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A teenage girl presented with fever and altered mental status. MRI showed diffuse leptomeningeal enhancement of the brain and spine. She was diagnosed by a positive cerebrospinal fluid (CSF) culture with tuberculous (TB) meningitis and was started on anti-TB medications and corticosteroids. Her mental status improved, but she was noted to have proximal weakness of the lower extremities. In the course of tapering corticosteroids at week 11 of anti-TB therapy, she became acutely confused and febrile. MRI demonstrated interval development of tuberculomas in the brain and a mass lesion in the thoracic spine causing cord compression. Given the clinical picture was suggestive of a paradoxical reaction, the dose of corticosteroids was increased. Infliximab was added when repeat MRI revealed enlargement of the mass lesion in the spine with worsening cord compression. She was successfully tapered off of corticosteroids. Over several months, the patient's motor function recovered fully, and she returned to ambulating without assistance.

PURPOSE: To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. OBSERVATIONS: A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patients retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. CONCLUSIONS AND IMPORTANCE: This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.

Background Ustekinumab is an interleukin (IL)-12/IL-23 inhibitor for the treatment of moderate-to-severe psoriasis.Objective This real-world study compared ustekinumab and tumor necrosis factor-alpha inhibitors (TNFis) in Chinese moderate-to-severe psoriasis patients.Methods Patient health records of 110 moderate-to-severe psoriasis patients initiating or switching biologics were reviewed, with 31 patients receiving ustekinumab (ustekinumab group) and 79 patients receiving TNFis (TNFi group).Results Compared with TNFi group, psoriasis area and severity index (PASI)-75 response rate at month 6 (M6) were elevated (87.1% versus 65.8%, p = 0.026) in the ustekinumab group, whereas the rates at month 1 (M1) and month 3 (M3) and PASI-90 response rates at M1, M3, and M6 only showed an increasing trend (all p > 0.050) in the ustekinumab group than the TNFi group. By subgroup analyses, ustekinumab (versus TNFi) was more effective in patients with biologics therapy history than those without. Compared with the TNFi group, the ustekinumab group had lower dermatology life quality index scores and higher patient satisfaction scores at M3 and M6 (all p

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine. Etanercept is a Tumor necrosis factor-alpha inhibitor (anti-TNF) that is widely used in the treatment of AS. The most common side effects of etanercept are infection, rash, and injection site reaction. Here, we reported an adverse event probably associated with etanercept. Case Presentation: A 30-year-old male patient with AS initiated etanercept due to uncontrolled back pain despite adequate doses of non-steroidal anti-inflammatory drugs. He developed erectile dysfunction (ED) within 1 month of etanercept treatment. ED disappeared after switching to secukinumab. Conclusion: There is limited data on the potential effects of anti-TNF on sexual function. ED might be a rare side effect of etanercept that resolves upon discontinuation of the drug. Secukinumab might be considered as an option in case of etanerceptinduced ED. Even though ED is not a life-threatening side effect, switching medications could significantly improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development.Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression.Results: Ten compounds and 128 target genes were screened from SC, of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression.Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi.

Purpose: To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. Observations: A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patient's retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. Conclusions and importance: This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.

Background/aim: To investigate the impact of smoking on disease activity, treatment retention, and response in patients with ankylosing spondylitis (AS) treated with their first tumor necrosis factor-a inhibitor (TNFi). Materials and methods: AS patients who started their first TNFi treatment for the active axial disease (BASDAI ≥ 4) from TURKBIO Registry were included. Treatment response of smoker (current and ex-smokers) and nonsmoker (never smoker) patients were primarily evaluated as achievement of BASDAI50 or improvement in BASDAI at least 20 mm at 3 months and 6 months compared to baseline. Results: There were 322 patients with AS (60% male, 59% smoker, mean age: 38.3 years). The median follow-up time was 2.8 years (Q1-Q3: 1.3-3.8), and disease duration was 3.5 years (Q1-Q3: 0.7-8.2). Smokers had male predominance (p < 0.001), lower ESR (p = 0.03), higher BASDAI (p = 0.02), BASFI (p = 0.05), HAQ-AS (p = 0.007), and ASDAS-CRP (p = 0.04) compared with nonsmokers at baseline. In the multivariate analysis, male gender [OR 2.7 (95%CI 1.4-5), p = 0.002], and concomitant conventional synthetic disease-modifying antirheumatic drug use [OR 2.4 (95%CI 1.1-5.2), p = 0.03] were associated with better treatment response. There was an association of male gender [HR 2.4 (95%CI 1.6-3.7), p < 0.001], older age (≥30years) [HR 1.8 (95%CI 1.1-2.8), p = 0.01], and response to treatment [HR 1.8 (95%CI 1.2-2.9), p = 0.008] with better treatment retention. No impact of smoking status was found on treatment retention and response in univariate and multivariate analyses. Conclusion: This study suggested that smoking was associated with poorer patient-reported outcomes in biologic naïve AS patients initiating their first TNFi treatment, but it had no impact on the TNFi treatment response and retention rate. [ABSTRACT FROM AUTHOR]

Abstract Background Titin phosphorylation contributes to left ventricular (LV) diastolic dysfunction. The independent effects of inflammation on the molecular pathways that regulate titin phosphorylation are unclear. Methods We investigated the effects of collagen-induced inflammation and subsequent tumor necrosis factor-α (TNF-α) inhibition on mRNA expression of genes involved in regulating titin phosphorylation in 70 Sprague-Dawley rats. LV diastolic function was assessed with echocardiography. Circulating inflammatory markers were quantified by enzyme-linked immunosorbent assay and relative LV gene expression was assessed by Taqman® polymerase chain reaction. Differences in normally distributed variables between the groups were determined by two-way analysis of variance (ANOVA), followed by Tukey post-hoc tests. For non-normally distributed variables, group differences were determined by Kruskal–Wallis tests. Results Collagen inoculation increased LV relative mRNA expression of vascular cell adhesion molecule 1 (VCAM1), pentraxin 3 (PTX3), and inducible nitric oxide synthase (iNOS) compared to controls, indicating local microvascular inflammation. Collagen inoculation decreased soluble guanylate cyclase alpha-2 (sGCα2) and soluble guanylate cyclase beta-2 (sGCβ2) expression, suggesting downregulation of nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling. Inhibiting TNF-α prevented collagen-induced changes in VCAM1, iNOS, sGCα2 and sGCβ2 expression. Collagen inoculation increased protein phosphatase 5 (PP5) expression. Like LV diastolic dysfunction, increased PP5 expression was not prevented by TNF-α inhibition. Conclusion Inflammation-induced LV diastolic dysfunction may be mediated by a TNF-α-independent increase in PP5 expression and dephosphorylation of the N2-Bus stretch element of titin, rather than by TNF-α-induced downregulation of NO-sGC-cGMP pathway-dependent titin phosphorylation. The steady rise in number of patients with inflammation-induced diastolic dysfunction, coupled with low success rates of current therapies warrants a better understanding of the systemic signals and molecular pathways responsible for decreased titin phosphorylation in development of LV diastolic dysfunction. The therapeutic potential of inhibiting PP5 upregulation in LV diastolic dysfunction requires investigation.

Tumor necrosis factor-alpha (TNFα) may promote neuroinflammation prompting tinnitus. This retrospective cohort study evaluated whether anti-TNFα therapy influences incident tinnitus risk among adults with autoimmune disorders and no baseline tinnitus selected from a US electronic health records database (Eversana; 1 January 2010–27 January 2022). Patients with anti-TNFα had ≥90-day history pre-index (first autoimmune disorder diagnosis) and ≥180-day follow-up post-index. Random samples (n = 25,000) of autoimmune patients without anti-TNFα were selected for comparisons. Tinnitus incidence was compared among patients with or without anti-TNFα therapy, overall and among at-risk age groups or by anti-TNFα category. High-dimensionality propensity score (hdPS) matching was used to adjust for baseline confounders. Compared with patients with no anti-TNFα, anti-TNFα was not associated with tinnitus risk overall (hdPS-matched HR [95% CI]: 1.06 [0.85, 1.33]), or between groups stratified by age (30–50 years: 1 [0.68, 1.48]; 51–70 years: 1.18 [0.89, 1.56]) or anti-TNFα category (monoclonal antibody vs. fusion protein: 0.91 [0.59, 1.41]). Anti-TNFα was not associated with tinnitus risk among those treated for ≥6 months (hdPS-matched HR [95% CI]: 0.96 [0.69, 1.32]) or ≥12 (1.03 [0.71, 1.5]), or those with RA (1.16 [0.88, 1.53]). Thus, in this US cohort study, anti-TNFα therapy was not associated with tinnitus incidence among patients with autoimmune disorders. [ABSTRACT FROM AUTHOR]

Background: Titin phosphorylation contributes to left ventricular (LV) diastolic dysfunction. The independent effects of inflammation on the molecular pathways that regulate titin phosphorylation are unclear. Methods: We investigated the effects of collagen-induced inflammation and subsequent tumor necrosis factor-α (TNF-α) inhibition on mRNA expression of genes involved in regulating titin phosphorylation in 70 Sprague-Dawley rats. LV diastolic function was assessed with echocardiography. Circulating inflammatory markers were quantified by enzyme-linked immunosorbent assay and relative LV gene expression was assessed by Taqman® polymerase chain reaction. Differences in normally distributed variables between the groups were determined by two-way analysis of variance (ANOVA), followed by Tukey post-hoc tests. For non-normally distributed variables, group differences were determined by Kruskal–Wallis tests. Results: Collagen inoculation increased LV relative mRNA expression of vascular cell adhesion molecule 1 (VCAM1), pentraxin 3 (PTX3), and inducible nitric oxide synthase (iNOS) compared to controls, indicating local microvascular inflammation. Collagen inoculation decreased soluble guanylate cyclase alpha-2 (sGCα2) and soluble guanylate cyclase beta-2 (sGCβ2) expression, suggesting downregulation of nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling. Inhibiting TNF-α prevented collagen-induced changes in VCAM1, iNOS, sGCα2 and sGCβ2 expression. Collagen inoculation increased protein phosphatase 5 (PP5) expression. Like LV diastolic dysfunction, increased PP5 expression was not prevented by TNF-α inhibition. Conclusion: Inflammation-induced LV diastolic dysfunction may be mediated by a TNF-α-independent increase in PP5 expression and dephosphorylation of the N2-Bus stretch element of titin, rather than by TNF-α-induced downregulation of NO-sGC-cGMP pathway-dependent titin phosphorylation. The steady rise in number of patients with inflammation-induced diastolic dysfunction, coupled with low success rates of current therapies warrants a better understanding of the systemic signals and molecular pathways responsible for decreased titin phosphorylation in development of LV diastolic dysfunction. The therapeutic potential of inhibiting PP5 upregulation in LV diastolic dysfunction requires investigation. [ABSTRACT FROM AUTHOR]

Background/Aims: Many patients with Crohn’s disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery. Methods: This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups. Results: In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011). Conclusions: Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended.

Refractory recurrent aphthous stomatitis (RRAS) manifests as severe ulcerative lesions of the oral mucosa with poor healing and a poor response to conventional therapy, with or without systemic diseases. Its treatment remains a clinical challenge owing to the lack of effective therapies. Recently, biologics have emerged as promising targeted therapies for RRAS. The biologics targeting specific inflammatory pathways involved in the pathogenesis of RRAS, including tumor necrosis factor-alpha inhibitors and interleukin inhibitors, offer a more precise and promising therapeutic approach for RRAS. These targeted therapies have been shown to promote healing and decrease recurrence frequency in, and improve the quality of life of patients with RRAS. Herein, the types and mechanisms of biologics currently used to treat RRAS have been reviewed; furthermore, the dose, duration, therapeutic efficacy, and adverse effects of RRAS with or without certain associated systemic diseases, and the current problems and future directions have been discussed. [ABSTRACT FROM AUTHOR]

BackgroundTumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis.ObjectiveTo better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis.MethodsSystematic review of published cases of TNF-α inhibitor-induced psoriasis.ResultsWe identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF-α therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin-directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%).LimitationsRetrospective review that relies on case reports and series.ConclusionWhile TNF-α inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF-α inhibitor-induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin-directed therapy is a reasonable initial strategy except in severe cases.

Here, we report two cases of cutaneous adverse effects possibly induced by the use of tumor necrosis factor-alpha (TNF-α) inhibitors. The first case presented alopecia areata (AA) and atopic dermatitis (AD) that developed during the treatment of ulcerative colitis using infliximab; the other case presented urticaria and AD that developed during the treatment of rheumatoid arthritis using etanercept. AA, AD, and urticaria are relatively common skin diseases; however, they are not well known as adverse effects of TNF-α inhibitors. Although immunological studies were not performed, the clinical courses suggested that these skin disorders might have developed as a result of an immune four-way imbalance in T helper 1 (Th1), Th2, Th17, and regulatory T cells by the administration of TNF-α inhibitors.

Background/Aims: Many patients with Crohn’s disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery. Methods: This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups. Results: In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011). Conclusions: Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended. [ABSTRACT FROM AUTHOR]

Background: Ustekinumab is an interleukin (IL)-12/IL-23 inhibitor for the treatment of moderate-to-severe psoriasis., Objective: This real-world study compared ustekinumab and tumor necrosis factor-alpha inhibitors (TNFis) in Chinese moderate-to-severe psoriasis patients., Methods: Patient health records of 110 moderate-to-severe psoriasis patients initiating or switching biologics were reviewed, with 31 patients receiving ustekinumab (ustekinumab group) and 79 patients receiving TNFis (TNFi group)., Results: Compared with TNFi group, psoriasis area and severity index (PASI)-75 response rate at month 6 (M6) were elevated (87.1% versus 65.8%, p  = 0.026) in the ustekinumab group, whereas the rates at month 1 (M1) and month 3 (M3) and PASI-90 response rates at M1, M3, and M6 only showed an increasing trend (all p  > 0.050) in the ustekinumab group than the TNFi group. By subgroup analyses, ustekinumab (versus TNFi) was more effective in patients with biologics therapy history than those without. Compared with the TNFi group, the ustekinumab group had lower dermatology life quality index scores and higher patient satisfaction scores at M3 and M6 (all p  < 0.050)., Conclusion: Chinese moderate-to-severe psoriasis patients treated with ustekinumab have a better treatment response at 6 months with improved quality of life and patient satisfaction after 3-6 months of treatment when compared to TNFi.

Cytokine blocking therapies have revolutionized the management of psoriasis and atopic dermatitis but can lead to the development of paradoxic psoriasis (PP). Patients treated with biologics should be closely monitored for the development of PP and other paradoxical eruptions (including inflammatory joint disease, inflammatory bowel disease, eczematous eruptions, lupus like eruptions, sarcoidal eruptions, and others) and occasionally the development of cutaneous T-cell lymphoma. Further understanding the immunologic mechanism of these processes will ultimately drive our understanding of and ability to predict and manage PPs., Competing Interests: Disclosure There are no funding sources. M. Abdelghaffar, S. Kottilil, and M.J. Murphy have nothing to disclose. J.M. Cohen serves on a data and safety monitoring board for Advarra and has received consulting fees from Novartis. W. Damsky has received research support from Pfizer, United States, Advanced Cell Diagnostics/Bio-techne, AbbVie, United States, Incyte, United States, and Bristol-Myers Squibb, United States; receives consulting fees from Eli Lilly, TWI Biotechnology, Incyte, Epiarx Diagnostics, Bristol Myers Squibb, and Boehringer Ingelheim; and receives licensing fees from EMD/Millipore/Sigma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM. This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events. In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127–5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170–0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041–6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039–8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539–11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications. TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking.Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA–WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP–RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α.Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis.Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.

Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking. Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA–WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP–RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α. Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis. Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA. [ABSTRACT FROM AUTHOR]

Here, we report two cases of cutaneous adverse effects possibly induced by the use of tumor necrosis factor-alpha (TNF-α) inhibitors. The first case presented alopecia areata (AA) and atopic dermatitis (AD) that developed during the treatment of ulcerative colitis using infliximab; the other case presented urticaria and AD that developed during the treatment of rheumatoid arthritis using etanercept. AA, AD, and urticaria are relatively common skin diseases; however, they are not well known as adverse effects of TNF-α inhibitors. Although immunological studies were not performed, the clinical courses suggested that these skin disorders might have developed as a result of an immune four-way imbalance in T helper 1 (Th1), Th2, Th17, and regulatory T cells by the administration of TNF-α inhibitors. [ABSTRACT FROM AUTHOR]

Background: Data on the impact of biologics and immunomodulators on coronavirus disease 2019 (COVID-19)-related outcomes remain scarce.Objective: We sought to determine whether patients taking tumor necrosis factor inhibitors (TNFis) or methotrexate are at increased risk of COVID-19-related outcomes.Methods: In this large comparative cohort study, real-time searches and analyses were performed on adult patients who were diagnosed with COVID-19 and were treated with TNFis or methotrexate compared with those who were not treated. The likelihood of hospitalization and mortality were compared between groups with and without propensity score matching for confounding factors.Results: More than 53 million (53,511,836) unique patient records were analyzed, of which 32,076 (0.06%) had a COVID-19-related diagnosis documented starting after January 20, 2020. Two hundred fourteen patients with COVID-19 were identified with recent TNFi or methotrexate exposure compared with 31,862 patients with COVID-19 without TNFi or methotrexate exposure. After propensity matching, the likelihood of hospitalization and mortality were not significantly different between the treatment and nontreatment groups (risk ratio = 0.91 [95% confidence interval, 0.68-1.22], P = .5260 and risk ratio = 0.87 [95% confidence interval, 0.42-1.78], P = .6958, respectively).Limitations: All TNFis may not behave similarly.Conclusion: Our study suggests that patients with recent TNFi or methotrexate exposure do not have increased hospitalization or mortality compared with patients with COVID-19 without recent TNFi or methotrexate exposure. [ABSTRACT FROM AUTHOR]

Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development. Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression. Results: Ten compounds and 128 target genes were screened from SC , of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression. Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Lei, Yao, Zhan, Zhang and Zhou.)

Background: Risk factors for sepsis have not been assessed in patients receiving tumor necrosis factor-alpha inhibitors (TNFi) for immune-mediated inflammatory diseases (IMIDs) who are vulnerable to serious/hospitalized infections. Methods: Data from 2003–2017 were obtained from Taiwan's National Health Insurance Research Database to identify patients receiving TNFi, including etanercept, adalimumab, and golimumab, for IMIDs including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), psoriatic arthritis (PsA), Crohn's disease (CD), and ulcerative colitis (UC). To investigate risk factors for sepsis, we used the Sepsis-3 definition and calculated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression analysis. Results: There were 17,764 patients (mean age 49.3 ± 14.3 years; females, 57.6%) receiving TNFi for IMIDs, including RA (58.6%), AS (19.1%), PsO (15.1%), PsA (2.5%), CD (3.0%), and UC (1.7%). The overall incidence rate of sepsis was 1088 per 100,000 person-years. After adjustment for potential confounders, recent sepsis within 3 months before TNFi initiation (HR, 2.35; 95% CI, 1.73–3.20), CD (HR, 3.36; 95% CI 2.11–5.34; reference group: AS) and glucocorticoid use (prednisolone-equivalent dose, mg/day HR, 1.05; 95% CI, 1.05–1.06) were associated with the risk of sepsis. Intriguingly, golimumab users appeared to have a lower risk of sepsis compared with etanercept users (HR, 0.56; 95% CI, 0.38–0.83). In addition, socioeconomic status, including urbanization level and insured amount, was associated with sepsis in a dose-response manner. Conclusions: Recent sepsis, CD, concomitant glucocorticoid use, and low socioeconomic status, which were associated with an increased risk of sepsis, are crucial for individualized risk management plans. [ABSTRACT FROM AUTHOR]

Objective: to describe a case of the total development of alopecia in a female patient with psoriatic arthritis during treatment with a tumor necrosis factor-αlpha (TNF-α) inhibitor. Materials and methods. Patient I., aged 36 years has been followed up at the Kazan’ Center of Rheumatic Diseases and Osteoporosis since 1998. At approximately the same time, the patient noted the appearance of skin eruptions behind the ears, on the skin of the scalp. She was examined by a dermatologist who diagnosed psoriasis. In 2005, she was admitted to Kazan’ Rheumatology Center, City Clinical Hospital Seven, for the development of obvious synovitis of the knee joint and for the inefficiency of therapy with nonsteroidal anti-inflammatory drugs and diagnosed with psoriatic arthritis. During the prescribed therapy with methotrexate 10 mg/week, evident menstrual irregularities were observed in the patient who stopped using the drug herself. The second pregnancy occurred in 2008. Articular syndrome progression and eruptive psoriasis were recorded in the lactation period. After lactation cessation in 2009, she was hospitalized again. Her examination revealed high laboratory activity (erythrocyte sedimentation rate, as high as 40 mm/hr); magnetic resonance imaging of the knee joints showed the signs of bilateral synovitis; lumbar spine radiography exhibited grade II sacroiliitis. Leflunomide 20 mg/day was recommended as a basic drug. In 2012, the patient used leflunomide, her condition worsened; joint pain progressed; new joints were involved into the process, and cutaneous manifestations were aggravated. To verify a diagnosis and to choose therapy, the patient was referred to a consultation at the Moscow Research Institute of Rheumatology. Results. In connection with the high activity of the disease and with no response to the performed therapy, it was recommended to initiate therapy with biologics, such as infliximab, the drug of choice. Seven infliximab injections were well tolerated: the patient reported lower intensity of joint pains and regression of the skin manifestations of psoriasis. In 2013, after the eighth infliximab injection the patient sought medical advice because of complaints about an obvious exacerbation of psoriasis affecting the trunk, upper and lower extremities, and the development of total alopecia within a week. Discontinuation of cytostatics and biologics was recommended; whether ustekinumab therapy should be used was considered. Conclusion. Practical interest in this clinical case is due to the development of a rare (3.3 %) adverse event in the patient with psoriatic arthritis – hair loss (total development of alopecia) during treatment with a TNF-α inhibitor.

Background: To investigate the impact of smoking on disease activity, treatment retention, and response in patients with ankylosing spondylitis (AS) treated with their first tumor necrosis factor-α inhibitor (TNFi)., Methods: AS patients who started their first TNFi treatment for the active axial disease (BASDAI ≥ 4) from TURKBIO Registry were included. Treatment response of smoker (current and ex-smokers) and nonsmoker (never smoker) patients were primarily evaluated as achievement of BASDAI50 or improvement in BASDAI at least 20 mm at 3 months and 6 months compared to baseline., Results: There were 322 patients with AS (60% male, 59% smoker, mean age: 38.3 years). The median follow-up time was 2.8 years (Q1- Q3: 1.3-3.8), and disease duration was 3.5 years (Q1-Q3: 0.7-8.2). Smokers had male predominance (p < 0.001), lower ESR (p = 0.03), higher BASDAI (p = 0.02), BASFI (p = 0.05), HAQ-AS (p = 0.007), and ASDAS-CRP (p = 0.04) compared with nonsmokers at baseline. In the multivariate analysis, male gender [OR 2.7 (95%CI 1.4-5), p = 0.002], and concomitant conventional synthetic disease-modifying antirheumatic drug use [OR 2.4 (95%CI 1.1-5.2), p = 0.03] were associated with better treatment response. There was an association of male gender [HR 2.4 (95%CI 1.6-3.7), p < 0.001], older age (≥30years) [HR 1.8 (95%CI 1.1-2.8), p = 0.01], and response to treatment [HR 1.8 (95%CI 1.2-2.9), p = 0.008] with better treatment retention. No impact of smoking status was found on treatment retention and response in univariate and multivariate analyses., Discussion: This study suggested that smoking was associated with poorer patient-reported outcomes in biologic naïve AS patients initiating their first TNFi treatment, but it had no impact on the TNFi treatment response and retention rate.

Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200mg every 2 weeks (Q2W) groups starting with LD (400mg Weeks 0/2/4; LD group; J-RAPID: n=82, HIKARI: n=116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n=61, HIKARI: n=99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patientyears]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. Case presentation: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. Conclusion: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Aim: To study the effects of the tumor necrosis factor alpha inhibitor adalimumab on rabbit retina after injection into the vitreous body. Methods: Forty-eight rabbits of mixed strain (9-12 months old, weighing ≈ 3.5 kg) were randomized into four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5 mg) into the eyes of two groups, and balanced salt solution into the eyes of the third group. The fourth group acted as controls. Full-field electroretinography (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6 weeks post-injection the rabbits were euthanized and the sectioned retinas were studied. Retinal histology was studied with hematoxylin-eosin staining. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. Results: No significant difference in ffERG amplitudes or implicit times was observed between the four groups at any time point. Histological and immunohistochemical findings were similar in all groups. Conclusions: Injection of adalimumab into the vitreous body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to the rabbit retina. [ABSTRACT FROM AUTHOR]

Objectives. This 24-week, multicenter, double-blind, randomized, placebo-controlled study (NCT00791999) compared efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) vs placebo plus MTX in Japanese rheumatoid arthritis (RA) patients with inadequate response to MTX. Methods. In total, 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100, 200, or 400 mg (induction dose: 200 mg or 400 mg CZP at Weeks 0, 2, and 4) plus MTX or placebo plus MTX every 2 weeks. Primary endpoint was ACR20 response at Week 12. Results. ACR20 response rates were 62.5%, 76.8%, 77.6%, and 28.6% at Week 12, and 61.1%, 73.2%, 71.8%, and 24.7% at Week 24 for CZP 100, 200, and 400 mg, and placebo groups, respectively, with statistical significance between each CZP group and placebo. Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo. Improvements in health-related quality of life (HRQoL) were observed in all three CZP groups vs placebo. Incidence of adverse events was similar between CZP groups. Conclusions. CZP plus MTX resulted in rapid, sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX, with significant inhibition of radiographic progression and improved HRQoL. [ABSTRACT FROM AUTHOR]

Objective. This 24-week, placebo-controlled, double-blind, randomized study (NCT00791921) investigated efficacy and safety of certolizumab pegol (CZP) in Japanese rheumatoid arthritis (RA) patients in whom methotrexate (MTX) cannot be administered. Methods. A total of 230 patients were randomized to subcutaneous CZP 200 mg (induction dosing: 400 mg at Weeks 0, 2 and 4) or placebo every 2 weeks. Results. ACR20 responses with CZP were rapid and significant versus placebo at Week 1, sustained to Week 12 (67.2% vs. 14.9%) and Week 24 (63.8% vs. 11.4%). Week 24-modified Total Sharp Score (mTSS) change from baseline (CFB) was 0.48 (CZP) versus 2.45 (placebo). CZP treatment was associated with higher Week 12 ACR20 responses versus placebo (with non-MTX disease modifying antirheumatic drugs [DMARDs], 74.2% vs. 20.0%; without [monotherapy], 59.3% vs. 8.2%) and inhibition of radiographic progression at Week 24 (mTSS CFB; with non-MTX DMARDs, 0.24 vs. 1.61; monotherapy, 0.68 vs. 3.65). Incidences of serious adverse events were 11.2% (CZP) and 2.6% (placebo); one CZP patient died of dissecting aortic aneurysm. Conclusion. CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX cannot be administered resulted in rapid, sustained reductions in RA signs and symptoms. Notably, CZP monotherapy showed significant inhibition of radiographic progression. [ABSTRACT FROM AUTHOR]

Refractory recurrent aphthous stomatitis (RRAS) manifests as severe ulcerative lesions of the oral mucosa with poor healing and a poor response to conventional therapy, with or without systemic diseases. Its treatment remains a clinical challenge owing to the lack of effective therapies. Recently, biologics have emerged as promising targeted therapies for RRAS. The biologics targeting specific inflammatory pathways involved in the pathogenesis of RRAS, including tumor necrosis factor-alpha inhibitors and interleukin inhibitors, offer a more precise and promising therapeutic approach for RRAS. These targeted therapies have been shown to promote healing and decrease recurrence frequency in, and improve the quality of life of patients with RRAS. Herein, the types and mechanisms of biologics currently used to treat RRAS have been reviewed; furthermore, the dose, duration, therapeutic efficacy, and adverse effects of RRAS with or without certain associated systemic diseases, and the current problems and future directions have been discussed., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 65-year-old man was admitted to our hospital with a temperature of 39.3 °C, cough, sputum, and pharyngeal discomfort that had persisted for 3 days. He had been treated with methotrexate and adalimumab (a tumor necrosis factor-alpha [TNF-α] inhibitor) for rheumatoid arthritis for 2 years, and he had also been treated with S-1 (tegafur, gimeracil, and oteracil potassium) for pancreatic metastasis of gastric cancer for 2 months. Regardless of the underlying pathologies, his general condition was good and he had worked as an electrician until 2 days before admission. However, his appetite had suddenly decreased from the day before admission, and high fever and hypoxia were also evident upon admission. A chest X-ray and computed tomography scan revealed left pleural effusion and consolidation in both lungs. The pneumonia severity index score was 165 and the risk class was V. Accordingly, we started to treat the pneumonia with a combination of levofloxacin and meropenem. Thereafter, we received positive urinary antigen test findings for Legionella pneumophila. After hospitalization, hypoxia was progressed and hypotension was emerged. Despite the application of appropriate antibiotics, vasopressors, and oxygenation, the patient died 8 h after admission. Even after his death, blood cultures were continued to consider the possibility of bacterial co-infection. Although no bacteria were detected from blood cultures, Gimenez staining revealed pink bacteria in blood culture fluids. Subsequent blood fluid culture in selective medium revealed L. pneumophila serogroup 1. Recently, TNF-α inhibitors have been described as a risk factor for Legionnaires' disease. In consideration of the increased frequency of TNF-α inhibitors, we may need to recognize anew that L. pneumophila might be a pathogen of severe community-acquired pneumonia. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor inhibitory agents are currently considered to be contraindicated in psoriatic patients with hepatitis B. Objective: We aim to provide guidance to dermatologists on the use of tumor necrosis factor inhibitor therapy in these patients. Methods: The current literature was reviewed regarding the use of tumor necrosis factor-alpha inhibitory agents (etanercept, adalimumab, and infliximab) in psoriatic patients with particular reference to hepatitis B infection. Results: Tumor necrosis factor-alpha inhibitor therapy may result in reactivated hepatitis B in hepatitis B surface antigen-positive patients with psoriasis. This also occurs, although less frequently in patients with an isolated positive hepatitis B core antibody. Thus, all psoriasis patients should be screened for hepatitis B surface antigen plus hepatitis B core antibody prior to the initiation of tumor necrosis factor-alpha inhibitor therapy. Infliximab has been associated with more reactivation cases than the other 2 agents and fatalities have been reported with this agent. Evidence is presented that the risk of reactivation can be greatly minimized or eliminated by early or pre-emptive antiviral therapy. Limitations: The data is largely based on small case series that are retrospective in nature. Conclusions: Hepatitis B screening is essential prior to the initiation of tumor necrosis factor-alpha inhibitor therapy. Psoriatic patients found to be hepatitis B surface antigen or hepatitis B core antibody-positive should be referred to an appropriate specialist for evaluation and therapy. This would allow for the safe use of tumor necrosis factor-alpha inhibitors in psoriatic patients despite recently published guidelines to the contrary. [ABSTRACT FROM AUTHOR]

Biosimilars can reduce healthcare costs and expand patient access to biologic therapies. Currently, eight adalimumab biosimilars have received regulatory approval from the EMA and/or the US FDA. Following recent EMA approval of the first high-concentration adalimumab biosimilar, CT-P17, this review provides a contemporary update on adalimumab biosimilars currently licensed in Europe and the USA. The totality of evidence from each clinical development program is summarized, and characteristics of each formulation and/or device that potentially affect the convenience of treatment for patients are discussed. Future perspectives are considered, including the potential impact of the FDA's first interchangeability designation for an adalimumab biosimilar, ahead of their entry into the US marketplace in 2023.