articles

Biological Agents in the Treatment of Crohn's Disease: A Propensity Score-Matched Analysis From the Prospective Persistence Australian National IBD Cohort (PANIC3) Study.

Comparative effectiveness research provides data on the relative benefits and risks between treatments. In Crohn's disease (CD), however, there are few head-to-head studies comparing advanced therapies and none with long-term follow-up. Real-world effectiveness, defined by treatment persistence, obtained from prospective population-based patient cohorts, may help determine the best sequencing and positioning of biological agents. We analyzed the prospectively collected population-based Australian national Pharmaceutical Benefits Scheme dispensing data registry (2005-2019) for CD. There is no mandated biological agent prescribing order, and all citizens and permanent residents are eligible for treatment irrespective of insurance status. Propensity score matching was performed to reduce selection bias. There were 2,029 lines of therapy in 1,446 patients (median age 43 years, interquartile range 34-58, 44% male patients) over the 15-year period with 5,618 patient-years of follow-up. Per line of therapy, 915/2,029 (45.1%) patients used adalimumab, 722/2,029 (35.6%) used infliximab, 155/2,029 (7.6%) used vedolizumab, and 237/2,029 (11.7%) used ustekinumab. When used in biological agent-naive patients, there was no difference in persistence between any agent ( P > 0.05). Used after first line in biological agent-experienced CD, ustekinumab had significantly better persistence than non-ustekinumab biological agents ( P = 0.0018), vs anti-tumor necrosis factor (TNF) alpha therapy ( P = 0.006) or vedolizumab ( P < 0.001). Ustekinumab persistence was unaffected by prior biological agent exposure ( P = 0.51). After anti-TNF use, ustekinumab had superior persistence to an alternative anti-TNF agent ( P = 0.033) and to vedolizumab ( P = 0.026). Using a propensity score-matched analysis adjusted for age, immunomodulator use, and bio-exposed status, ustekinumab had superior persistence to anti-TNF ( P = 0.01). Multivariate predictors of worse persistence were the use of a non-ustekinumab biological agent (adjusted hazard ratio 2.10, P < 0.001), and bio-experienced status (adjusted hazard ratio 1.23, P < 0.001). This large national prospective database with nonhierarchical prescribing of biological agents did not identify superior persistence of any agent in bio-naive CD. However, for patients with bio-experienced CD, persistence was greater with ustekinumab.

Tofacitinib therapy for severe pyoderma gangrenosum in a patient with enteropathic arthritis: a case-based review.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that is associated with systemic inflammatory conditions. Currently, there is no universally accepted standard therapy for PG, but immunosuppressive (IS) treatment seems essential. We report a patient here who was successfully treated with tofacitinib despite being PG-refractory to multiple anti-tumor necrosis factor alpha (anti-TNF) therapies and conventional IS. In addition, we performed a comprehensive review of all cases of PG treated with JAK inhibitors. We identified 27 cases treated with JAK inhibitors. Approximately 80% of the patients achieved complete recovery within a median of 12weeks, even though 17 patients (63%) had received biologics before JAKinib treatment. Notably, this recovery could appear as early as 2weeks. JAK inhibitors may prove useful in the future, particularly for treating immunosuppressive and steroid-resistant pyoderma gangrenosum, according to recent case reports.

Evidence-Based Approach to Chronic Antibiotic Refractory Pouchitis: A Review.

Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers. The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis. Studies were identified through a search of the PubMed database from the National Library of Medicine. We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years. Studies examining pharmacologic and select nonpharmacologic interventions were included. Outcomes measures included clinical, endoscopic, and histologic end points. Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain. Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes. Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .

Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: A systematic review and meta-analysis.

This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet's uveitis (BU) using meta-analysis. We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute's case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model. Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment. Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

Prediction of response to anti-TNFα using integrative computational approaches in Crohn’s disease—Needle in a haystack or a promising biomarker?

In the January issue of Cell Reports Medicine, Gerassy-Vainberg etal.1 demonstrate the utility of integrative methods to reveal molecular mechanisms associated with anti-tumor necrosis factor-alpha therapy response in patients with inflammatory conditions.

Compositional and functional alteration of gut microbiota profiles in response to anti-TNF-α therapy in inflammatory bowel disease: A Pilot study

Background and aimInflammatory bowel disease (IBD) is a chronic and relapsing disorder that is strongly linked to intestinal microbiota alteration (dysbiosis). Anti-tumor necrosis factor-alpha (anti-TNF-α) therapies have revolutionized IBD treatment over the last two decades. Clinical response to anti-TNF-α treatment generally involves alteration of the gut microbiota composition, although change in the microbiome following therapy has generated some contradictory theories. We examine the composition and function of the intestinal microbiota following treatment with TNF-α inhibitors and examine this relationship in the context of clinical and endoscopic response in a cohort of IBD patients in Saudi Arabia. MethodAn analysis of fecal-derived microbiota in 20 human samples was performed using 16S rRNA gene-based microbiota profiling and next generation sequencing, utilizing Illumina MiSeq. Ten samples were collected at baseline prior to treatment with TNF-α antagonists and ten samples were collected following treatment. Inter- and intra-species variation was tested using ɑ-diversity and β-diversity metrics along with appropriate statistical analysis. An examination of functional metagenomic profile variation was performed following biologics exposure. ResultsA total of 5 087 721 clean-paired sequence reads were generated across subjects before and after biologics treatment and assigned to 401 different operational taxonomic units (OTUs). The two taxonomic microbial groups (before and after treatment) demonstrated no clear separation. Anti-TNF-α treatments induced more specific variation, rather than involving a global impact on the gastrointestinal (GI) microbiota profiles, with a statistically significant increase in the Firmicutes (P = 0.01) and a statistically significant decrease in Proteobacteria (P = 0.04). This was accompanied by a remarkable increase in protective taxa, responsible for short-chain fatty acids production, such as the Lachnospiraceae family, which belongs to the Clostridiales order (P = 0.005). A notable increase in F. prausnitzii and a decrease in the relative abundance of E. coli were observed. At the functional level, an up-regulation in the carbohydrate metabolism pathway was shown in addition to a down-regulation in cellular process and signaling pathways (P = 0.04, P = 0.006, respectively). ConclusionTNF-α antagonists reduced GI microbiota with pro-inflammatory capacity enabling protective bacteria to thrive. The biologics caused specific compositional and functional variation rather than a global alteration of the gut microbiota profile in biologic-responsive IBD patients, leading to an improvement in treatment efficacy.

Biologic Therapy in Inflammatory Bowel Disease - Results from a Single Tertiary Care Center in North Macedonia.

Medical therapies used for Inflammatory Bowel Disease (IBD) include conventional (e.g. 5-aminosalicylates, steroids, immunomodulators) and biologic (e.g. inhibitors of tumor necrosis factor - alpha, integrin inhibitors, interleukin inhibitors) medications. Biologics, due to their high cost, were unfortunately not covered by the public health insurance system in North Macedonia until 2019 and, therefore, not widely utilized for our IBD patients. In 2019, the University Clinic of Gastroenterology and Hepatology in Skopje developed a biologic therapy supply, provided by the National Health Insurance Fund, making this therapy available for a larger number of patients. This report presents the initial results of our prospective, single tertiary-care center study on the effects of biologic therapy in patients with IBD in North Macedonia. The study is focused on the evaluation of clinical outcomes after anti-tumor necrosis factor alpha (anti TNF-alpha) therapy in IBD patients with prior inadequate response to conventional medications.

Comparison of infliximab with adalimumab in biologic-naïve patients with Crohn's disease: a single-center 13-year experience.

Long-term comparison studies between infliximab (IFX) and adalimumab (ADA) with or without immunomodulator therapy are still needed in Crohn's disease (CD). In this study, we evaluated IFX and ADA for long-term clinical effectiveness and safety in CD patients who had not previously received a biologic treatment. The data of adult CD patients were collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related abdominal surgery, steroid use, and serious infections. Out of 224 CD patients, 101 started IFX first (median age: 38.12 years, 61.4% male), while 123 started ADA first (median age: 30.2 years, 64.2% male). The disease durations were 7.01 years and 6.91 years for IFX and ADA, respectively. There were no significant differences between the two groups with respect to age, gender, smoking, immunomodulator usage, and disease activity score at the onset of anti-TNF therapy (p>0.05). Overall, the median follow-up time was 2.36 and 1.86 years after starting anti-tumor necrosis factor-alpha (anti-TNF) therapy in the IFX and ADA groups, respectively. Steroid use (4.0% vs. 10.6%, p=0.109), hospitalization for CD (13.9% vs. 22.8%, p=0.127), abdominal surgery for CD (9.9% vs. 13.0%, p=0.608), and major infections (1.0% vs. 0.8%, p>0.999) did not differ significantly from one another. There were also no significant differences in the rates of these outcomes between concomitant immunomodulator therapy and monotherapy (p>0.05). In this study, we observed no significant differences in the long-term effectiveness and safety of IFX and ADA in biologic-naïve patients with CD.

The effect of etanercept therapy on adrenal steroid metabolism in juvenile idiopathic arthritis: a steroid metabolomics approach

ObjectiveTo evaluate the impact of anti-tumor necrosis factor-alpha (TNFα: etanercept [Etanercept ®]) therapy on adrenal activity in juvenile idiopathic arthritis (JIA) .MethodEleven JIA patients aged 12 ± 6.2 years with a disease duration of 6.3 ± 5.2 years were enrolled. They were treated once weekly with etanercept (0.8 mg/kg) for 3 ± 2.8 years. Urine samples for gas chromatography-mass spectrometry steroid hormone analysis were collected before, and 1 and 3 days after etanercept injection and compared to age- and sex-matched healthy controls.ResultsThe levels of 21 of the 31 metabolites were low before etanercept treatment. Those 21 metabolites included 4 C19 steroids (androgens), 5 C C21 steroid hormone intermediates, 10 cortisol metabolites, and 2 corticosterone metabolites. One day after treatment, only 5 of the 21 metabolite levels remained low. They included 2 C19 metabolites, 2 C21 steroid metabolites and 1 cortisol metabolite β –Cortol (β-Cl). Three days after treatment, the only metabolites levels that continued to be low were 2 C19 metabolite, 2 C21 steroid hormone intermediates and 1 cortisol metabolite α-Cortol (a-Cl), while the remaining 15 metabolites had already normalized after 1 day. Dehydroepiandrosterone-sulfate and 17-hydroxypregnenolone metabolite levels were the last ones to recover. Urinary metabolite ratios reflecting cytochrome P450 CYP21A2 (21-hydroxylase) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzymatic activitieswere lower in JIA patients than in controls, although significant was not reached.ConclusionAlmost all of the pre-etanercept treatment cortisol urinary metabolite levels were significantly lower than normal, and almost all rose to normal values by 1 day after treatment. The therapeutic effect of anti-TNFα treatment in JIA may be related to its effect on the restoration of adrenal function and cortisol levels.

Risk Factors for Surgery in Patients with Intestinal Behçet's Disease During Anti-Tumor Necrosis Factor-Alpha Therapy.

Behçet's disease (BD) is a chronic inflammatory immune-mediated disease involving multiorgan systems. Gastrointestinal (GI) manifestations of BD include abdominal pain, vomiting, GI bleeding, fistula formation, obstruction, and perforation that might require surgery. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) therapy has been shown to have favorable outcomes in patients with intestinal BD who are refractory to conventional therapy. This study sought to figure out the risk factors for undergoing surgery during anti-TNF-α therapy in patients with intestinal BD. In this retrospective analysis of intestinal BD patients who were treated with anti-TNF-α, we collected the baseline patient data including comorbidities, clinical, endoscopic, and radiologic characteristics, and the Disease Activity Index for Intestinal Behçet's Disease at the time of anti-TNF-α initiation. Each potential risk factor was compared. For multivariate analysis, Cox regression was used. A total of 62 patients were considered eligible for analysis, and 15 of them (24.1%) underwent surgery. In univariate analysis, the presence of extraintestinal manifestation, such as joint symptoms and erythrocyte sedimentation rate (ESR), were significantly associated with surgery during therapy. In multivariate analysis, drug response within 4 weeks [hazard ratio (HR), 64.59], skin and joint manifestation (HR, 10.23 and HR, 6.22), geographic ulcer (HR, 743.97), and ESR >42.5 mm/h (HR, 9.16) were found to be factors predictive of undergoing surgery during anti-TNF-α therapy. We found five risk factors predictive of surgery in patients with intestinal BD receiving anti-TNF-α therapy, which can guide physicians in selecting appropriate patients between anti-TNF-α therapy and early surgery.

Growth After Menarche in Pediatric Inflammatory Bowel Disease.

Growth impairment in pediatric patients with pediatric onset inflammatory bowel disease (IBD) is multifactorial. Reports on the effect of age at menarche on adult stature in this population are limited. This study investigated the impact of age at menarche, disease-associated factors, and mid-parental height on growth from menarche to final height (FHt) in pediatric patients with Crohn disease (CD) and ulcerative colitis (UC) and IBD unclassified (IBD-U). Subjects were enrolled from a prospectively maintained pediatric IBD database when IBD preceded menarche and dates of menarche and FHt measurements were recorded. One hundred forty-six patients: CD 112 and UC 30/IBD-U 4. Mean age (years) at diagnosis (10.9 vs 10.1), menarche (14.4 vs 14.0), and FHt (19.6 vs 19.7). CD and UC/IBD-U patients showed significant association between Chronological age (CA) at menarche and FHt (cm, P < 0.001) but not FHt z score (FHt-Z) < -1.0 (P = 0.42). FHt-Z < -2.0 occurred in only 5 patients. Growth impairment (FHt-Z < -1.0) was associated with surgery before menarche (P = 0.03), jejunal disease (P = 0.003), low mid-parental height z score (MPH-Z) (P < 0.001), hospitalization for CD (P = 0.03) but not UC, recurrent corticosteroid, or anti-tumor necrosis factor alpha (anti-TNFα) therapy. Early age of menarche was associated with greater potential for linear growth to FHt but not FHt-Z (P < 0.05). Surgery before menarche, jejunal disease, hospitalization for CD, low MPH, and weight z score were associated with FHt-Z < -1.0.

The Effect of Anti-Tumor Necrosis Factor-Alpha Therapy within 12 Weeks Prior to Surgery on Postoperative Complications in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

The rate of abdominal surgical interventions and associated postoperative complications in inflammatory bowel disease (IBD) patients is still substantially high. There is an ongoing debate as to whether or not patients who undergo treatment with anti-tumor necrosis factor-alpha (TNF-α) agents may have an increased risk for general and surgical postoperative complications. Therefore, a systematic review and meta-analysis was conducted in order to assess the effect of anti-TNF-α treatment within 12 weeks (washout period) prior to abdominal surgery on 30-day postoperative complications in patients with IBD. The results of previously published meta-analyses examining the effect of preoperative anti-TNF-α treatment on postoperative complications reported conflicting findings which is why we specifically focus on the effect of anti-TNF-α treatment within 12 weeks prior to surgery. PubMed, Cochrane, Scopus, Web of Science, World Health Organization Trial Registry, ClinicalTrials.gov and reference lists were searched (June 1995−February 2022) to identify studies, investigating effects of anti-TNF-α treatment prior to abdominal surgery on postoperative complications in IBD patients. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated and subgroup analyses were performed. In this case, 55 cohort studies (22,714 patients) were included. Overall, postoperative complications (OR, 1.23; 95% CI, 1.04−1.45; p = 0.02), readmission (OR, 1.39; 95% CI, 1.11−1.73; p = 0.004), and intra-abdominal septic complications (OR, 1.89; 95% CI, 1.44−2.49; p < 0.00001) were significantly higher for anti-TNF-α-treated patients. Significantly higher intra-abdominal abscesses and readmission were found for anti-TNF-α-treated CD patients (p = 0.05; p = 0.002). Concomitant treatment with immunosuppressives in <50% of anti-TNF-α-treated patients was associated with significantly lower mortality rates (OR, 0.32; 95% CI, 0.12−0.83; p = 0.02). Anti-TNF-α treatment within 12 weeks prior to surgery is associated with higher short-term postoperative complication rates (general and surgical) for patients with IBD, especially CD.

The assessment of the cardiovascular risk in rheumatoid arthritis patients on anti TNF therapy

Auto-immune rheumatic diseases are characterised by high levels of inflammation that accelerate the development of atherosclerosis, increasing the cardiovascular risk. Direct evaluation of arteries such as of intima media thickness measurement is a simple test that asesses the cerebral and cardiovascular risk. In the initial stages, an increase of the intimal media thickness can be observed. Later on, atherosclerosis (plaques), stenosis and occlusion of the arteries can be identified. Indirect evaluation of the cardiovascular risk can be performed using serological markers - fibrinogen, C reactive protein, estimated sedimentation rate, total cholesterol, low density lipoproteins and high density lipoproteins, homocysteine levels etc. The presence of certain lifestyle factors that increase the risk, such as smoking, sedentarism and associated pathologies such as obesity, diabetes, hypertension were assesed in patients with rheumatoid arthritis. The aim of the study is to prove the relationship between anti-tumor necrosis factor alpha therapy effect on the cardiovascular risk in rheumatoid arthritis patients

Efficacy of Calcineurin Inhibitors for Induction of Remission in Intestinal Behçet's Disease.

The efficacy of calcineurin inhibitors (CNIs) for induction of remission in intestinal Behçet's disease (intestinal BD) has not been explored. A multicenter retrospective case series study of patients with active intestinal BD treated with CNIs (cyclosporin and tacrolimus) was conducted. Of 16 patients, 12 (75%) showed a clinical response and 5 (31.3%) achieved clinical remission after 2 weeks of CNI treatment. Similar efficacy of CNIs was observed even in 7 patients refractory to antitumor necrosis factor-alpha therapies. Endoscopic improvement was observed in 11 of 12 patients. CNIs may be promising treatment options for refractory intestinal BD.

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance.

IntroductionTumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that facilitates malignant cells in immune evasion, survival, and treatment resistance by generating a favorable milieu for them. It is shown to be ectopically produced by malignant/leukemic and immune cells in the tumor microenvironment, providing a tumor-supportive environment and playing an important part in the establishment and progression of malignant cells. It is linked to hyperleukocytosis, high blast count, and poor clinical outcomes in acute leukemia (AL). Considering the varied role and different expression patterns of tumor necrosis factor-alpha in acute leukemia and its clinical relevance, the present study was planned to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia and its correlation with disease outcome. The aim of this study was to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia at the time of diagnosis and after induction chemotherapy.Material and methodsThe study included cases classified as acute leukemia based on morphological examination, bone marrow analysis, and flow cytometry. In all patients with acute leukemia (n = 90) and controls (n = 10), the serum tumor necrosis factor-alpha level was measured using a Diaclone Human ELISA kit (Diaclone, Besancon, France) (solid phase sandwich ELISA) at diagnosis and after induction chemotherapy.ResultsTumor necrosis factor-alpha levels were substantially higher in T-acute lymphoblastic leukemia (T-ALL) cases, followed by acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL), at the time of diagnosis, compared to the control. A significant reduction in serum tumor necrosis factor-alpha level was seen in patients with acute leukemia after induction phase chemotherapy (P < 0.05). Tumor necrosis factor-alpha levels were considerably reduced (P < 0.001) in the majority of acute leukemia cases after the induction phase, while high tumor necrosis factor-alpha levels were positively correlated with incomplete remission status in the remaining cases.ConclusionTumor necrosis factor-alpha is involved in the progression of acute leukemia and its relapse. High levels of tumor necrosis factor-alpha are linked to leukocytosis, high blast counts, and worse survival in patients with acute leukemia. Monitoring of tumor necrosis factor-alpha may be helpful in patients with acute leukemia in view of available antitumor necrosis factor-alpha therapy.

Pediatric inflammatory bowel disease: Fecal calprotectin response to Anti-tumor necrosis factor alpha.

Fecal calprotectin (FC) is a marker of mucosal inflammation in inflammatory bowel disease (IBD). We aimed to assess the effect of anti-tumor necrosis factor alpha (TNFα) therapy on FC levels in children with IBD. The medical records of pediatric patients treated with anti-TNFα agents (2015-2020) were reviewed retrospectively. 63 patients had FC levels measured prior to anti TNFα induction with sequential measurements during follow-up. The main outcome measures were time to FC response according to cutoffs of 250, 150, 100 and 50 µgr/gr. Mean age was 13.6 ± 3 years [females 28 (44.4%), Crohn's 55 (87%)]. Outcomes of < 250, < 150, < 100 and < 50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%), respectively. The median time for achieving these cutoffs was 4.8 (1.8-15.6), 7.9 (2.6-16.4), 10.0 (3.5-20.5) and 18.5 (7.0-64.7) months, respectively. Shorter time from diagnosis to treatment was associated with achievement of FC < 50 µgr/gr (p = 0.03). There was no association between age, disease type, anti-TNFα type, inflammatory markers, disease activity indices at baseline and induction anti-TNFα trough concentration and FC response. FC response was achieved by the majority of patients treated with anti-TNFα within a short period of time. FC normalization in responders required almost one year. Fecal calprotectin response was achieved by the majority of pediatric patients within a relatively short period of time after anti-TNFα induction and maintenance therapy. Fecal calprotectin normalization required an average period of approximately one year in responders. The faster response of fecal calprotectin is associated with shorter time from diagnosis to anti-TNFα treatment. Inflammatory bowel disease treating physicians should be aware of the relatively prolonged time to fecal calprotectin normalization and to allow enough time for anti-TNFα therapy to express its full potential prior to significant interventions.

Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia: a randomized, double-blind, placebo-controlled clinical trial.

This study aimed to investigate the efficacy and safety of antitumor necrosis factor-alpha (TNF-α) therapy using adalimumab in patients with chronic schizophrenia. This is a randomized, double-blind, placebo-controlled clinical trial carried out at Roozbeh Hospital (Tehran, Iran) from June 2020 to October 2021. The patients were randomly divided into two parallel adalimumab + risperidone and placebo + risperidone groups. Participants in the intervention group received adalimumab subcutaneous injection (40 mg) by pen-injector at weeks 0 and 4. Using the Positive and Negative Symptoms Scale (PANSS), patients' positive and negative symptoms were assessed at weeks 0, 4, and 8. Forty patients (20 in each group) were included. PANSS total (t = 4.43, df = 38, P < 0.001), negative (t = 2.88, df = 38, P = 0.006), and general psychopathology (t = 4.06, df = 38, P < 0.001) scores demonstrated a significantly greater decline in adalimumab compared with the placebo group from baseline study endpoint. However, improvement of PANSS positive subscale scores showed no significant difference from the baseline study endpoint. There was no significant between-group difference regarding levels of C-reactive protein, interleukin (IL)-1β, TNF-α, IL-6, and IL-8 at baseline and also at the week 8 visit (P > 0.05 for all). The current study found adalimumab adjunctive therapy effective in treating schizophrenia, particularly its negative and general psychopathology symptoms, with no side effects.

Kaposi's sarcoma in an Ankylosing Spondylitis patient treated with Anti-Tumor Necrosis Factor-Alpha (Anti-TNF-α) Therapy

Tumor necrosis factor-alpha (TNF-α) inhibitors are immunosuppressive agents used in a variety of inflammatory diseases, including rheumatoid arthritis (RA), spondyloarthritis, psoriasis, and inflammatory bowel disease (IBD). Kaposi’s sarcoma (KS) is an angioproliferative disease associated with the human herpes virus 8 (HHV-8). We present a 46-year-old male patient with ankylosing spondylitis (AS) treated with TNF-α inhibitor and developed KS during follow-up. The coexistence of anti-TNF-α treatment with KS is a rare condition. This case is presented to address this rare association. Therefore, keeping in mind KS, which is a type of skin tumor, in such HIV-negative patients in whom immunosuppressive agents are initiated, is essential in terms of early diagnosis, treatment, and prevention of complications.

DOP35 Increasing incidence of pouchitis among patients undergoing ileal pouch-anal anastomosis between 1996 and 2018: A population-based Danish cohort study

Abstract Background Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis (UC) in the first 2 years after ileal pouch-anal anastomosis (IPAA) and analyze time trends of the incidence of pouchitis. Methods We used national registries to establish a population-based cohort of all Danish patients undergoing proctocolectomy with IPAA UC between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after IPAA, evaluated by time period of IPAA. The period of IPAA was categorized as follows: 1996–2000 (pre-biologic-1), 2001–2005 (pre-biologic-2), 2006–2010 (early-anti-TNF), 2011–2014 (expanding anti-TNF), 2015–2018 (current biologic). Pouchitis was defined using a previously developed case-finding definition for use in administrative claims data. Kaplan Meier and Cox Proportional Hazard modeling were utilized in the evaluation of time to development of pouchitis. Results We identified 1,664 patients that underwent an IPAA for UC. The cumulative incidence of pouchitis in the 2 years after IPAA increased throughout the study period, from 40% in 1996–2000, (95% CI:35%-46%) to 55% in 2015–2018, (95% CI:48%-63%, Table 1). Patients undergoing surgery between 2015–2018 also demonstrated an increased risk of pouchitis compared to the earliest study period (1996–2000) after adjusting for sex, age, and socioeconomic status (Hazard Ratio [HR] 1.57, 95% CI:1.20–2.05, Table 2, Figure 1). In a separate model adjusting for the same clinical and demographic factors, there was no significant relationship between the preoperative use of anti-tumor necrosis factor alpha therapy use and the risk of pouchitis when evaluated in the entire population (HR 1.14, 95% CI:0.93–1.40) and when evaluated by time period of surgery. Conclusion This first population-based study demonstrated a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis demonstrated in the most recent era (2015–2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.

Risk of consecutive immunogenic failure in switchers of anti-tumor necrosis factor alpha among patients with inflammatory bowel diseases.

Background:Evidence regarding the risk of immunogenicity in patients with inflammatory bowel disease (IBD) who switched anti-tumor necrosis factor alpha (anti-TNFα) therapies to a subsequent anti-TNFα (either infliximab or adalimumab) is conflicting. We aimed to assess the risk of consecutive immunogenicity to anti-TNFα in a large cohort of patients.Methods:This was a multicenter retrospective study. Medical records of adult and pediatric IBD switchers who had pharmacokinetic data for both agents between 2014 and 2020 were retrieved. Data including age, sex, disease type, duration of therapies, and concomitant use of immunomodulators (IMMs) were recorded.Results:Overall, 164 patients were included [52% female; 88% Crohn’s disease; mean age = 24.4 ± 14.6 years; 108 (66%) switched from infliximab to adalimumab and 56 (34%) vice versa]; 120 (73.1%) patients switched due to an immunogenic failure. Among patients switching therapy from infliximab to adalimumab due to an immunogenic failure immunogenicity to infliximab was significantly associated with consecutive immunogenicity to adalimumab (p = 0.026). Forthy four out of 120 patients (36.6%) with an immunogenic failure to the first anti-TNFα started an IMM with the second anti-TNFα. This combination with IMM was not associated with reduction of consecutive immunogenicity (p = 0.31), but it was associated with longer drug retention (p = 0.007). Multivariate analysis demonstrated that older age at second anti-TNFα, adjusted to the chronology of therapy and sex, was associated with increased immunogenicity to the second anti-TNFα.Conclusion:Patients with IBD who switch from infliximab to adalimumab following an immunogenic failure are at increased risk for consecutive immunogenicity to adalimumab. IMM use after a switch prolongs drug retention.