Anti-tumor Necrosis Factor Treatment Research Articles

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.

Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn's Disease.

Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab). We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization. Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14). LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.

Efficacy of vedolizumab and ustekinumab in pediatric-onset inflammatory bowel disease: A real-world multicenter study.

Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively. The primary outcome was CFR at Week 14 (W14). Twenty-five patients (9 CD, 16 UC) and 33 patients (28 CD, 5 UC) were started on vedolizumab and ustekinumab respectively between 2016 and 2021. All were previously treated with antitumor necrosis factor (TNF). The median time from diagnosis to treatment initiation was 21.0 (12.0-44.0) and 42.0 (22.0-73.5) months for vedolizumab and ustekinumab respectively. Among vedolizumab-treated patients, 36% were in CFR at W14, including 22% in CD and 44% in UC. At W52, 56% were in CFR, including 33% in CD and 69% in UC. Among ustekinumab-treated patients, 49% were in CFR at W14, including 54% in CD and 20% in UC. At W52, 55% were in CFR, including 57% in CD and 40% in UC. There was a significant increase in median growth velocity between W0 and W52 of +2 SD in vedolizumab-treated patients (p = 0.0002). Four adverse events were reported during vedolizumab treatment, none for ustekinumab-treated patients. Vedolizumab and ustekinumab appear to be effective in inducing and maintaining CFR in pediatric-onset IBD. Randomized controlled trials are needed to confirm these results.

Focusing on the Key Factors in the Treatment of Pediatric Crohn's Disease: A Re-Examination of the Relationship Between Body Mass Index and Antitumor Necrosis Factor Treatment Response.

Focusing on the Key Factors in the Treatment of Pediatric Crohn's Disease: A Re-Examination of the Relationship Between Body Mass Index and Antitumor Necrosis Factor Treatment Response.

Comparing Point-of-Care Technology to ELISA Testing for Infliximab and Adalimumab Levels in Adult Inflammatory Bowel Disease Patients: A Prospective Pilot Study.

Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments for anti-TNF drugs. However, several challenges currently impede the widespread adoption of TDM in clinical practice, particularly addressing the delay between sample collection and result availability. To overcome this limitation, the use of point-of-care technology tests (POCTs) is a potential solution. Point-of-care technology tests are medical diagnostic tests performed at the site of patient care to provide immediate results, allowing for quicker decision-making and treatment. The current standard of care (SOC) for drug level measurement relies on the enzyme-linked immunosorbent assay (ELISA), a method that is time-consuming and requires specialized personnel. This study aims to evaluate a novel, user-friendly, and efficient POCT method (ProciseDx Inc.) and compare its performance with the SOC ELISA in assessing infliximab and adalimumab levels in blood samples from IBD patients. Methods: In this prospective, single-center study, we collected blood samples from IBD patients, both CD and UC, receiving infliximab (87 IBD patients; 50% UC and 50% CD) or adalimumab (60 patients; 14% UC and 48% CD) and we analyzed the blood's drugs levels using both the ProciseDx Analyzer POC and the SOC ELISA. We examined the correlation between the two methods using statistical analyses, including the Deming regression test. Additionally, we assessed the ease of use, turnaround time, and overall practicality of the POCT in a clinical setting. Results: The ProciseDx test demonstrated a strong correlation with the SOC ELISA for measuring both infliximab and adalimumab levels. In particular, the overall correlation between the ProciseDx POCT and the ELISA assessments showed an r coefficient of 0.83 with an R squared value of 0.691 (95% CI 0.717-0.902) for IFX measurements, and an r coefficient of 0.85 with an R squared value of 0.739 (95% CI 0.720-0.930). Conclusions: the ProciseDx POC test offers significantly faster turnaround times and is more straightforward to use, making it a viable alternative for routine clinical monitoring. Despite its promising potential, further refinement and validation of the ProciseDx test are necessary to ensure its effectiveness across diverse patient populations and clinical settings. Future research should focus on optimizing the POC tests' performance and evaluating its long-term impact on IBD management.

Identifying genetic variants that influence the abundance of cell states in single-cell data.

Disease risk alleles influence the composition of cells present in the body, but modeling genetic effects on the cell states revealed by single-cell profiling is difficult because variant-associated states may reflect diverse combinations of the profiled cell features that are challenging to predefine. We introduce Genotype-Neighborhood Associations (GeNA), a statistical tool to identify cell-state abundance quantitative trait loci (csaQTLs) in high-dimensional single-cell datasets. Instead of testing associations to predefined cell states, GeNA flexibly identifies the cell states whose abundance is most associated with genetic variants. In a genome-wide survey of single-cell RNA sequencing peripheral blood profiling from 969 individuals, GeNA identifies five independent loci associated with shifts in the relative abundance of immune cell states. For example, rs3003-T (P = 1.96 × 10-11) associates with increased abundance of natural killer cells expressing tumor necrosis factor response programs. This csaQTL colocalizes with increased risk for psoriasis, an autoimmune disease that responds to anti-tumor necrosis factor treatments. Flexibly characterizing csaQTLs for granular cell states may help illuminate how genetic background alters cellular composition to confer disease risk.

Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination.

Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment. We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs. Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti-TNF-treated patients, especially in the elderly. The reduced short- and long-term IgG (1) levels in anti-TNF-treated patients correlated with diminished functional activity and an increased risk for the development of COVID-19. The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.

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% to 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 guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2). Presenting real-world effectiveness data for darvadstrocel in a Spanish population. Observational retrospective cohort study with prospective data gathering. The study was conducted at 14 institutions in Spain. From November 2019 to April 2022, all patients (n = 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; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery. Darvadstrocel treatment. Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, 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 nature of the study. 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, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract . ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco ).

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.

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.

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.

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.

Study of thyroid disorders in ankylosing spondylitis patients on anti-tumor necrosis factor treatment

Abstract: BACKGROUND: Ankylosing spondylitis (AS) is a systemic rheumatic disease characterized mainly by involvement of sacroiliac joints and axial skeleton. Tumor necrosis factor-alpha (TNF-α) inhibitors are biologic agents which are Food and Drug Administration approved to treat AS and also act as a key factor in the treatment of autoimmune thyroid disease. OBJECTIVE: This study aimed to evaluate the thyroid gland disorders (functions and thyroid autoantibodies) in AS patients on anti-TNF-α biologics and their relation to disease activity. PATIENTS AND METHODS: This comparative cross-sectional study included 75 AS patients classified into two groups: Group I: treated with NSAIDs (n = 30) and Group II: treated with anti-TNF-α biologics (n = 45). Thyroid function tests, thyroid autoantibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and human leukocytic antigen B27 were measured. AS disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) scores. Thyroid ultrasonography was used to detect any thyroid gland nodularity and echogenicity. RESULTS: There were significant differences between both groups regarding BASDAI (P = 0.005), CRP (P = 0.005), thyroid-stimulating hormone (TSH) (P = 0.001), and anti-thyroid peroxidase (anti-TPO) (P = 0.007). A significant difference was found regarding the thyroid status, with more normal thyroid and more hyperthyroid patients in the anti-TNF-treated group (P = 0.003). There were statistically significant positive correlations between BASDAI and CRP (P = 0.007), TSH (P = 0.004), and thyroid anti-TPO antibody (P = 0.008) in the anti-TNF-treated patients. By ultrasound examination of the thyroid gland, 75.6% of the anti-TNF group had normal thyroid gland compared to 56.6% of the other group, and the reported nodules were mostly of benign TIRADS classification. Comparing different subgroups of thyroid nodularity with different treatment regimens revealed significant differences in BASDAI and different laboratory investigations in favor of the anti-TNF-treated patients. CONCLUSION: From this cohort study, we can conclude that thyroid autoimmune disease and thyroid nodules in AS patients can be controlled by treatment with anti-TNF-α biologic drugs better than NSAIDs alone.

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.