Mechanisms underlying the therapeutic effects of Semen cuscutae in treating recurrent spontaneous abortion based on network pharmacology and molecular docking.

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.

The safety and efficacy of tumor necrosis factor-alpha inhibitor on pregnancy outcomes in patients with unexplained recurrent miscarriage.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Paradoxical Psoriasis.

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.

Dysbiosis in Inflammatory Bowel Disease and Spondyloarthritis: Still a Long Way to Go?

The association between Inflammatory Bowel Disease (IBD) and Spondyloarthritis (SpA) has been known for years, as has the concept that IBD is associated with an altered intestinal bacterial composition, a condition known as "dysbiosis". Recently, a state of intestinal dysbiosis has also been found in SpA. Dysbiosis in the field of IBD has been well characterized so far, as well as in SpA. The aim of this review is to summarize what is known to date and to emphasize the similarities between the microbiota conditions in these two diseases: particularly, an altered distribution in the gut of Enterobacteriaceae, Streptococcus, Haemophilus, Clostridium, Akkermansia, Ruminococcus, Faecalibacterium Prausnitzii, Bacteroides Vulgatus, Dialister Invisus, and Bifidubacterium Adolescentis is common to both IBD and SpA. At the same time, little is known about intestinal dysbiosis in IBD-related SpA. Only a single recent study has found an increase in Escherichia and Shigella abundances and a decrease in Firmicutes, Ruminococcaceae, and Faecalibacterium abundances in an IBD-related SpA group. Based on what has been discovered so far about the altered distribution of bacteria that unite both pathologies, it is appropriate to carry out further studies aiming to improve the understanding of IBD-related SpA for the purpose of developing new therapeutic strategies.

A teenage girl with altered mental status and paraparesis.

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.

Safety risks of interstitial lung disease upon real-world usage of Janus kinase inhibitors and biologics for patients with autoimmune diseases: epidemiological study using nationwide electronic medical record database in Japan.

Although Janus kinase inhibitor (JAKi) therapy is used for patients with autoimmune diseases (AD), one safety concern, interstitial lung disease (ILD), is life-threatening. We evaluated actual usage of JAKi and safety upon JAKi treatment, in an epidemiological retrospective cohort study utilizing the electronic medical record database in Japan. Among 391,565 AD patients, we analyzed data of new-users receiving JAKi or tumor necrosis factor alpha inhibitor (TNFi)/biologics during the period July 2013-May 2022. ILD (ICD10: J70.2, J70.3, J70.4 and J84) criteria were defined: new-ILD (1) and new-ILD (2) which differed in the latter's prompter therapeutics cessation upon ILD development. We analyzed ILD occurrence and death, ILD cumulative incidence by the Kaplan-Meier method, and hazard ratio (HR) by the Cox model, for 957 JAKi and 3931 TNFi users. JAKi use has become widespread amidst additional drug-development. Among JAKi users, two-year new-ILD (2) incidence, at 1.4%, was higher than for TNFi users (risk ratio: new-ILD (2) 1.75, death 2.31). Cumulative incidence (2.9% in 20.48 days) was also significantly higher (log-rank test p = .013, HR 2.23 (95% CI 1.16-4.27)); risk factors estimated by HR included JAKi (2.14), rheumatoid arthritis (4.94), diabetes mellitus (2.67) and cerebrovascular disease (2.86). ILD screening is essential.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

The impact of smoking on response to tumor necrosis factor-α inhibitor treatment in patients with ankylosing spondylitis.

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.

Effect of extended dosing interval of anti-TNF-alpha NANOBODY® compound ozoralizumab in patients with low disease activity rheumatoid arthritis.

OBJECTIVE: To evaluate the effect of extended dosing interval on the efficacy and safety of ozoralizumab in patients with rheumatoid arthritis (RA). METHODS: In a long-term extension study (HOSHIZORA trial) for patients who had completed a phase II/III study with methotrexate (MTX) or a phase III study without MTX, the dosing interval of ozoralizumab was allowed to extend from every 4 weeks (Q4W) to every 8 weeks (Q8W), at the physician's discretion, for patients who had maintained DAS28-ESR <3.2 at the last two time points. The continuation rate, efficacy and safety were examined in patients who had completed 24 weeks after the change in the dosing interval by the data cut-off point. RESULTS: Of the 32 patients who maintained DAS28-ESR <3.2 and changed the interval from Q4W to Q8W, 28 (87.5%) remained on Q8W for 24 weeks. At week 24, the percentages of patients who remained on Q8W and achieved DAS28-ESR <2.6 and <3.2 were 71.9% and 84.4%, respectively. No safety concerns were observed for 24 weeks in the Q8W group. CONCLUSIONS: In patients with RA and maintained DAS28-ESR <3.2 with ozoralizumab, efficacy was sustained and well tolerated after the dosing interval was extended from Q4W to Q8W.

Successful treatment of necrobiosis lipoidica and associated retinal vasculitis with tumor necrosis factor (TNF)-alpha inhibitor.

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.

Have we got the optimal treatment for refractory Kawasaki disease in very young infants? A case report and literature review.

A small group of patients with Kawasaki disease (KD) demonstrates resistance to standard therapy, putting them at high risk for an unfavorable prognosis, especially regarding coronary artery aneurysms. Although adding corticosteroids to first-line i.v. immunoglobulins (IVIGs) is considered beneficial, and despite timely treatment initiation, very young infants, in particular, can present an unfavorable clinical course. We report on a 3-month-old boy with a clinically severe KD phenotype involving the early development of giant coronary artery aneurysms. Because of his poor response to the first course of IVIG and prednisolone, we administered infliximab. His clinical condition improved after that, and his temperature dropped. Inflammatory markers however did not recover completely, and he remained subfebrile. In addition, as the coronary artery dimensions deteriorated, a second IVIG course was administered and prednisolone continued at the initial dosage. Although fever and routine inflammatory parameters normalized, close follow-up investigations revealed both still increasing coronary artery dimensions and renewed rise in inflammatory parameters, necessitating two more infliximab administrations in addition to continuous prednisolone. Because of the coronary artery dimensions (left anterior descending artery, 4.9 mm, Z-score 11.1; right coronary artery 5.8 mm, Z-score 15.5), dual platelet inhibitory therapy with ASA and later clopidogrel combined with low-molecular heparin was indicated. Four weeks after his initial KD diagnosis, we detected no renewed increase in inflammatory markers; at that time, we observed a slight reduction in coronary dimensions. In summary, despite timely guideline-fulfilling therapy, the prolonged clinical course of this very young infant with KD entailing the development of giant coronary artery aneurysms makes us question whether this age group may benefit from early, even more intense therapy.

Recent Advancements in Epidural Etanercept for Pain Management in Radiculopathy: A Literature Review.

The most common etiology of low back and neck pain is associated with spinal cord pathologies. Regardless of origin, low back and neck pain are some of the most common causes of disability worldwide. Mechanical compression due to spinal cord diseases, such as degenerative disc disorders, can lead to radiculopathy, which manifests as numbness or tingling and can progress to loss of muscle function. Conservative management, such as physical therapy, has not been proven effective in treating radiculopathy, and surgical treatments have more risks than benefits for most patients. Epidural disease-modifying medications, such as Etanercept, have been recently explored due to their minimal invasiveness and direct effects on inhibiting tumor necrosis factor-α (TNF-α). Therefore, this literature review aims to evaluate epidural Etanercept's effect on radiculopathy caused by degenerative disc diseases. Epidural Etanercept has been shown to improve radiculopathy in patients with lumbar disc degeneration, spinal stenosis, and sciatica. Further research is needed to compare the effectiveness of Etanercept with commonly used treatments such as steroids and analgesia.

Efficacy and pharmacokinetics of ozoralizumab, an anti-TNFα NANOBODY® compound, in patients with rheumatoid arthritis: 52-week results from the OHZORA and NATSUZORA trials.

INTRODUCTION: Ozoralizumab (OZR), a tumor necrosis factor alpha (TNFα) inhibitor, is a NANOBODY® compound that binds to TNFα and human serum albumin. The main objective of this study was to analyze the pharmacokinetics (PK) of the drug and its correlation with clinical efficacy in patients with rheumatoid arthritis (RA). METHODS: Efficacy data were analyzed from the OHZORA trial, in which OZR 30 or 80 mg was administered to Japanese patients with RA at 4-week intervals for 52 weeks in combination with methotrexate (MTX; n = 381), and the NATSUZORA trial, in which OZR 30 or 80 mg was administered without concomitant MTX (n = 140). Effects of patient baseline characteristics and anti-drug antibodies (ADAs) on the PK and efficacy of OZR were investigated, and a post hoc analysis of PK effects on drug efficacy was performed. RESULTS: The maximum plasma concentration (Cmax) was reached in 6 days in both the 30 and 80 mg groups, with an elimination half-life of 18 days. The Cmax and area under the plasma concentration-time curve increased in a dose-dependent manner, and the trough concentration reached steady state by week 16. The exposure of OZR correlated negatively with patient body weight and was not affected by other patient baseline characteristics. Effects of ADAs on the exposure and efficacy of OZR were limited in both trials. However, antibodies that neutralize the binding to TNFα had some effect on the exposure and efficacy of OZR in the NATSUZORA trial. The receiver operating characteristic analysis of the effect of trough concentration on the American College of Rheumatology 20% and 50% improvement rates was retrospectively performed, and a cutoff trough concentration of approximately 1 µg/mL at week 16 was obtained in both trials. The efficacy indicators in the subgroup with trough concentration ≥ 1 µg/mL were higher than those in the < 1 µg/mL subgroup at week 16, while no clear cutoff was obtained at week 52 in both trials. CONCLUSIONS: OZR showed a long half-life and favorable PK properties. A post hoc analysis suggested sustained efficacy independent of trough concentration by subcutaneous administration of OZR 30 mg at 4-week intervals for 52 weeks. TRIAL REGISTRATION: JapicCTI, OHZORA trial: JapicCTI-184029, registration date July 9, 2018; NATSUZORA trial: JapicCTI-184031, registration date July 9, 2018.

Associations of Tinnitus Incidence with Use of Tumor Necrosis Factor-Alpha Inhibitors among Patients with Autoimmune Conditions.

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.

Chronic Inflammatory Demyelinating Polyneuropathy After Therapy With Infliximab Biosimilar.

Tumor necrosis factor-α inhibitors are monoclonal antibodies that are commonly used in the treatment of inflammatory bowel disease. A rare side effect of these biological agents is chronic inflammatory demyelinating polyneuropathy, which is a debilitating disease characterized by weakness, sensory dysfunction, and diminished or absent reflexes. We present the first reported case of chronic inflammatory demyelinating polyneuropathy after treatment with the tumor necrosis factor-α inhibitor biosimilar, infliximab-dyyp (Inflectra).

Increased protein phosphatase 5 expression in inflammation-induced left ventricular dysfunction in rats.

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 (sGCß2) 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 sGCß2 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.

Clinical course of Covid-19 in a cohort of patients with Behçet disease.

Objective: The implications of Covid-19 in patients with Behçet's disease (BD) are unknown. Patients with BD usually take long-term therapy with therapeutic agents that have been tested in Covid-19 patients. We aimed to assess the prevalence of Covid-19 in a cohort of patients with BD and investigate whether those patients with a long-term treatment with colchicine, tumor necrosis factor inhibitors (TNFi) or glucocorticoids are at reduced or increased prevalence of Covid-19 related clinical outcomes. Methods: A retrospective study was conducted among 244 patients with BD (86.1% females; mean age 43.95 ± 11.11 years). Each participant completed an online questionnaire regarding demographics, medical conditions, dispensed colchicine, TNFi or oral glucocorticoids, Covid-19 infection, clinical symptoms and recovery. Results: The prevalence of Covid-19 infection was 14.75%. Regarding dose of colchicine, the presence of ageusia was lower in patients taking 0.5 mg/day of colchicine compared to those taking 1.5 mg/day (p = 0.021). The prevalence of dyspnea was significantly higher in patients taking TNFi compared with those without therapy (p = 0.032). With regards to oral glucocorticoids, no significant differences were found. Conclusions: The prevalence of Covid-19 among patients with BD seems to be higher than that among the general population in Spain. Continuous TNFi therapy might increase the prevalence of worse clinical outcomes such as dyspnea; oral glucocorticoids and colchicine apparently provided no protection against the Covid-19 related clinical outcomes of patients with BD.

Objetivo: Se desconocen las implicaciones de la Covid-19 en pacientes con enfermedad de Behçet (EB). Los pacientes con EB generalmente tienen tratamiento de larga duración con agentes terapéuticos que se han probado en pacientes con Covid-19. Nuestro objetivo fue evaluar la prevalencia de la Covid-19 en una cohorte de pacientes con EB e investigar si los pacientes con un tratamiento de larga duración con colchicina, inhibidores del factor de necrosis tumoral (TNFi) o glucocorticoides tienen una prevalencia reducida o aumentada en los resultados clínicos de la Covid-19. Métodos: Se realizó un estudio retrospectivo en 244 pacientes con EB (86,1% mujeres; edad media, 43,95 ± 11,11 años). Cada participante completó un cuestionario en línea sobre datos demográficos, afecciones médicas, tratamiento con colchicina, TNFi o glucocorticoides orales, infección por Covid-19, síntomas clínicos y recuperación. Resultados: La prevalencia de la infección por Covid-19 fue del 14,75%. En cuanto a la dosis de colchicina, la presencia de ageusia fue menor en los pacientes que tomaban 0,5 mg/día de colchicina en comparación con los que tomaban 1,5 mg/día (p = 0,021). La prevalencia de disnea fue significativamente mayor en los pacientes que tomaban TNFi en comparación con aquellos sin terapia (p = 0,032). Con respecto a los glucocorticoides orales, no se encontraron diferencias significativas. Conclusiones: La prevalencia de Covid-19 en pacientes con EB parece ser superior a la de la población general en España. La terapia continua con TNFi podría aumentar la prevalencia de peores resultados clínicos como la disnea; los glucocorticoides orales y la colchicina aparentemente no proporcionan protección contra los resultados clínicos relacionados con la Covid-19 en pacientes con EB.

Clinical course of Covid-19 in a cohort of patients with Behçet disease

Objective: The implications of Covid-19 in patients with Behçet's disease (BD) are unknown. Patients with BD usually take long-term therapy with therapeutic agents that have been tested in Covid-19 patients. We aimed to assess the prevalence of Covid-19 in a cohort of patients with BD and investigate whether those patients with a long-term treatment with colchicine, tumor necrosis factor inhibitors (TNFi) or glucocorticoids are at reduced or increased prevalence of Covid-19 related clinical outcomes.MethodsA retrospective study was conducted among 244 patients with BD (86.1% females; mean age 43.95±11.11 years). Each participant completed an online questionnaire regarding demographics, medical conditions, dispensed colchicine, TNFi or oral glucocorticoids, Covid-19 infection, clinical symptoms and recovery.ResultsThe prevalence of Covid-19 infection was 14.75%. Regarding dose of colchicine, the presence of ageusia was lower in patients taking 0.5mg/day of colchicine compared to those taking 1.5mg/day (p=0.021). The prevalence of dyspnea was significantly higher in patients taking TNFi compared with those without therapy (p=0.032). With regards to oral glucocorticoids, no significant differences were found.ConclusionsThe prevalence of Covid-19 among patients with BD seems to be higher than that among the general population in Spain. Continuous TNFi therapy might increase the prevalence of worse clinical outcomes such as dyspnea; oral glucocorticoids and colchicine apparently provided no protection against the Covid-19 related clinical outcomes of patients with BD. (AU)

Objetivo: Se desconocen las implicaciones de la Covid-19 en pacientes con enfermedad de Behçet (EB). Los pacientes con EB generalmente tienen tratamiento de larga duración con agentes terapéuticos que se han probado en pacientes con Covid-19. Nuestro objetivo fue evaluar la prevalencia de la Covid-19 en una cohorte de pacientes con EB e investigar si los pacientes con un tratamiento de larga duración con colchicina, inhibidores del factor de necrosis tumoral (TNFi) o glucocorticoides tienen una prevalencia reducida o aumentada en los resultados clínicos de la Covid-19.MétodosSe realizó un estudio retrospectivo en 244 pacientes con EB (86,1% mujeres; edad media, 43,95±11,11 años). Cada participante completó un cuestionario en línea sobre datos demográficos, afecciones médicas, tratamiento con colchicina, TNFi o glucocorticoides orales, infección por Covid-19, síntomas clínicos y recuperación.ResultadosLa prevalencia de la infección por Covid-19 fue del 14,75%. En cuanto a la dosis de colchicina, la presencia de ageusia fue menor en los pacientes que tomaban 0,5mg/día de colchicina en comparación con los que tomaban 1,5mg/día (p=0,021). La prevalencia de disnea fue significativamente mayor en los pacientes que tomaban TNFi en comparación con aquellos sin terapia (p=0,032). Con respecto a los glucocorticoides orales, no se encontraron diferencias significativas.ConclusionesLa prevalencia de Covid-19 en pacientes con EB parece ser superior a la de la población general en España. La terapia continua con TNFi podría aumentar la prevalencia de peores resultados clínicos como la disnea; los glucocorticoides orales y la colchicina aparentemente no proporcionan protección contra los resultados clínicos relacionados con la Covid-19 en pacientes con EB. (AU)