Anti-tumor Necrosis Factor Therapy Research Articles

Synovial Inflammatory Pathways Characterize Anti-TNF-Responsive Rheumatoid Arthritis Patients.

This study was undertaken to understand the mechanistic basis of response to anti-tumor necrosis factor (anti-TNF) therapies and to determine whether transcriptomic changes in the synovium are reflected in peripheral protein markers. Synovial tissue from 46 rheumatoid arthritis (RA) patients was profiled with RNA sequencing before and 12 weeks after treatment with anti-TNF therapies. Pathway and gene signature analyses were performed on RNA expression profiles of synovial biopsies to identify mechanisms that could discriminate among patients with a good response, a moderate response, or no response, according to the American College of Rheumatology (ACR)/EULAR response criteria. Serum proteins encoded by synovial genes that were differentially expressed between ACR/EULAR response groups were measured in the same patients. Gene signatures predicted which patients would have good responses, and pathway analysis identified elevated immune pathways, including chemokine signaling, Th1/Th2 cell differentiation, and Toll-like receptor signaling, uniquely in good responders. These inflammatory pathways were correspondingly down-modulated by anti-TNF therapy only in good responders. Based on cell signature analysis, lymphocyte, myeloid, and fibroblast cell populations were elevated in good responders relative to nonresponders, consistent with the increased inflammatory pathways. Cell signatures that decreased following anti-TNF treatment were predominately associated with lymphocytes, and fewer were associated with myeloid and fibroblast populations. Following anti-TNF treatment, and only in good responders, several peripheral inflammatory proteins decreased in a manner that was consistent with corresponding synovial gene changes. Collectively, these data suggest that RA patients with robust responses to anti-TNF therapies are characterized at baseline by immune pathway activation, which decreases following anti-TNF treatment. Understanding mechanisms that define patient responsiveness to anti-TNF treatment may assist in development of predictive markers of patient response and earlier treatment options.

Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: a Report from Saudi Arabia.

Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5years (4-26years). The clinical presentation was before the age of 5months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer.

Neurosarcoidosis: Phenotypes, Approach to Diagnosis and Treatment.

The aim of this review is to provide an update of clinical presentation, diagnosis, differential diagnoses, and treatment according to recent evidence. Neurosarcoidosis remains a diagnosis of exclusion, with infectious and malignant etiologies recognized as important mimickers. Corticosteroids remain as first-line therapy. In recent years, however, studies have demonstrated the effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in the treatment of neurosarcoidosis, leading to improved outcomes. Neurosarcoidosis is a granulomatous disease with protean manifestations that may affect any part of the central and peripheral nervous system. It has many mimickers, and potentially devastating complications necessitating long-term follow-up. Early initiation of treatment, particularly with anti-TNF therapy, may lead to better outcomes and fewer relapses. There is an unmet need for randomized controlled trials that provide robust data to guide therapy and the long-term management of neurosarcoidosis patients.

Use of Vedolizumab in Inflammatory Bowel Disease: A Single-Center Experience.

Vedolizumab, which is a monoclonal antibody that selectively binds to α4β7 integrin in the gastrointestinal system, may be an effective and safe treatment alternative in those with anti-tumor necrosis factor-resistant inflammatory bowel disease. Patients administered vedolizumab due to anti-tumor necrosis factor resistant or anti-tumor necrosis factor side effects between August 2017 and November 2020 were included in the study. Crohn's patients were evaluated using the Harvey-Bradshaw index and Simple Endoscopic Score for Crohn's Disease, whereas ulcerative colitis patients were evaluated with the Partial Mayo Score Index and Rachmilewitz score. All patients were followed up for 3 months and their blood samples were taken every 3 months. Hemoglobin, white blood cell, leukocyte, lymphocyte, and platelet counts of the patients were performed. Albumin, C-reactive protein, and erythrocye sedimentation rate values were recorded. The side effect profile for vedolizumab was evaluated for all patients. Among the side effects, arthralgia and flu-like symptoms were observed. A total of 48 patients (18 ulcerative colitis and 30 Crohn's disease) were included in the study. Vedolizumab therapy was initi- ated in the patients due to anti-tumor necrosis factor resistance (17 ulcerative colitis and 26 Crohn's disease) or anti-tumor necrosis factor side effects (1 ulcerative colitis and 4 Crohn's disease). A total of 30 (63%) patients, including 15 (83%) ulcerative colitis and 15 (50%) Crohn's disease, responded to treatment (both response and remission). The mean duration of response to treatment was 4.5 ± 1.5 months. A total of 20 (42%) patients in the vedolizumab therapy subgroup (10/10, ulcerative colitis/Crohn's disease) went into remission. The mean Harvey-Bradshaw Index value was 9.8 ± 2.8 in the Crohn's disease patients at the time of initial treatment. The mean Simple Endoscopic Score for Crohn's disease value was 11.2 ± 3.1 at the time of initial treatment. The mean Harvey-Bradshaw Index value was 6.5 ± 3.0 and the mean Simple Endoscopic Score for Crohn's disease value was 4.9 ± 3.6 at 6 months post-treatment. The mean Ulcerative Colitis Endoscopic Index (Rachmilewitz) value was 9.3 ± 1.2 at the time of initial treatment. In addition, the mean Partial Mayo Scoring Index was 6.4 ± 1.5 at the time of initial treatment. The mean Ulcerative Colitis Endoscopic Index (Rachmilewitz) value was 0 (0-6.0), and the mean Partial Mayo Scoring Index was 1.5 (0.3-4.0) at 6 months post-treatment. Vedolizumab therapy is effective in both induction and maintenance of remission in inflammatory bowel disease patients who are resistant to anti-tumor necrosis factor or who can not receive anti-tumor necrosis factor therapy due to side effects. No signifi- cant side effect was observed in the patients during follow-up.

S974 Comparison of Surgical Rates in Biologic Naive Crohn's Disease Patients on Ustekinumab and Vedolizumab

Introduction: Between 25% to 45% of patients with Crohn’s Disease (CD) require surgical treatment of their disease between 5 and 10 years of diagnosis. Anti-tumor necrosis factor (anti-TNF) therapy has been associated with lower surgical rates in IBD. However, the rate of surgical intervention in ustekinumab- and vedolizumab-treated biologic naïve CD to date patients is unknown. We aimed to investigate the effect of ustekinumab and vedolizumab on intestinal resection rates in bio-naïve CD patients. Methods: A commercial database (Explorys Inc, Cleveland, OH) was utilized, which included electronic health record data from 26 major integrated US healthcare systems. We identified bio-naïve CD patients. The primary outcome was to examine the association between anti-tumor necrosis factor (anti-TNF) medications, ustekinumab, and vedolizumab therapy and the rate of bowel resection in bio-naïve CD patients after at least 12 weeks of treatment. Secondary endpoints were factors associated with increased risk of surgical intervention in these bio-naïve CD patients. Results: The database included over 70 million individuals in which we identified 249,300 (0.35%) adult ( >18 years) patients with CD. Among all CD patients, 1.7% received ustekinumab, 2.4% received vedolizumab, and 16% received anti-TNF as first-line biologic therapy. The rate of intestinal resection was lower among ustekinumab-treated compared to vedolizumab-treated bio-naïve CD patients (11.8% vs. 13.9%, p = 0.001). The rate of intestinal resection was higher among vedolizumab-treated compared to anti-TNF-treated bio-naïve CD patients (13.9% vs. 12.5%, p < 0.0001). However, intestinal resection rates did not significantly differ between ustekinumab-treated compared to anti-TNF-treated bio-naïve CD patients (11.8% vs. 12.5%, p = 0.15). Compared to anti-TNF, tobacco smoking, fistulas, and abscesses were more commonly associated with intestinal resection in ustekinumab- and vedolizumab-treated bio-naïve CD patients. Age < 65 years and intestinal fistulas were commonly associated with ustekinumab-treated bio-naïve CD patients compared to vedolizumab. (Figure) Conclusion: In this large cohort of bio-naïve CD patients, the rate of intestinal resection was lower in ustekinumab-treated and anti-TNF treated patients compared to Vedolizumab after at least 12 weeks of therapy. Further prospective studies are needed to compare the effectiveness and safety of first-line Ustekinumab and Vedolizumab therapy in IBD patients (Table). Figure 1.: Comparison of intestinal resection rates in bio-naive CD patients after at least 12 weeks of ustekinumab, vedolizumab, and anti-TNF. Table 1. - Characteristics of biologic naive CD patients requiring intestinal resection after at least 12 weeks of ustekinumab and vedolizumab Factors UstekinumabN = 510 (%) VedolizumabN = 850 (%) Odds ratio (95% confidence interval), P value Age Adults (18-65y) 460 (90%) 710 (84%) 1.81 (1.28-2.55), 0.0007 Seniors ( >65y) 50 (10%) 140 (16%) 0.55 (0.39-0.77), 0.0007 Race White 460 (90%) 760 (89%) 1.08 (0.75-1.56), 0.64 Non-white 50(10%) 90 (11%) 0.91 (0.63-1.32), 0.64 Gender Female 300 (59%) 460 (54%) 1.21 (0.97-1.51), 0.90 Male 210 (41%) 390 (46%) 0.82 (0.66-1.03), 0.90 Clinical characteristics Tobacco user (current and former) 490 (96%) 820 (96%) 0.89 (0.50-1.59), 0.71 Clostridium difficile infection 70 (14%) 150 (18%) 0.74 (0.54-1.01), 0.05 Small bowel obstruction 10 (2%) 30 (4%) 054 (0.26-1.12), 0.10 Fistula of intestine 230 (45%) 330 (38%) 1.29 (1.03-1.61), 0.02 Anorectal fistula 150 (20%) 230 (27%) 1.12 (0.88-1.43), 0.34 Perianal abscess 100 (20%) 140 (16%) 1.23 (0.93-1.64), 0.14 Anorectal abscess 80 (16%) 130 (15%) 1.03 (0.76-1.39), 0.84 Neoplasm of colon 70 (14%) 160 (19%) 0.68 (0.54-0.93), 0.01 Malignant neoplasm of colon 10 (2%) 30 (4%) 0.54 (0.26-1.12), 0.10

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BackgroundSome patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD.MethodsThis prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response.ResultsThe majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR.ConclusionsMost patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study.

BACKGROUNDA gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability.AIMTo assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.METHODSUCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC. Assessments were performed during patients’ routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.RESULTSFrom 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire–9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41; P = 0.018). Significant changes from baseline to weeks 8 and 52 were observed in disability, HRQoL, and fatigue. Meaningful improvement was reported in work impairment.CONCLUSIONAt week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.

Investigation of the effects of anti-TNF agents on hemoglobin levels in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by many clinical features. Anemia is 1 of the most frequent complications and/or extraintestinal manifestations of IBD. There are conflicting data regarding the relationship between changes in hemoglobin levels and disease prevalence in IBD patients with and without antitumor necrosis factor (antiTNF) therapy. In our study, we aimed to investigate the long-term effect of antiTNF agents on anemia in IBD.The records of IBD patients followed-up in our hospital between January 2011 and January 2021 were reviewed retrospectively. Demographic, clinical, endoscopic, radiological and medical treatment data of the patients were recorded. Complete blood count and laboratory markers of inflammation and disease activation, were recorded at the beginning and at the first year of treatment in all patients. The data of patients with and without antiTNF therapy were analyzed statistically. A total of 240 IBD patients who met the inclusion criteria were enrolled in the study. The number of patients with and without antiTNF therapy was 102 (42.5%) and 138 (57.5%), respectively. The change in all laboratory parameters between the beginning and the first year of treatment was statistically significant (P < .001) in all IBD patients with and without antiTNF therapy. The change in Hb level after 1 year of treatment was significantly different in patients with antiTNF therapy compared to those without therapy (3.00 ± 1.78 g/dL vs 1.19 ± 1.38 g/dL, P < .001). In the multiple regression analysis, male gender, antiTNF therapy, baseline Hb level and iron therapy were independent significant variables of hematopoietic response. This study showed that with appropriate treatment, hemoglobin levels of IBD patients with and without antiTNF therapy increased within 1 year, and the use of antiTNF agents in the treatment of IBD was an independent variable in correcting anemia.

Validation and update of a prediction model for risk of relapse after cessation of anti-TNF treatment in Crohn's disease.

Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn's disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally validate and update our previously developed prediction model to estimate the risk of relapse after cessation of anti-TNF therapy. We performed a retrospective cohort study in 17 Dutch hospitals. Crohn's disease patients in clinical, biochemical or endoscopic remission were included after anti-TNF cessation. Primary outcome was a relapse necessitating treatment. Discrimination and calibration of the previously developed model were assessed. After external validation, the model was updated. The performance of the updated prediction model was assessed in internal-external validation and by using decision curve analysis. 486 patients were included with a median follow-up of 1.7 years. Relapse rates were 35 and 54% after 1 and 2 years. At external validation, the discriminative ability of the prediction model was equal to that found at the development of the model [c-statistic 0.58 (95% confidence interval (CI) 0.54-0.62)], though the model was not well-calibrated on our cohort [calibration slope: 0.52 (0.28-0.76)]. After an update, a c-statistic of 0.60 (0.58-0.63) and calibration slope of 0.89 (0.69-1.09) were reported in internal-external validation. Our previously developed and updated prediction model for the risk of relapse after cessation of anti-TNF in Crohn's disease shows reasonable performance. The use of the model may support clinical decision-making to optimize patient selection in whom anti-TNF can be withdrawn. Clinical validation is ongoing in a prospective randomized trial.

Biologic DMARDs and targeted synthetic DMARDs and the risk of all-cause mortality in rheumatoid arthritis: A systematic review and meta-analysis.

Background:The aim of this study was to perform a meta-analysis to compare the risk of all-cause mortality between biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and non-b/tsDMARDs involving patients with rheumatoid arthritis (RA).Methods:We performed a systematic review of articles published up to August 2021 using electronic databases. We included studies that reported all-cause mortality in RA patients and compared b/tsDMARDs and non-b/tsDMARDs.Results:We included a total of 77 studies involving 64,428 patients. These comprised 44,227 patients treated with b/tsDMARDs and 20,201 treated with non-b/tsDMARDs. The occurrence of all-cause mortality was the primary outcome. The risk of all-cause mortality between the 2 treatments was not significantly different (relative risk = 1.08; 95% confidence interval = 0.98–1.19). However, subgroup analyses showed significant increase in risks of mortality in anti-TNFs users with RA compared with non-b/tsDMARDs (relative risk = 1.47, 95% confidence interval = 1.02–2.12). No significant differences were found after subgroup analyses based on other molecules involved and study duration.Conclusion:In comparison with non-b/tsDMARDs, our results suggest that antitumor necrosis factor therapy is associated with observed increased risks of mortality and further investigation is needed.

Inefficient Induction of Neutralizing Antibodies against SARS-CoV-2 Variants in Patients with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy after Receiving a Third mRNA Vaccine Dose.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine’s effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose can neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)]. Fifty-six subjects with IBD and 12 healthy subjects were recruited. Ninety percent of patients with IBD (49/56) received biologics and/or immunomodulatory therapy. Twenty-four subjects with IBD did not develop effective neutralizing capability against the Omicron variant. Seventy percent (17/24) of those subjects received anti-tumor necrosis factor therapy [10 = adalimumab, 7 = infliximab], two of which had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and more extensive studies are needed to evaluate optimal immunity.

Case report: Safety and efficacy of adalimumab in treating difficult-to-treat rheumatoid arthritis in a human immunodeficiency virus-positive patient, one year follow-up

Rheumatoid arthritis (RA) is a joint-disabling inflammatory disease associated with the pathology of synovitis. Some patients with RA are difficult to treat, using disease-modifying anti-rheumatic drugs (DMARDs). Biology and targeted synthetic DMARDs (b/tsDMARDs) are options for patients with RA. Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). Adalimumab is an anti-tumor necrosis factor therapy commonly used in patients with RA. However, there are no reports or related data on patients with RA-HIV/AIDS treated with adalimumab are available. In this report, we described the first successful case of a 60-year-old HIV-positive woman with difficult-to-treat RA treated with ADA after being screened for hepatitis virus, latent tuberculosis (LTBI), and other infections. She contracted HIV from sexual exposure while on adalimumab therapy. As the patient was resistant to first-line DMARDs, she continued adalimumab along with the initiation of highly active antiretroviral therapy (HAART). The patient was treated with adalimumab therapy for a year; her CD4+ lymphocyte count was normal, HIV-1 RNA decreased, and no new infections were triggered. The patient achieved clinical remission of RA. In conclusion, adalimumab is a safe option for patients with RA-HIV and may slow the progression of HIV infection. Furthermore, HAART has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.ConclusionsAdalimumab is a safe option for patients with RA-HIV, and may slow down the progression of HIV infection. The HAART therapy has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.

Monotherapy with thiopurines in stricturing Crohn's disease: A real-life experience from low- and middle-income countries.

Stricturing Crohn's disease (CD) is difficult to manage medically with limited treatment options, anti-tumor necrosis factor (TNF) therapy being the first-line therapy. Although thiopurines are also recommended first-line treatment option for maintenance of remission in steroid-dependent CD, evidence on their use in stricturing CD is lacking. We evaluated the efficacy of azathioprine (AZA) in patients with stricturing CD. In thisretrospective cohort study (January 2005 to July 2020), patients with stricturing CD who were managed with AZA as a primary therapy for at least 6months, and had a follow-up of at least 6 months after AZA initiation were included. Disease characteristics, complications, long-term response, and adverse events were noted. One hundred andfifteen patients were included (mean age 33.8±14 years, 67.8% males, median disease duration 98 months [IQR: 60-158], median follow-up duration 60 months [IQR: 50-96]). 46.1% (n=53) patients had significant anemia at presentation, and 73% (n=84) had isolated small bowel involvement. Median dose of AZA was 100 mg (equivalent to 1.5 mg/kg). Median therapy and follow-up duration (after AZA initiation) was 17 (IQR: 9-42) and 33 months (IQR 18-60), respectively. The cumulative probability of maintainingresponse without treatment failure at 1, 2, and 5 years was 73.1%, 40.7%, and 18.5%, respectively. Among patients with AZA failure, 15.6% received methotrexate, 13% received anti-TNFs, and 9.5% underwent surgery. Significant anemia (&lt;10 g/dL) at presentation and steroid dependence predicted AZA failure. 31.3% patients experienced adverse events, commonest being leukopenia (n=29, 25.2%). Azathioprine demonstrated good short-term and modest long-term response rates in patients with stricturing CD.

Comparison of the outcomes between early and late anti-tumor necrosis factor therapy in patients with enthesitis-related subcategory of juvenile idiopathic arthritis: a multi-center study in Southeast Asia

ABSTRACT Background Little is known about the impact of delayed initiation of anti-tumor necrosis factor (TNF) therapy in patients with enthesitis-related arthritis (ERA). Here, we compared the impact of delayed treatment on disease outcomes of ERA patients in Southeast Asia. Research design and methods This retrospective study enrolled 149 ERA patients from Thailand and Singapore. Early (e-aTNF) and late (l-aTNF) treatment groups received anti-TNF therapy starting at ≤6 months and >6 months, respectively, after diagnosis. Outcomes included mean differences in disease activity parameters, Juvenile Spondyloarthritis Disease Activity (JSpADA) score, Juvenile Arthritis Diseases Activity (JADAS)-10 score, and American College of Rheumatology Pediatric (ACR Pedi) criteria, and the frequency of clinically inactive disease and first flare event. Results The mean changes in JSpADA (p = 0.002) and JADAS-10 (p < 0.001) scores over time were significantly higher in the e-aTNF group than in the l-aTNF group. A significantly higher proportion of patients in the e-aTNF group than l-aTNF group satisfied ACR Pedi 100 criteria at 2 years (p = 0.042). All other long-term outcomes were not significantly different between the groups. Conclusions Although early anti-TNF treatment improved disease activity parameters somewhat better than delayed anti-TNF therapy, there was no significant difference in long-term outcomes.

Hotspots and future directions in rheumatoid arthritis-related cardiovascular disease: A scientometric and visualization study from 2001 to 2021 based on Web of Science.

BackgroundThe morbidity and mortality of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) is significantly higher than those in the general population, leading to RA-related CVD has attracted broad attention and numerous articles have been published. However, no study has systematically examined this area from a scientometric perspective. This study aimed to visualize the knowledge structure and identify emerging research trends and potential hotspots in this field.Materials and methodsArticles and reviews on RA-CVD published from 2001 to 2021 were extracted from the Web of Science Core Collection database. CiteSpace and VOSviewer software were used to visualize the knowledge network of countries, institutions, authors, references and keywords in this field. SPSS and Microsoft Excel software were used for curve fitting and correlation analysis.ResultsA total of 2,618 articles and reviews were included. The number of publications about RA-related CVD significantly increased yearly. Publications were mainly concentrated in North America, Europe and East Asia. The United States contributed most with 699 publications, followed by the United Kingdom and Italy. Gross Domestic Product was an important factor affecting scientific output. University of Manchester and Professor Kitas George D. were the most prolific institutions and influential authors, respectively. Journal of Rheumatology was the most productive journal for RA-related CVD research. The research hotspots switched in the order of clinical features (cardiovascular events), mechanism exploration, anti-tumor necrosis factor therapy, risk factors, and antirheumatic drug safety, which can be observed from the keyword analysis and co-cited reference cluster analysis.ConclusionsThis study found that research on RA-related CVD is flourishing. The safety and cardiovascular pharmacological mechanisms of anti-rheumatoid drugs, especially targeted synthetic DMARDs, would be the focus of current research and developmental trends in future research.

Early Initiation of Antitumor Necrosis Factor Therapy Reduces Postoperative Recurrence of Crohn's Disease Following Ileocecal Resection.

Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

Multi-utility of therapeutic drug monitoring in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) treatment targets have progressed over time from clinical response to clinical and endoscopic remission. Several data have shown a positive correlation between serum biologic drug concentrations and favorable therapeutic outcomes. Therapeutic drug monitoring (TDM) has evolved as an important approach for optimizing the use of immunobiologics, especially antitumor necrosis factor therapy, in patients with IBD. The use of TDM is supported by medical societies and IBD experts in different contexts; however, challenges remain due to knowledge gaps that limit the widespread use of it. The aim of this review is to assess the role of TDM in IBD, focusing on the implementation of this strategy in different scenarios and demonstrating the multi-utility aspects of this approach in clinical practice.

Effects of Anti-Tumor Necrosis Factor Therapy on Osteoblastic Activity at Sites of Inflammatory and Structural Lesions in Radiographic Axial Spondyloarthritis: A Prospective Proof-of-Concept Study Using Positron Emission Tomography/Magnetic Resonance Imaging of the Sacroiliac Joints and Spine.

Proof-of-concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18-labeled NaF (18 F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI). Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo 18 F-NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow-up visit 3-6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and 18 F-NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded. Overall, 11 male and 5 female patients (mean age ± SD 38.6 ± 12.0 years) were followed up for a mean duration of 4.6 months (range 3-6). 18 F-NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, 18 F-NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow-up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less 18 F-NaF uptake, compared with baseline. For VCs, 18 F-NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow-up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less 18 F-NaF uptake, compared with baseline. Anti-TNF antibody treatment led to a significant decrease in osteoblastic activity within 3-6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA.

Lymphoma Developing in a Patient With Long-term Antitumor Necrosis Factor Therapy.

Lymphoma Developing in a Patient With Long-term Antitumor Necrosis Factor Therapy.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-ץ-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18–20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50–0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66–0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20–22%] vs. 14% [95% CI 13–16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.