Tumor Necrosis Factor Alpha Inhibitors Research Articles

Paediatric Uveitis - the uniqueness in clinical presentation and the efficacy of biologics treatment

AimsTo evaluate unique clinical characteristics of paediatric uveitis in our locality and treatment outcomes especially the efficacy of biologics.MethodsThis was a retrospective cohort.Results37 paediatric uveitis cases involving 67 eyes were included. Male-to-female ratio was 1:1.3. Mean age of uveitis onset was 11 ± 3.7 (4–18). 81.1% cases suffered from bilateral uveitis. 75.7% cases were chronic uveitis. Nearly half of the cases (40.5%) presented with anterior uveitis. The predominant diagnosis of uveitis in our cohort was idiopathic. Unlike studies from other populations, the associated systemic conditions in this mostly Chinese cohort were Behçet’s disease (8.1%), tubulointerstitial nephritis and uveitis (8.1%) and HLA-B27 associated uveitis (8.1%). Steroid response was a common phenomenon, observed in 40.5% of cases. The most common complication was posterior synechiae (45.9%), followed by cataract (37.8%), glaucoma (27.0%), band keratopathy (18.9%) and macular oedema (13.5%). 3/37 patients encountered either first attack of uveitis or flare after receiving COVID-19 vaccine. 54.1% of patients required systemic steroid for disease control. The majority required steroid sparing immunotherapy, including Methotrexate (43.2%), Mycophenolate Mofetil (24.3%), Cyclosporine A (8.1%), Azathioprine (5.4%) and Tacrolimus (2.7%). Resistant cases required biologics including tumour necrosis factor alpha inhibitors (Adalimumab 32.4%, Infliximab 2.7%) and interleukin-6 inhibitors (Tocilizumab 2.7%).ConclusionsClinical presentation of the local paediatric uveitis differs from previously described features in Caucasian and other populations. According to our experience as a tertiary eye centre, Behçet’s disease, tubulointerstitial nephritis and uveitis and HLA-B27 associated uveitis were more often encountered than Juvenile Idiopathic Arthritis associated uveitis. Our report evaluated the efficacy of immunomodulatory therapy and biologics in controlling uveitis and reducing ocular complications.

Predicting the course of uveitis against the background of juvenile idiophatic arthritis when using topical therapy regimens. The results of mathematical modeling

BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in children, and uveitis is its most destructive extra-articular manifestation. Despite the existence of Federal clinical guidelines for the management of these patients, their treatment is largely based on the experience of doctors and varies greatly even within the same country. AIM: The aim of the study is to find factors for predicting the course of uveitis and optimizing therapy. MATERIALS AND METHODS: The case histories of 150 children aged 1.5 to 17 years with active uveitis in the structure of juvenile arthritis were analyzed using multifactorial modeling (construction of classification trees). RESULTS: The fact of a significant influence of the time elapsed from the onset of rheumatic disease and uveitis until the start of therapy by genetically engineered medications (tumor necrosis factor alpha inhibitors) in treatment programs has been established. CONCLUSIONS: Thus, the inclusion of this factor into the group of controlling ones makes it possible to achieve inactive uveitis status after 1, 3, and 6 months in a higher percentage of cases. However, the obtained data still require additional clinical confirmation.

Predicting the course of uveitis against the background of juvenile idiophatic arthritis when using topical therapy regimens. The results of mathematical modeling

BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in children, and uveitis is its most destructive extra-articular manifestation. Despite the existence of Federal clinical guidelines for the management of these patients, their treatment is largely based on the experience of doctors and varies greatly even within the same country. AIM: The aim of the study is to find factors for predicting the course of uveitis and optimizing therapy. MATERIALS AND METHODS: The case histories of 150 children aged 1.5 to 17 years with active uveitis in the structure of juvenile arthritis were analyzed using multifactorial modeling (construction of classification trees). RESULTS: The fact of a significant influence of the time elapsed from the onset of rheumatic disease and uveitis until the start of therapy by genetically engineered medications (tumor necrosis factor alpha inhibitors) in treatment programs has been established. CONCLUSIONS: Thus, the inclusion of this factor into the group of controlling ones makes it possible to achieve inactive uveitis status after 1, 3, and 6 months in a higher percentage of cases. However, the obtained data still require additional clinical confirmation.

Photothermally responsive graphene hybrid dry powders for diabetic wound healing

The treatment of diabetic wounds remains a significant challenge in the medical field. In this study, we present a novel approach using photothermally responsive graphene hybrid dry powders for the treatment of diabetic wounds. These powders, derived from polyacrylic acid (PAA) and polyethyleneimine (PEI), exhibit rapid water absorption at the interface, leading to the in situ formation of physically crosslinked hydrogels due to interactions between polymers. Furthermore, by incorporating graphene into the PAA/PEI powder mixture, we establish a multifunctional platform with capabilities such as photothermal antibacterial effects and drug release. Given the outstanding performance of this hybrid material, we demonstrate its potential in wound healing by incorporating the tumor necrosis factor-alpha (TNF-α) inhibitor Etanercept into the PAA/PEI powder. This intervention resulted in a significant improvement in the wound healing process in diabetic rats, as evidenced by the downregulation of inflammatory factors, promotion of collagen deposition, and enhanced vascularization. These remarkable attributes underscore the enormous potential value of the presented hydrogel patches in the field of biomedicine.

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.

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.

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.

Novel Piperazine Derivatives as Potent Antihistamine, Anti-Inflammatory, and Anticancer Agents, their Synthesis and Characterization.

In this study, a series of novel piperazine derivatives were synthesised with high-to-good yields, and their structural analogies were confirmed using FTIR, 1H-NMR, and LC-MS techniques. The synthesised compounds were evaluated for antioxidant and antimicrobial activities. Among the four synthesised piperazine derivatives, compound PD-2 exhibited relatively good antioxidant activity, with an IC50 value of 2.396 μg/mL, while the other three derivatives showed moderate to low antioxidant activity. Furthermore, compound PD-2 displayed antimicrobial activity against Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a fungus. However, all four compounds showed strong resistance against grampositive bacteria, Staphylococcus aureus. Additionally, compound PD-1 exhibited significant antihistamine activity, eliciting an 18.22% reduction in histamine levels. Both PD-1 and PD-2 demonstrated noteworthy anti-inflammatory activity in a dosedependent manner (5-10μM), leading to the inhibition of nitrite production up to 39.42% and 33.7% at higher concentrations (10 μM) and inhibition of tumour necrosis factor-alpha (TNF-α) generation up to 56.97% and 44.73% at 10 μM, respectively. Additionally, both novel molecules PD-1 and PD-2 effectively restrained the growth of HepG2 cells in a manner that is dependent on the dosage up to 55.44% and 90.45% at the highest concentrations (100 μg/mL), respectively. These findings substantiate the rationale for further investigation into the novel series of persuasive piperazine analogues as potential agents with anti-inflammatory, antihistamine and anticancer properties.

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.

Development of anti-MDA5 autoantibody-positive dermatomyositis following the use of etanercept biosimilar in rheumatoid arthritis.

The induction of autoimmune diseases during tumor necrosis factor-alpha inhibitor (TNFi) usage has been described. Herein, we report a rare case of a 49-year-old woman with anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM), which developed five weeks after the introduction of an etanercept biosimilar to rheumatoid arthritis (RA). Four of the five known cases, including ours, of anti-MDA5Ab positive DM complicated with RA revealed anti-MDA5Ab positive DM following TNFi usage. When patients with RA are diagnosed with interstitial lung disease during TNFi usage, anti-MDA5 Ab-positive DM could be a differential diagnosis.

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

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

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.

Secukinumab after first-line tumor necrosis factor-alpha inhibitor therapy in psoriatic arthritis: A real-world retrospective cohort study.

This study compared the secukinumab treatment responses and adverse effects in psoriatic arthritis patients who received secukinumab as second-line with those that received secukinumab after two or more tumor necrosis factor-alpha (TNF-α) inhibitors. The retrospective study included 68 psoriatic arthritis patients followed up between October 2018 and October 2021. The patients were divided into two groups according to their anti-TNF-α treatment history. Group 1 consisted of 29 patients (11 males, 18 females; mean age: 45.3±13.3 years; range, 21 to 69 years) who had previously received one anti-TNF-α agent, while Group 2 included 39 patients (18 males, 21 females; mean age: 46.4±13.0 years; range, 24 to 70 years) who had been treated with two or more anti-TNF-α agents. Treatment responses of the groups were measured and compared using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Visual Analog Scale (VAS). A posttreatment BASDAI score ≤4 was used as a criterion for remission. The mean duration of secukinumab treatment was 16.6±12.7 months for Group 1 and 16.0±11.6 months for Group 2 (p=0.84). Both groups responded significantly to secukinumab in terms of BASDAI and VAS scores (p<0.001 and p<0.001, respectively). Group 1 had a greater decline in BASDAI and VAS scores than Group 2 (p=0.045 and p=0.032, respectively). Furthermore, the remission rate was greater in Group 1 compared to Group 2 (58% vs. 34%, p=0.03). The adverse effects of secukinumab treatment were an allergic reaction in Group 1 and one case of ulcerative colitis in Group 2. Second-line secukinumab treatment resulted in a greater decline in BASDAI and VAS scores. Moreover, secukinumab achieved a significantly higher rate of remission when it was used as second-line therapy after one anti-TNF-α agent.