Anti-tumor Necrosis Factor Treatment Research Articles

Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn's disease.

The pathogenesis of Crohn's disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti-tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.

Mycobacterium marinum infection in a patient with Crohn's disease on anti-tumor necrosis factor treatment.

Mycobacterium marinum infection in a patient with Crohn's disease on anti-tumor necrosis factor treatment.

Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

Perianal fistulas may affect 15-50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis guidelines state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (2). Presenting real-world effectiveness data for darvadstrocel in a Spanish population. Observational retrospective cohort study with prospective data gathering. Fourteen institutions. From November 2019-April 2022, all patients (73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; 3) absence of collections >2 cm confirmed by pelvic MRI scan at the time of surgery. Darvadstrocel treatment. Clinical response (closure of ≥50% of external openings), complete clinical closure (100% of external openings) and radiological closure (no fluid collection >2 cm, no edema or inflammation) evaluated 6 months after treatment. Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%) and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure and vice versa. No serious adverse events were reported. Retrospective. Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, UK, and Japan) and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for treatment of fistulas in Crohn's disease. See Video Abstract.

Effect of anti-tumor necrosis factor therapy on the efficacy of aerobic exercise in patients with ankylosing spondylitis

Background: This study aims to evaluate the effects of aerobic exercise on ankylosing spondylitis (AS) patients' clinical outcomes when combined with anti-tumor necrosis factor (TNF) treatments. Methods: Fifty patients diagnosed with AS participate in the study, with 25 on anti-TNF treatment and 25 off anti-TNF treatment. Patients' age, education, body mass index, smoking habits, symptom duration, date of diagnosis, medication use, comorbidities, and surgical history were assessed. Patients receive instructions to walk for 30 minutes, three times per week for twelve weeks and receive evaluation at weeks 0, 6, and 12. Disease activity is evaluated using Visual Analog Scale (VAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while sleep quality is assessed by the Pittsburgh Sleep Quality Index (PSQI). The Ankylosing Spondylitis Life Quality (ASQoL) is used to measure the quality of life and physical activity is measured by the International Physical Activity Questionnaire (IPAQ). Results: During week 6, VAS, BASDAI, PSQI, and IPAQ scores were significantly lower in both groups, one taking anti-TNF and the other anti-TNF-free, in comparison to baseline and week 12 scores. After undergoing six weeks of aerobic exercise treatment, those taking anti-TNF displayed greater improvements in ASQoL scores in contrast to those who were not taking anti-TNF. Conclusion: Aerobic exercise is an effective intervention for enhancing disease activity, quality of life, sleep quality, and physical activity in patients with AS. Additionally, anti-TNF treatment appears to amplify the clinical benefits associated with exercise and facilitate patients' physical activity.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 μg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

CT-based pancreatic radiomics predicts secondary loss of response to infliximab in biologically naïve patients with Crohn’s disease

ObjectivesPredicting secondary loss of response (SLR) to infliximab (IFX) is paramount for tailoring personalized management regimens. Concurrent pancreatic manifestations in patients with Crohn’s disease (CD) may correlate with SLR to anti-tumor necrosis factor treatment. This work aimed to evaluate the potential of pancreatic radiomics to predict SLR to IFX in biologic-naive individuals with CD.MethodsThree models were developed by logistic regression analyses to identify high-risk subgroup prone to SLR. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and integrated discrimination improvement (IDI) were applied for the verification of model performance. A quantitative nomogram was proposed based on the optimal prediction model, and its reliability was substantiated by 10-fold cross-validation.ResultsIn total, 184 CD patients were enrolled in the period January 2016 to February 2022. The clinical model incorporated age of onset, disease duration, disease location, and disease behavior, whereas the radiomics model consisted of five texture features. These clinical parameters and the radiomics score calculated by selected texture features were applied to build the combined model. Compared to other two models, combined model achieved favorable, significantly improved discrimination power (AUCcombined vs clinical 0.851 vs 0.694, p = 0.02; AUCcombined vs radiomics 0.851 vs 0.740, p = 0.04) and superior clinical usefulness, which was further converted into reliable nomogram with an accuracy of 0.860 and AUC of 0.872.ConclusionsThe first proposed pancreatic-related nomogram represents a credible, noninvasive predictive instrument to assist clinicians in accurately identifying SLR and non-SLR in CD patients.Critical relevance statementThis study first built a visual nomogram incorporating pancreatic texture features and clinical factors, which could facilitate clinicians to make personalized treatment decisions and optimize cost-effectiveness ratio for patients with CD.Key points• The first proposed pancreatic-related model predicts secondary loss of response for infliximab in Crohn’s disease.• The model achieved satisfactory predictive accuracy, calibration ability, and clinical value.• The model-based nomogram has the potential to identify long-term failure in advance and tailor personalized management regimens.Graphical

Bartonella Henselae Related Unilateral Anterior Uveitis and Subsequent Multifocal Retinitis in a Case Under Certolizumab Treatment.

A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery. Anti-tumour necrosis factor treatment is fraught with several ocular side effects including myositis, corneal infiltrates, scleritis, uveitis, optic neuritis, retinal vasculitis and ophthalmoplegia.When a new uveitis episode occurs in cases undergoing anti-tumour necrosis factor therapy, its cause poses a diagnostic challenge as it can have either an infectious or a non-infectious nature.Though very rare, ocular bartonellosis may also occur in immunocompromised individuals and a prompt diagnosis and appropriate treatment can lead to an excellent visual recovery.

Clinical and ultrasonographic enthesitis assessment before and after anti-tumor necrosis factor treatment in patients with spondyloarthritis.

This study aimed to clinically and ultrasonographically evaluate enthesitis in patients with spondyloarthritis (SpA) and to determine enthesitis response to anti-tumor necrosis factor (TNF) treatment. Thirty-one SpA patients (22 males, 9 females; mean age: 39.4±10.9 years; range, 22 to 60 years) who started anti-TNF treatment due to their high disease activity were included in the cross-sectional prospective study between May 2017 and January 2018. Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Quality of Life Questionnaire, Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Metrology Index were recorded. Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Score were utilized for clinical enthesitis evaluation. Patients were ultrasonographically evaluated in accordance with the Madrid Sonographic Enthesitis Index (MASEI) by a blinded sonographer. Patients were clinically and ultrasonographically assessed at baseline and in the third month after the treatment. In the initial evaluation, 24 (77.42%) of the patients had clinical enthesitis, and 30 (96.77%) of the patients had ultrasonographic enthesitis. After anti-TNF treatment, MASES, SPARCC, MASEI-structure, MASEI-thickness, MASEI-bursitis, MASEI-Doppler, MASEI-inflammatory, and MASEI-total scores significantly decreased (p<0.05). There was no significant change in MASEI-damage, MASEI-erosion, and MASEI-calcification scores following the therapy (p>0.05). Anti-TNF treatment may improve clinical and ultrasonographic enthesitis, particularly inflammatory changes. Erosions and calcifications may not ameliorate after three months of anti-TNF treatment.

Psöriazis ve Tüberküloz Konulu Yayınların Analizi

Background: Psoriasis is a relatively common inflammatory disease globally with systemic implications and the treatment of psoriasis has advanced rapidly in recent years. However, current treatments, especially anti tumor necrosis factor (TNF) treatments, can lead to tuberculosis. Objectives: This study's objective was to analyze tuberculosis and psoriasis-related literature that was published between 1970 and 2021 by using scientometric techniques. Methods: In this bibliometric analysis study, the Web of Science database was used to find the articles on psoriasis and tuberculosis that were published between 1970 and 2021. The VOSviewer software program was used to generate visualization knowledge maps including co-citation, co-authorship, co-occurrence, and keyword analysis. Results: A total of 127 documents in the field of psoriasis and tuberculosis were indexed in the Web of Science database. The first reports were in 1971, but until 2004 there was no other publications. Since 2010 the number of publications started to increase. The most of the publications were articles (49.606%) and 91.339% of them were published in Science Citation Index Expanded indexed journals. 576 authors contributed to psoriasis and tuberculosis literature from 36 countries. The United States (n=26), Italy (n=21), Spain (n=12) were the first 3 countries in the number of publications. The most of the articles were from Dermatology (n=93, 73%) and Rheumatology (n=11, 9%) research areas. Conclusion: As can be understood from this current study on psoriasis and tuberculosis, it has become more popular, especially with anti-TNF treatments. This study recommends focusing more on tuberculosis, especially in psoriasis and psoriatic arthritis patients receiving anti-TNF therapy.

Intensified anti-TNF treatment downregulates the phenotype in ulcerative colitis: a 13-year prospective follow-up study

BackgroundModerate to severe ulcerative colitis (UC) is generally treated with a step-up algorithm from 5-aminosalicylic acid (5-ASA) to biological agents. There is no general recommendation if or when to de-escalate or discontinue biological therapy. In this study, we performed biological therapy with anti-tumor necrosis factor (TNF) treatment to endoscopic remission followed by discontinuation of therapy. This is a 13- year follow-up study performed for this treatment algorithm.AimThis study aimed to assess whether the treatment algorithm outlined above influences the UC phenotype toward a milder form and identify potential biomarkers for altering the disease phenotype.MethodsPatients with moderate to severe UC were enrolled from 2004 to 2015 and followed up until 2023 to evaluate disease outcomes. Patients were categorized into subgroups based on the highest treatment level required to attain remission: non-biological therapy, biological therapy, or colectomy. Mucosal TNF mRNA expression levels were measured using real-time PCR.ResultsOut of the 116 patients from the original cohort, 71 individuals who had previously undergone anti-TNF treatment to endoscopic remission and subsequently discontinued anti-TNF therapy were included in the present study. Disease outcomes were registered until 2023. By the end of the observation period, 62% of participants were in remission without biological treatment. Among the 71 patients, 39% never experienced a relapse, 23% relapsed but successfully attained remission with untargeted treatment, 18% relapsed and subsequently received a new sequence of biological therapy, and 20% had colectomy. Normalized mucosal TNF mRNA expression was identified as a significant predictor for clinical outcomes.ConclusionMost UC patients transitioned to a milder disease phenotype without requiring biological therapy. Treating to normalize mucosal TNF expression emerges as a potential biomarker, predicting the downregulation of disease severity.

Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn’s Disease: A Multicenter Study

Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P= .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Impact of anti-tumor necrosis factor treatment on lipid profiles in Korean patients with ankylosing spondylitis.

To investigate the effects of anti-tumor necrosis factor (TNF) treatment on lipid profiles and identify risk factors for an increase in total cholesterol (TC) after the anti-TNF treatment in ankylosing spondylitis (AS) patients. This retrospective cohort study analyzed AS patients who received the first-line anti-TNF treatment. Patients with at least nine months of follow-up were included; those who were under 18 years or on any lipid-lowering agent were excluded. A linear mixed model was used to assess the impact of anti-TNF inhibitors on disease activity and lipid profile (TC, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides [TG]). Univariable and multivariable linear regression were used to identify risk factors for an increase in TC after 3 months of anti-TNF treatment. A total of 315 AS patients were enrolled (78.1% male, median age 32.0 [26.0~41.0]). TC, HDL, and TG levels significantly increased particularly within the first 3 months of anti-TNF treatment, while LDL level did not show significant changes. Changes in inflammatory markers and lipid particles (TC, LDL, TG) were correlated over time, but HDL showed no significant correlation. Older age, higher baseline erythrocyte sedimentation rate, and lower baseline LDL level were related to an increase in TC after 3 months of the anti-TNF treatment. In AS patients, anti-TNF treatment has been found to increase lipid particles, potentially due to its anti-inflammatory effects. Future research should explore the underlying mechanism and the clinical implications of dyslipidemia, particularly the occurrence of cardiovascular events, following anti-TNF treatment in AS patients.

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.

Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn's Disease.

Primary and secondary non-response affects approximately 50% of patients with Crohn's disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn's disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn's disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn's disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn's disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn's disease.

Stimulation of the vagus nerve as atherapeutic principle.

Modulation of the parasympathetic tone leads to extensive physiological reactions at several levels, including the decreased production of proinflammatory cytokines. Many studies have demonstrated that chronic inflammatory diseases are associated with reduced parasympathetic and increased sympathetic activities. Moreover, it was demonstrated that a low parasympathetic and a high sympathetic activity in patients with rheumatoid arthritis (RA) predicts apoor therapeutic response to anti-tumor necrosis factor (TNF) treatment compared to RA patients with amore balanced autonomic nervous system. The autonomic equilibrium could be restored by electrical stimulation of the vagus nerve. Considering the patients who do not sufficiently respond to the available drugs, patients for whom the effectiveness of the drugs wanes over time, or have drug-related adverse events, anonpharmacological approach such as bioelectronics might be auseful supplement as an instrument in the successful extension of the therapeutic armamentarium for rheumatic diseases; however, there is a great need for further studies and the development of novel therapeutic strategies in the field of neuroimmunology.

Stimulation of the vagus nerve as a therapeutic principle. German Version

Modulation of the parasympathetic tone leads to extensive physiological reactions at several levels, including the decreased production of proinflammatory cytokines. Many studies have demonstrated that chronic inflammatory diseases are associated with reduced parasympathetic and increased sympathetic activities. Moreover, it was demonstrated that a low parasympathetic and a high sympathetic activity in patients with rheumatoid arthritis (RA) predicts apoor therapeutic response to anti-tumor necrosis factor (TNF) treatment compared to RA patients with amore balanced autonomic nervous system. The autonomic equilibrium could be restored by electrical stimulation of the vagus nerve. Considering the patients who do not sufficiently respond to the available drugs, patients for whom the effectiveness of the drugs wanes over time, or have drug-related adverse events, anonpharmacological approach such as bioelectronics might be auseful supplement as an instrument in the successful extension of the therapeutic armamentarium for rheumatic diseases; however, there is a great need for further studies and the development of novel therapeutic strategies in the field of neuroimmunology.

Serologic Response and Safety after a Third Dose of the COVID-19 BNT162b2 Vaccine in Patients with Inflammatory Bowel Diseases.

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Multiple Orocutaneous Extraintestinal Manifestations in Ulcerative Colitis Patient: Complete Response to Ustekinumab.

Pyostomatitis vegetans (PV) is characterized by exophytic-erythematous pustules with superficial erosions of the oral mucosa, while pyoderma gangrenosum (PG) is a rare skin disorder characterized by the development of painful and deeply ulcerated necrotic areas.1 The diagnosis of PV and PG is based on clinical features while histology is unspecific and not always required.2 We report a case of a 73-year-old woman with steroid-dependent, long-standing pancolonic ulcerative colitis (UC) previously treated with azathioprine and naïve to biologics. She was admitted to hospital for sepsis (fever 39 °C, white blood cell count 18 000, C-reactive protein >200 mg/dL, procalcitonin 0.75 ng/mL) and moderate UC relapse (partial Mayo score 10, Mayo endoscopic subscore 1) with multiple painful, ulcerated, vegetative and purulent lesions in the oral cavity and skin (leg and sacral regions) (Figure 1). ... Intravenous (IV) piperacillin-tazobactam was started and sepsis resolved after 3 days. After dermatological assessment a diagnosis of multiple PG and oral PV was made, IV methylprednisolone 60 mg/d was started. Remission of intestinal symptoms and improvement of orocutaneous lesions were observed until steroid tapering, when orocutaneous lesions worsened. Due to the age of the patient and the recent septic event, anti-tumor necrosis factor (TNF) treatment was considered not indicated and IV ustekinumab 390 mg was started followed by a maintenance regimen with 90 mg every 8 weeks. Complete healing of the orocutaneous lesions and clinical and biochemical remission (partial Mayo score 0, C-reactive protein normalization, fecal calprotectin <150 µg/g) was obtained by the end of induction and maintained off of steroids during the following 10 months.

Evaluation of HLA-B27 frequency in patients with ankylosing spondylitis, and its relationship with clinical symptoms in Khuzestan province

Introduction: Ankylosing spondylitis (AS) is an autoimmune disease, which causes mild to severe clinical symptoms in patients. Several inherited and acquired factors are involved in the pathogenesis of the disease. Human leukocyte antigen B27 (HLA-B27) is one of the factors, whose expression affects patients’ susceptibility to AS. Objectives: In this study, we evaluated HLA-B27 frequency in AS patients of Khuzestan province of Iran. Patients and Methods: The study population (N=114) including patients with AS. Patients were examined and confirmed by a rheumatologist based on New York modified criteria. Clinical information was extracted from patients’ documents. Furthermore, general characteristics of the patients and several clinical variables (physio-pathological, self-report, and imaging) were taken into consideration. Results: The results showed that 62.3% of the patients were HLA-B27 positive, while 37.7% of which were HLA-B27 negative. This difference was statistically significant (P &lt;0.05). The disease duration was shown to be almost equal in both groups (i.e., HLA-B27 positive and HLA-B27 negative). According to the results, various clinical symptoms (like ocular complications and peripheral arthritis) were observed in patients, and the complications of which were higher in HLA-B27 negative patients compared to HLA-B27 positive ones (P &lt;0.05). Besides, it was seen that the male patients have shown a higher physio-pathological (using polymerase chain reaction [PCR] technique) report for positive HLA-B27 and a higher magnetic resonance imaging involvement compared with females, whereas the women showed higher disease activity score i.e., higher mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) value. Conclusion: For the AS patients, negative HLA-B27 cases show more progressive involvement sacroiliac joints compared with the positive HLA-B27 cases. More importantly, of hundred percent of patients who responded to anti-tumor necrosis factor (TNF) treatment, 52.6% were positive for the HLA-B27 antigen, and 47.4% were negative for the HLA-B27 antigen. Overall, it can be said that HLA-B27 lonely is not involved in the pathogenesis of AS and environmental factors should be investigated and involved in the disease development.

Suboptimal response to tumor necrosis factor antagonists in inflammatory bowel disease in Latin America: EXPLORE LATAM study

ObjectiveData on anti-tumor necrosis factor (anti-TNF) treatment and suboptimal response (SOR) among patients with inflammatory bowel diseases (IBD) in Latin America (LATAM) are scarce. This study evaluated the incidence and indicators of SOR to anti-TNF therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) from Argentina, Colombia and Mexico. Patients and methodsWe performed retrospective analysis of data from LATAM patients of the EXPLORE study (NCT03090139) including adult patients with IBD who initiated anti-TNF therapy between March 2010 to March 2015. The cumulative incidence of SOR to first-line anti-TNF therapy was assessed. A physician survey to assess barriers to anti-TNF therapies was also carried out. ResultsWe included 185 IBD patients (UC/CD: 99/86) treated with first-line anti-TNF from Argentina (38 UC; 40 CD), Colombia (21 UC; 25 CD) and Mexico (40 UC; 21 CD). 36.4% of patients with UC and 46.5% of patients with CD experienced SOR to anti-TNF therapy during the median (interquartile range) observational period: 49.0 months (37.2–60.1) in UC, and 50.0 months (40.9–60.1) in CD. The most common indicator of SOR among patients was augmentation of non-biologic therapy (UC: 41.7%; CD: 35.0%). Affordability and late referral to IBD specialist care centers were the most common barriers to anti-TNF therapies. ConclusionsSOR to anti-TNF therapy was common in LATAM IBD patients, where augmentation with non-biologic therapy represented the most frequent indicator of SOR across indications. Our findings contribute to the current evidence on the unmet needs associated with anti-TNF in LATAM.