anti-TNF Therapy Research Articles

Pre-defined gene co-expression modules in rheumatoid arthritis transition towards molecular health following anti-TNF therapy.

No reliable biomarkers to predict response to TNF inhibitors (TNFi) in RA patients currently exist. The aims of this study were to replicate changes in gene co-expression modules that were previously reported in response to TNFi therapy in RA; to test if changes in module expression are specific to TNFi therapy; and to determine whether module expression transitions towards a disease-free state in responding patients. Published transcriptomic data from the whole blood of disease-free controls (n = 10) and RA patients, treated with the TNFi adalimumab (n = 70) or methotrexate (n = 85), were studied. Treatment response was assessed using the EULAR response criteria following 3 or 6 months of treatment. Change in transcript expression between pre- and post-treatment was recorded for previously defined modules. Linear mixed models tested whether modular expression after treatment transitioned towards a disease-free state. For 25 of the 27 modules, change in expression between pre- and post-treatment in the adalimumab cohort replicated published findings. Of these 25 modules, six transitioned towards a disease-free state by 3months (P < 0.05), irrespective of clinical response. One module (M3.2), related to inflammation and TNF biology, significantly correlated with response to adalimumab. Similar patterns of modular expression, with reduced magnitude, were observed in the methotrexate cohort. This study provides independent validation of changes in module expression in response to therapy in RA. However, these effects are not specific to TNFi. Further studies are required to determine whether specific modules could assist molecular classification of therapeutic response.

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.

Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy.

BackgroundThe impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated.AimsTo reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy.MethodsNinety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed.ResultsThe 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04–4.44), while low age (HR 4.06, 95% CI 1.07–15.4), a low SMI (HR 4.19, 95% CI 1.01–17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36–13.7).ConclusionThe skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.

MiR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.

MicroRNAs are critical regulators of gene expression controlling cellular processes including inflammation. We explored their role in the pathogenesis of inflammatory bowel disease (IBD) and identified reduced expression of miR-374a-5p in IBD monocytes that correlated with a module of up-regulated genes related to the inflammatory response. Key proinflammatory module genes, including for example TNFα, IL1A, IL6, and OSM, were inversely correlated with miR-374a-5p and were validated in vitro. In colonic biopsies, miR-374a-5p was again reduced in expression and inversely correlated with the same inflammatory module, and its levels predicted subsequent response to anti-TNF therapy. Increased miR-374a-5p expression was shown to control macrophage-driven inflammation by suppressing proinflammatory mediators and to reduce the capacity of monocytes to migrate and activate T cells. Our findings suggest that miR-374a-5p reduction is a central driver of inflammation in IBD, and its therapeutic supplementation could reduce monocyte-driven inflammation in IBD or other immune-mediated diseases.

Inflammation induces pro-NETotic neutrophils via TNFR2 signaling.

Cytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMNs). Here, we describe the development of a subgroup of human PMNs expressing CCR5, termed CCR5+ PMNs. Auto- and paracrine tumor necrosis factor (TNF) signaling increases intracellular neutrophil elastase (ELANE) abundance and induces neutrophil extracellular traps formation (NETosis) in CCR5+ PMNs, and triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, known activators of NETosis. Invivo, we find an increased number of CCR5+ PMNs in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ PMNs. In conclusion, we identify a phenotype of pro-NETotic, CCR5+ PMNs present in inflamed tissue invivo and inducible invitro. These cells may reflect an important component of tissue damage during chronic inflammation and could be of diagnostic value.

TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability

Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive. Using a novel humanized model of experimental colitis, we demonstrate that TNF interfered with the tissue repair program via induction of a soluble natural antagonist of IL-22 (IL-22Ra2; IL-22BP) in the colon and abrogated IL-22/STAT3-mediated mucosal repair during colitis. Furthermore, membrane-bound TNF expressed by T cells perpetuated colonic inflammation, while soluble TNF produced by epithelial cells (IECs) induced IL-22BP expression in colonic dendritic cells (DCs) and dampened IL-22-driven restitution of colonic epithelial functions. Finally, TNF induced IL-22BP expression in human monocyte-derived DCs and levels of IL22-BP correlated with TNF in sera of IBD patients. Thus, our data can explain how anti-TNF therapy induces mucosal healing by increasing IL-22 availability and implicates new therapeutic opportunities for IBD.

Clinical and Epidemiological Aspects of Ankylosing Spondylitis Patients in a Single Center in Baghdad

Ankylosing spondylitis is a chronic inflammatory disease with axial involvement but also may present as a peripheral arthritis and extraarticular manifestations. Objective: To assess clinical aspects of ankylosing spondylitis patients and different associated demographic variables in Baghdad teaching hospital. Patients and methods: A cross-sectional study was carried out in Baghdad teaching hospital which includes 402 patients (≥ 18 years old) with a clinical diagnosis of AS according to Assessment of Spondylo Arthritis International Society for AS were involved in this study from June/2019 to June/2021. Demographic data and disease characteristics, presence of extra-articular manifestations (past and present) and measurement of disease activity was done by BASDAI, erythrocyte sedimentation rate (mm/h) and C-reactive protein (mg/L). In addition, HLAB27 typing was reported. Results: The age of onset for males was 24.87±8.8 and for females25.97±8.6 years, HLA typing HLA-B27 were 49.55% and 35.38% in males and females respectively and the association was found to be statistically significant (P. value =0.031). While family history was reported at 25.82% and 34.33% in males and females correspondingly. 75.07% of males compared to 71.38% of females were treated with Anti TNF therapy. Females had later onset of disease than males with lower percentage of HLA B27 positivity. Recommendation: more comprehensive assessment with advanced diagnostic and treatment standards.

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn's Disease.

Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn’s disease (CD) in clinical practice. However, differential individual response necessitates a therapeutic response assessment of anti-TNF agents in CD patients for optimizing therapeutic strategy. We aimed to predict anti-TNF therapy response in CD patients using transcriptome analyses. Transcriptome analyses were performed using data from the Gene Expression Omnibus, GeneCards, and Human Protein Atlas databases. The significantly mitigated biological functions associated with anti-TNF therapy resistance in CD patients encompassed immune pathways, including Interleukin-17 (IL-17) signaling, cytokine-cytokine receptor interaction, and rheumatoid arthritis. The scores of immune cell markers, including neutrophils, monocytes, and macrophages/monocytes were also significantly decreased in non-responders compared with that measured in anti-TNF therapy responders. The KAT2B gene, associated with IL-17 cytokine mediated neutrophil mobilization and activation, was significantly under-expressed in both tissue and peripheral blood mononuclear cells (PBMCs) in anti-TNF therapy-resistant CD patients. The reduced expression of several pro-inflammatory cytokines due to down-regulated IL-17 signaling, is suggestive of the primary non-response to anti-TNF agents in CD patients. Furthermore, the PBMC KAT2B gene signature may be a promising pre-treatment prognostic biomarker for anti-TNF drug response in CD patients.

Predictor of primary response to antitumor necrosis factor-α therapy for inflammatory bowel disease: a single-center observational study.

It is necessary to find reliable and appropriate predictors of primary response to anti-TNFα therapy (infliximab and adalimumab) in inflammatory bowel disease (IBD) so as to avoid treatment failure and select optimal treatment. The aim of this study is to reveal useful predictors of the response to anti-TNFα treatment from baseline to 2 months after initial administration of anti-TNFα for individual IBD patients using our pharmacokinetic and pharmacodynamic (PK/PD) model at the time of second administration. We retrospectively analyzed 26 IBD patients who received anti-TNFα. In the PK/PD model, inflammation was assumed to be suppressed based on the action of anti-TNFα at the rate constant of Kanti-TNFα (day-1). Kanti-TNFα0 (day-1) is Kanti-TNFα in the absence of anti-TNFα. We expressed inflammation caused by factors not affected by the action of anti-TNFα using the rate constant Kelse (day-1). Using univariate and multivariate linear regressions, we statistically analyzed factors related to the improvement of disease activity index. The significant correlation between Kanti-TNFα0/Kelse and the improvement of disease activity index was shown in Crohn's disease patients (univariate: estimated value 2.4; P = 0.003; and multivariate: 1.8; P = 0.012) and ulcerative colitis patients (univariate: 0.12; P = 0.011), and no other factors were significant. This is the first study to present a useful predictor of primary response to anti-TNFα of individual IBD patients at second administration. The Kanti-TNFα0/Kelse ratio may help to select the optimal therapeutic drug and avoid the improper continuous administration of anti-TNFα in the induction phase.

Comparative effectiveness of second-line biological therapies for ulcerative colitis and Crohn\u2019s disease in patients with prior failure of anti-tumour necrosis factor treatment

BackgroundTherapeutic options for inflammatory bowel disease (IBD) have increased since the introduction of tumour necrosis factor (TNF) inhibitors a few decades ago. However, direct comparisons of the effectiveness of second-line biological agents in patients with ulcerative colitis (UC) and Crohn’s disease (CD) are lacking.MethodsPatients with UC or CD who experienced anti-TNF treatment failure and subsequently used vedolizumab, ustekinumab, or tofacitinib as a second-line drug were retrospectively recruited. The primary outcomes were the clinical remission rate at week 16 and the cumulative relapse rate 48 weeks after receiving induction therapy.ResultsA total of 94 patients with UC or CD experienced anti-TNF treatment failure and received vedolizumab (UC: 37; CD: 28), ustekinumab (CD: 16), or tofacitinib (UC: 13). The clinical remission rates were not significantly different between the vedolizumab and tofacitinib groups in UC patients (56.8% vs. 46.2%, p = 0.509). In CD patients, the clinical remission rates were not significantly different between the vedolizumab and ustekinumab groups (53.6% vs. 50.0%, p = 0.820). Moreover, the cumulative rates of clinical relapse were not significantly different between the vedolizumab and tofacitinib groups in UC patients and between the vedolizumab and ustekinumab groups in CD patients (p = 0.396 and p = 0.692, respectively). Safety profiles were also similar among the treatment groups in both UC and CD patients.ConclusionsAfter prior anti-TNF therapy failure, vedolizumab and tofacitinib in UC patients and vedolizumab and ustekinumab in CD patients were not significantly different in terms of the efficacy in inducing and maintaining a clinical response.

Natural History of New-onset Inflammatory Bowel Disease Among Patients With Multiple Sclerosis.

Lay Summary Patients with MS and IBD were as likely to have stricturing, fistulizing, and extensive IBD as IBD controls. Although MS-IBD patients were less likely to initiate anti-TNF therapy, they did not have worsened risk of progression to surgery on follow-up.

Secukinumab in the treatment for patients with juvenile enthesitis related arthritis non-responsive to anti-TNF treatment according the Juvenile Spondyloarthritis Disease Activity Index.

To review the effectiveness of secukinumab (SEC) in patients with juvenile idiopathic enthesitis related arthritis (ERA), who had partial or no response on anti-TNF therapy. We conducted a retrospective monocentric chart review of patients with ERA, who were treated with SEC, until March 15th 2019. We used the JADAS10 and the Juvenile Spondyloarthritis Disease Activity Index (jspADA) to evaluate response. We analysed the onset of AE and SAE. We analysed 17 patients with ERA. The mean age at the start of the treatment was 19.5 years (SD 4.9, range 13-34 years, median 18.2). The mean disease duration was 6.3 years (SD 3.3, range 2-12 years). The patients received in average 1.9 (SD1.0) different anti-TNF'́s before switching to SEC. SEC was applied at the start of the treatment with 150 mg per dose (n=13, 76.5%) and 300 mg per dose (n=4, 23.5%). The dose of 150 mg was increased in 11 patients (85% of 13) after baseline. The mean follow-up of patients was 18.2 months (SD 7.2) accounting to 25.8 years under exposure to SEC. The jspADA (mean change of -1.3; p<0.001; 95%CI: -1.9 to -0.7) and JADAS10 (mean change of -2.4; p=0.021; 95%CI: -4.5 to -0.4) signi cantly improved between baseline and the 24-month follow-up. There was no serious adverse event observed. In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.

The Impact of Intermediate Antidrug Antibodies to Infliximab and Adalimumab on Clinical Outcomes in Patients with Crohn’s Disease or Ulcerative Colitis

Background: The anti-TNF drugs adalimumab (ADA) and infliximab (IFX) are effective treatments for inflammatory bowel disease (IBD). However, 40% of patients lose response, often due to the development of antibodies-to-ADA (ATA) and antibodies-to-IFX (ATI). While low ATA/ATI titres (&lt;200 ng/mL) are associated with better outcomes and high ATA/ATI titres (&gt;1,000 ng/mL) are associated with poorer outcomes, the significance of intermediate ATA/ATI titres (200–999 ng/mL) is not well understood. This study aims to investigate the impact of intermediate ATA/ATI titres on outcomes in patients with IBD. Methods: A retrospective chart review of 376 patients with IBD was conducted. The primary clinical outcome was persistence on anti-TNF therapy for 1 year after the measurement of ATA/ATI titres. The participants consisted of patients with IBD treated with IFX or ADA at the University of Maryland Medical Center’s Inflammatory Bowel Disease Program between October 2016 and October 2019. Results: Out of 322 patients with low titres, 271 persisted on their original anti-TNF, compared with nine out the 15 patients with intermediate titres (p=0.026) and one out the 10 patients with high titres (p&lt;0.0001). The odds ratio of persistence when comparing intermediate titres to low titres was 0.26 (0.09–0.80), and when comparing high titres to low titres was 0.02 (0.00–0.14). Conclusion: Patients with intermediate titres were more likely to lose response to anti-TNF drugs and require a change in anti-TNF therapy than patients with low titres. Although the sample size of patients with intermediate titres was small, providers should consider dose optimisation of anti-TNF drugs, with or without the addition of an immunosuppressant, when intermediate titres are present.

Oral surveillance and JAK inhibitor safety: the theory of relativity.

The published results of the post-marketing ORAL Surveillance study, which compared the Janus kinase (JAK) inhibitor tofacitinib with anti-TNF therapy in older patients with rheumatoid arthritis who have cardiovascular risk factors, have led to changes in the recommendations for the use of JAK inhibitors. Although new safety signals have emerged for tofacitinib, namely malignancy and cardiovascular disease, it should be noted that these signals are relative to those seen with TNF blockers. The new data further raise our intrigue that venous thromboembolism might be a true risk related to JAK inhibition. Reassuringly, the totality of the findings from this newly published study and the other data collected to date suggest that JAK inhibitors can be used safely at approved doses by many patients with rheumatoid arthritis.

Influence of comorbidities on treatment considerations for first-line biologic prescribing in patients with inflammatory bowel disease in the UK

BackgroundAnti-tumour necrosis factor (anti-TNF) therapies are the most commonly used biologics for inflammatory bowel disease (IBD), but for patients with a comorbidity, newer agents may be a more appropriate treatment...

Transcriptomic and cellular decoding of functional brain connectivity changes reveal regional brain vulnerability to pro- and anti-inflammatory therapies

BackgroundSystemic inflammation induces acute changes in mood, motivation and cognition that closely resemble those observed in depressed individuals. However, the mechanistic pathways linking peripheral inflammation to depression-like psychopathology via intermediate effects on brain function remain incompletely understood. MethodsWe combined data from 30 patients initiating interferon-α treatment for Hepatitis-C and 20 anti-tumour necrosis factor (TNF) therapy for inflammatory arthritis and used resting-state functional magnetic resonance imaging to investigate acute effects of each treatment on regional global brain connectivity (GBC). We leveraged transcriptomic data from the Allen Human Brain Atlas to uncover potential biological and cellular pathways underpinning regional vulnerability to GBC changes induced by each treatment. ResultsInterferon-α and anti-TNF therapies both produced differential small-to-medium sized decreases in regional GBC. However, these were observed within distinct brain regions and the regional patterns of GBC changes induced by each treatment did not correlate suggesting independent underlying processes. Further, the spatial distribution of these differential GBC decreases could be captured by multivariate patterns of constitutive regional expression of genes respectively related to: i) neuroinflammation and glial cells; and ii) glutamatergic neurotransmission and neurons. The extent to which each participant expressed patterns of GBC changes aligning with these patterns of transcriptomic vulnerability also correlated with both acute treatment-induced changes in interleukin-6 (IL-6) and, for Interferon-α, longer-term treatment-associated changes in depressive symptoms. ConclusionsTogether, we present two transcriptomic models separately linking regional vulnerability to the acute effects of interferon-α and anti-TNF treatments on brain function to glial neuroinflammation and glutamatergic neurotransmission. These findings generate hypotheses about two potential brain mechanisms through which bidirectional changes in peripheral inflammation may contribute to the development/resolution of psychopathology.

Risk Factors Leading to Anti-TNF Alpha Therapies in Pediatric Severe Uveitis.

PurposePediatric uveitis is the leading cause of acquired child blindness, due to unremitting inflammation and long-term steroid exposition. Biotherapies with anti-tumor necrosis factor alpha (anti-TNFα) are effective in controlling inflammation for severe pediatric uveitis in recent studies. Major concern of anti-TNFα prescription is the balance between the severity of the disease and side effects of the drug. The aim of the present study is to describe a cohort of children with severe uveitis and to highlight the risk factors for a pejorative development that led to the prescription of anti-TNFα drugs.MethodA retrospective case-control study was carried out on children with uveitis associated with systemic inflammatory disease or idiopathic uveitis, with a minimum follow-up of 5 years. Anti-TNFα-treated patients (case) were studied and compared with patients who were not requiring anti-TNFα (control). Univariate logistic regression analyses were performed to compare both groups and determine the risk factors for anti-TNFα therapy.ResultsSeventy-three cases of pediatric uveitis were included, 13 cases and 60 controls. The risk factors associated with increased odds of anti-TNFα therapy were initial systemic disorder associated with uveitis [OR = 11.22 (1.37–91.85), p = 0.0241), family history of autoimmune diseases [OR = 9.43 (2.27–39.15), p = 0.0020], uveitis diagnosis before the age of 6 [OR = 4.05 (1.16–14.13), p = 0.0284], eye surgery [OR = 26.22 (2.63–261.77), p = 0.0054], ocular complications at the first slit lamp exam [OR = 67.11 (3.78–1191.69), p = 0.0042], low visual acuity at diagnosis (≥0.3 logMAR) [OR = 11.76 (2.91–47.62), p = 0.0005] and especially low binocular acuity at diagnosis (≥0.3 logMAR) [OR = 8.75 (1.93–39.57), p = 0.0048], panuveitis [OR = 9.17 (2.23–37.60), p = 0.0021], having positive ANA [OR = 3.89 (1.07–14.11), p = 0.0391], and positive HLA B27 [OR = 9.43 (2.27–39.16), p = 0.0020].ConclusionThose risk factors could be used to establish a new follow-up and treatment schedule for severe uncontrolled uveitis. This could help to better predict the best time to start anti-TNF therapy.

Earlier Anti-TNF Initiation Leads to Long-term Lower Health Care Utilization in Crohn’s Disease but Not in Ulcerative Colitis

The timing of initiating biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations. We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups. Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery. Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC.

Incidence of and Risk Factors for Paradoxical Psoriasis or Psoriasiform Lesions in Inflammatory Bowel Disease Patients Receiving Anti-TNF Therapy: Systematic Review With Meta-Analysis.

BackgroundParadoxical psoriasis or psoriasiform lesions induced by anti-tumor necrosis factor (anti-TNF) therapies receive increasing attention worldwide. However, no comprehensive meta-analysis investigating the incidence estimates and risk factors for anti-TNF-induced psoriasis is currently available. We aimed to precisely quantify its incidence as well as risk factors in patients with inflammatory bowel disease (IBD).MethodsThis study was registered on PROSPERO database under review registration number CRD42021233695. The electronic databases PubMed, EMBASE, and the Cochrane library were comprehensively searched for observational studies published as full-length papers in English and reporting the incidence and/or predictors for psoriasis or psoriasiform lesions in IBD patients. A random-effects meta-analysis was performed to calculate the pooled incidence. Pooled odds ratio (OR) and 95% confidence interval for potential predictors were combined using a fixed-effects or random-effects model.ResultsIn total, 30 articles comprising 24,547 IBD patients treated by anti-TNF were finally included. The overall pooled incidence of psoriasis and/or psoriasiform lesions following anti-TNF therapy was 6.0% (5.0–7.0%; I 2 = 93.9%), with 6.9% (5.1–8.7%; I 2 = 92.4%) for psoriasiform lesions and 4.6% (3.6–5.6%; I 2 = 93.9%) for psoriasis. Multivariable meta-regression analysis indicated regions and populations that significantly contributed to the heterogeneity. A statistically higher risk for psoriasis or psoriasiform lesions during anti-TNF therapy was observed in female patients (OR 1.46, 1.23–1.73), those who are at a younger age at anti-TNF initiation (OR 1.03, 1.00–1.05), smokers (OR 1.97, 1.56–2.48), ileocolonic Crohn’s disease patients (OR 1.48, 1.03–2.13), and those who are using adalimumab or certolizumab (vs. infliximab) (OR: 1.48 and 2.87 respectively).ConclusionsThe incidence of psoriasis or psoriasiform lesions was not uncommon in IBD patients following anti-TNF therapy. Female, younger age, smoker, ileocolonic Crohn’s disease, and the types of anti-TNF were significantly associated with such risk. These findings may help gastroenterologists to make more individualized decisions and understand the mechanisms of this paradoxical phenomenon.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233695, identifier CRD42021233695.

Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region.

Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5±13.4years, 60% males, median follow-up duration after anti-TNF: 33months [interquartile range: 23-57months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p<0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p=0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.