Tumor Necrosis Factor Alpha Inhibitors Research Articles

Remitting seronegative symmetrical synovitis with pitting edema syndrome: case report of an atypical presentation of a rare syndrome and literature review

BackgroundRemitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome. The following case shows an atypical course of the disease with successful treatment. In addition, the accompanied review highlights current findings in the pathogenesis and treatment. Clinicians should be aware of the differential diagnosis of RS3PE syndrome.Case presentationA 67-year-old female patient with recurrent, asymmetric, and painful swelling of both hands with pitting edema, predominantly affecting the dorsal right hand, presented at our in-patient clinic. Over the years of her disease, first diagnosed as rheumatoid arthritis and then psoriatic arthritis, prednisolone treatment had the most favorable effects over various disease-modifying antirheumatic drugs.Subsequent diagnostic evaluation confirmed RS3PE syndrome, a rare inflammatory disorder primarily affecting the elderly population. Manifesting as symmetrical joint inflammation of small joints with pitting edema, RS3PE syndrome typically onsets suddenly and may be accompanied by systemic symptoms like fever, fatigue, and weight loss. Although the precise etiology remains enigmatic, both the innate and the adaptive immune system seem to play a pathogenic role. Treatment is conventionally based on prednisolone, which effectively mitigates symptoms.Ultimately, RS3PE was diagnosed in the context of psoriatic arthritis without dermatological or nail involvement. Given the unusual presentation marked by female gender, asymmetry, and prolonged and extensive disease with various prior treatments and in the context of psoriatic arthritis, a tumor necrosis factor alpha inhibitor was initiated in addition to low-dose prednisolone resulting in clinical remission for the first time.ConclusionsIn conclusion, the aforementioned atypical manifestation highlights the significance of including RS3PE syndrome as a potential differential diagnosis, particularly in instances where specific diagnostic criteria for rheumatoid arthritis, polymyalgia rheumatica, or psoriatic arthritis are absent. RS3PE responds well to the administration of prednisolone. In refractory cases, a therapeutic trial with tumor necrosis factor alpha inhibitors can be conducted.

Gender disparities in Behçet's syndrome: identifying distinct phenotypes through cluster analysis.

Behçet's syndrome (BS) is a complex, multi-systemic disorder with a global occurrence, notably concentrated along the Silk Road. This study aimed to investigate gender-specific expressions and clinical phenotypes in BS patients within the Eastern Black Sea Region of Turkey. A total of 290 BS patients were retrospectively analyzed between January 2013 and December 2023. Demographic characteristics, clinical manifestations, medical treatment, and pathergy test results were obtained from a review of medical records. The mean age was 45.79 ± 13.05, with a male-to-female ratio of 48.6:51.4. Male patients had higher papulopustular lesions (p < 0.001) and ocular involvement (p = 0.036), while females showed more frequent genital ulcers (p = 0.032). Medication usage showed gender-based variations, notably higher corticosteroid, azathioprine, and tumor necrosis factor-alpha inhibitor (TNFi) use in males (p < 0.001). Cluster analysis revealed five distinct clusters, each with unique features and gender predominance. Cardiovascular type, ocular type, and skin type predominantly featured male patients, while joint involvement type and neurologic and mucosal involvement type were more prevalent among female patients with BS. This research contributes valuable insights into the gender-related clinical variations of BS within a specific geographic region, fostering a more comprehensive understanding of this challenging syndrome. The identification of distinct clinical phenotypes facilitates the development of tailored treatment strategies, potentially leading to improved outcomes for patients with BS.

Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR2.84, p = 0.02). In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.

Certolizumab pegol effectiveness, survival and safety in patients with psoriasis: A multicenter retrospective analysis in daily clinical practice by the Spanish Psoriasis Group.

Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions. This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting. A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn. Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice.

Rituximab for rheumatoid arthritis-related interstitial lung disease: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed at summarizing the evidence of efficacy and safety of rituximab in rheumatoid arthritis-related interstitial lung disease (RA-ILD). PubMed and Embase databases were searched until June 22, 2022, to identify studies on RA-ILD treated with rituximab, confined to predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies to assess the overall stabilization or improvement in ILD, changes in percent-predicted (%-predicted) forced vital capacity (FVC), and %-predicted diffusion capacity of lungs for carbon monoxide (DLCO) following rituximab therapy. A total of 15 studies (4 prospective and 11 retrospective studies) were included, with a total of 314 patients. There were 105 (60.7%) females out of 173 subjects for whom sex details were available from seven studies. The overall pooled proportion of patients with stabilization or improvement in ILD was 0.88 [95% confidence interval (CI): 0.76-0.96, p=0.02]. Rituximab improved FVC from baseline by 7.50% (95% CI: 1.35-13.65; p=0.02, fixed effect). Similarly, rituximab improved DLCO by 6.39% (95% CI: 1.366-14.43; p=0.12, random-effect). Two retrospective studies reported reduced mortality with rituximab therapy compared to tumor necrosis factor-alpha inhibitors. Treatment with rituximab in RA-ILD was associated with a significant improvement in %-predicted FVC, as well as stabilization or improvement in ILD after one year of treatment.

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

ObjectivesAlthough 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. MethodsThis 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. ResultsIn 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. ConclusionsTNFi, 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.

Knowledge framework of intravenous immunoglobulin resistance in the field of Kawasakidisease: A bibliometric analysis (1997-2023).

Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research. Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots. Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and theJournal of Pediatricshad the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers. Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor-alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS-C). "Treatment," "risk factor," and "prediction" were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high-throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.

Low incidence of invasive fungal infection and risk factors in a large observational cohort of patients initiating tumor necrosis factor-alpha inhibitors for dermatologic conditions

Low incidence of invasive fungal infection and risk factors in a large observational cohort of patients initiating tumor necrosis factor-alpha inhibitors for dermatologic conditions

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy

BackgroundWe aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi).MethodsUsing the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA.ResultsThis study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (\U0001d6fd = 0.343, p = 0.011), whereas ASDAS was not (\U0001d6fd = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200–2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678–1.455), after adjusting for other baseline characteristics.ConclusionsThe changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

Should Histoplasmosis be Screened for Before Initiation of Tumour Necrosis Factor Alpha Inhibitors?

Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.

Evaluation of inflammatory biomarkers and the ratio of hemoglobin-red cell distribution width in patients with rheumatoid arthritis treated with tumor necrosis factor-alpha inhibitors.

The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors.

In-vitro and In-vivo Studies of Anti-inflammatory Potential of Compounds Derived from Piper mullesua

The identification and development of new anti-inflammatory drugs continue to benefit greatly from the use of natural substances and their synthetic counterparts. Studies have been conducted on a compounds obtained from the Piper mullesua plant. The current work aims to use in-vitro and in-vivo experiments to investigate these substances’ anti-inflammatory properties. Our investigation’s findings showed that various substances had varying percentages of cell viability on RAW 264.7 cells. These substances were also tested for suppression of nitric oxide. Novel approaches to the creation of pharmaceuticals have demonstrated the potential of natural product derivatives. This study set out to investigate PM208-209’s potential anti-inflammatory properties. The impact of PM208-209 on inhibiting tumor necrosis factor-alpha (TNF-α) and IL-6 in LPS-induced RAW 264.7 cells was examined using enzyme-linked immunosorbent assay (ELISA). Additionally, PM208-209 demonstrated anti-inflammatory effects in mice, as evidenced by the suppression of vascular permeability and migration of leukocytes. The information gathered suggested that PM208-209 should be investigated further in terms of pharmacological research and could be regarded as a possible therapeutic anti-inflammatory option

Full Guidelines—From the Medical Board of the National Psoriasis Foundation: Perioperative management of systemic immunomodulatory agents in patients with psoriasis and psoriatic arthritis

BackgroundSystemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection and complication. ObjectiveTo evaluate the risk of surgical site infection and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alpha inhibitors, interleukin [IL]-12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte–associated antigen-4 co-stimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine, and methotrexate) undergoing surgery. MethodsWe performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery. ResultsWe examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. ConclusionFor low-risk procedures, TNF-alpha inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, methotrexate, cyclosporine, and apremilast can safely be continued. For intermediate- and high-risk surgery, methotrexate, cyclosporine, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib.

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry.

An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries.

To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared. 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total. Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19. Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.

Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients.

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change -0.97, 95%CI -4.30; 2.37, [p = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [p = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI -1.84; 6.85 [p = 0.031]) and non-responders (2.48, 95%CI -1.46; 6.41 [p = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients.

Effects of tumor necrosis factor-alpha inhibitors on lipid profiles in patients with psoriasis: a systematic review and meta-analysis.

There is no consensus on the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitors on lipid profiles in patients with psoriasis. This study aimed to investigate the effects of TNF-alpha inhibitors on lipid profiles (triglycerides, total cholesterol, low-density lipoprotein, or high-density lipoprotein) in patients with psoriasis. We searched PubMed, Embase, and Cochrane Library databases for articles published before October 17, 2023. Four TNF-alpha inhibitors (infliximab, etanercept, adalimumab, and certolizumab) were included in our study. (PROSPERO ID: CRD42023469703). A total of twenty trials were included. Overall results revealed that TNF-alpha inhibitors elevated high-density lipoprotein levels in patients with psoriasis (WMD = 2.31; 95% CI: 0.96, 3.67; P = 0.001), which was supported by the results of sensitivity analyses excluding the effect of lipid-lowering drugs. Subgroup analyses indicated that high-density lipoprotein levels were significantly increased in the less than or equal to 3 months group (WMD = 2.88; 95% CI: 1.37, 4.4; P < 0.001), the etanercept group (WMD = 3.4; 95% CI = 1.71, 5.09, P < 0.001), and the psoriasis group (WMD = 2.52; 95% CI = 0.57, 4.48, P = 0.011). Triglyceride levels were significantly increased in the 3 to 6-month group (WMD = 4.98; 95% CI = 1.97, 7.99, P = 0.001) and significantly decreased in the 6-month and older group (WMD = -19.84; 95% CI = -23.97, -15.7, P < 0.001). Additionally, Triglyceride levels were significantly increased in the psoriasis group (WMD = 5.22; 95% CI = 2.23, 8.21, P = 0.001). Our results revealed that TNF-alpha inhibitors might temporarily increase high-density lipoprotein levels in patients with psoriasis. However, changes in triglycerides were not consistent among the different durations of treatment, with significant increases after 3 to 6 months of treatment. Future prospective trials with long-term follow-up contribute to confirming and extending our findings. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469703.

Synergistic Interaction between Topical Application of Allicin and Quercetin Enhances Diabetic Wound Healing Via Inflammatory in Wistar Rats

Prolonged and excessive inflammatory processes at the wound site result in delayed healing of diabetic wounds. Allicin and quercetin have significantly inhibited tumor necrosis factor alpha (TNF-α) and increased levels of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) in rats. However, there is no known investigation on the combination of both compounds on TNF-α, TGF-β, and VEGF as a topical healing agent via inflammatory mechanisms. This study aims to determine the synergistic interaction between topical application of allicin and quercetin in enhancing diabetic wound healing via inflammatory in Wistar rats. A total of 45 male Wistar rats weighing 180-250 g were induced diabetes by a single intraperitoneal injection of streptozotocin (45 mg/kg bw). Diabetic rats underwent wound creation under anaesthesia and a square-shaped open excision wound was made with a full-thickness measurement of 1 cm × 1 cm on the right side of the rat's back. Rats were randomly allocated into group namely, vehicle control, allicin, quercetin, and a combination of allicin and quercetin which is applied topically once a day at a dose of 10 mg/mL for 7 days. Our finding showed that once daily topical application of allicin and quercetin, both independently and synergistically, increased levels of TGF-β and VEGF, as well as decreased levels of TNF-α of the rat diabetic wound model compared with the vehicle control group over 7th day. The synergistic effects of allicin and quercetin significantly enhanced diabetic wound healing via inflammation in rats, by suppressing inflammatory cytokines and stimulating growth factors hence offering a new window of an experimental study.

Certolizumab pegol in severe rheumatoid arthritis: Real-world evidence in an Argentine cohort: Achievement of targets (T2T) at 3 months and predictive factors.

Introduction: Certolizumab pegol (CTZ) is a tumor necrosis factor-alpha (TNF-α) inhibitor biological agent that has demonstrated efficacy in controlling rheumatoid arthritis (RA). Identifying predictive factors for treatment success and assessing its effectiveness in a real-world clinical setting are crucial for decision-making. Objective: To evaluate the response to CTZ in patients with RA in a real-world cohort, measuring the reduction in DAS 28, HAQ, frequency of remission, and low disease activity (LDA) at three months, identifying predictive factors, and evaluating the reduction in the use of corticosteroids. Methods: A prospective real-world observational study included patients over 18 years of age with RA (ACR/EULAR 2010 criteria) who initiated CTZ and were followed for three months. Demographic, clinical, comorbidity, treatment, and disease activity data were recorded. Results: Out of 2092 RA patients treated with CTZ between 2016 and 2021, 90% had a poor prognosis, and 60% had high disease activity. Among 1673 patients followed for three months, a reduction in DAS 28 (-1.9) and HAQ (-0.63) was observed. At three months, 10.5% achieved remission, and 40% achieved LDA. Predictive factors for remission included age (OR: 0.97) and DAS 28 (OR: 0.58); for LDA, age (OR: 0.97), DAS 28 (OR: 0.61), first-line CTZ (OR: 1.6), and HAQ (OR: 0.61). Additionally, there was a reduction in the use of glucocorticoids (-3.1 mg prednisone). Conclusions: CTZ is effective in RA, emphasizing patient selection and an early treatment approach. This study supports the efficacy of CTZ.

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.