AB0032 DIFFERENTIAL IMPACT OF BIOLOGICS AND GLUCOCORTICOIDS ON TNF SECRETION AND CD14+CD16+ MONOCYTES PERCENTAGE IN CULTURE DERIVED FROM SYNOVIAL FLUIDS OF PATIENTS WITH PSORIATIC ARTHRITIS-IN VITRO RESEARCH

Background:Inflammatory joint diseases, such as psoriatic arthritis (PsA), are frequently treated by biologics. Assessment of treatment efficacy is based upon change in clinical activity scores and in tender and swollen joint counts. Although the response to these agents may be attributed to their central anti-inflammatory effects, synovial response may be operating in parallel. The potential beneficial role of intra-articular injection of tumor necrosis factor (TNF) blockers compared to glucocorticoids (GCs) in reducing synovitis was shown by means of clinical and instrumental validated measures (1). The inflamed synovial fluid is rich in mononuclear cells, however, the different mode of action of the in vitro response of these cells to drugs may contribute to the understanding of cellular response to therapeutic agents in central as opposed to peripheral compartments.Objectives:To evaluate the effect of biologics used in the management of PsA on synovial fluid mononuclear cells (SFMCs) in vitro, and to compare their modes of action to GCs that are used to locally alleviate synovial inflammation.Methods:SFMCs were obtained from PsA patients (n=11) during therapeutic knee arthrocentesis. The cells were cultured in vitro for 7 days in the presence of biologics (adalimumab, infliximab, secukinumab and ustekinumab, 10ug/ml) and GCs (betamethasone and methylprednisolone, 1 ug/ml and 10ug/ml) or medium as control. Levels of the secreted TNF were measured by ELISA. Changes in %CD14+CD16+ monocytes were analyzed by flow cytometry.Results:Both TNF inhibitors (adalimumab p&lt;0.01, infliximab p=0.0003) and GCs (betamethasone and methylprednisolone at 1ug/ml p&lt;0.01 and at 10ug/ml p&lt;0.04) significantly reduced TNF levels in cultured media derived from SFMCs of PsA patients (n=8) compared to medium. None of the other biologics reduced TNF levels in culture (Fig. 1A). Additionally, %CD14+CD16+ SFMCs derived from PsA patients (n=11) were significantly reduced by TNF inhibitors (p=0.0003) compared to medium, however, other biologics and GCs did not display similar activity (Fig. 1B).Figure 1.Both TNF inhibitors and GCs block TNF secretion but exhibit different activity on inflammatory CD14+CD16+ monocytes derived from SFMCs of PsA patients. SFMCs were co-cultured for 7 days in the presence of adalimumab, infliximab, secukinumab and ustekinumab at 10ug/ml or with betamethasone and methylprednisolone at 1ug/ml and 10ug/ml. Medium alone was used as a control. (A) Culture supernatants were analyzed for TNF levels by ELISA (n=8). (B) Cells were analyzed for %CD14+CD16+ monocytes by flow cytometry (n=11). All p values were calculated by the non-parametric one-way ANOVA Kruskal-Wallis test and Dunn’s multiple comparison test, *p&lt;0.04, **p&lt;0.01 and ***p=0.0003.Conclusion:Our data demonstrated marked activity mediated by TNF inhibitors in comparison with other biologics tested for their ability to suppress TNF secretion and inflammatory CD14+CD16+ monocytes. In contrast, GCs suppressed TNF secretion but did not significantly change the proportion of inflammatory CD14+CD16+ monocytes. These findings suggest an additional mechanism of action exerted directly by TNF inhibitors on synovial monocytes and which differs from that of GCs. These results warrant further studies of the therapeutic potential of local peripheral activity of TNF inhibitors for clinical application.Reference:[1]Carubbi F, Zugaro L, Cipriani P, Conchiglia A, Gregori L, Danniballe C, et al. Safety and efficacy of intra-articular anti-tumor necrosis factor alpha agents compared to corticosteroids in a treat-to-target strategy in patients with inflammatory arthritis and monoarthritis flare. Int J Immunopathol Pharmacol. 2016;29:252-66.Disclosure of Interests:None declared</jats:sec

TikTok as a Platform for Marketing Campaigns: The effect of Brand Awareness and Brand Recall on the Purchase Intentions of Millennials

Modern individuals create social networks to connect. A digital social landscape now exists within the society that enables interactions while providing convenience and efficiency. A social media platform called TikTok consists of comprehensive and diverse videos that empower users to upload and watch content as they desire. The researchers highly considered this feature which led them to explore the deliverance of marketing campaigns created on TikTok. In a more profound sense, since countless brands are scrutinizing TikTok to gather their consumers, the purpose and objectives of this study determined the effect of brand awareness and brand recall on the purchase intention of millennials. This study incorporated the Attention, Interest, Desire, and Action (AIDA) Model and Selective Exposure Theory (SET) to serve as the foundation of the analysis. The study employed descriptive causal analysis. The study surveyed a group of millennials, ranging from 25 to 40 years old, who currently reside in the Philippines' National Capital Region (NCR). The researchers distributed the survey through Google forms and then utilized frequency and percentage distribution, mean and standard deviation, and PLS-SEM to analyze the results. This study determined that marketing campaigns can largely input brand awareness among millennials compared to enhancing their brand recall. Furthermore, marketing campaigns trigger their purchase intention. This study is deemed a resource to business owners, marketing students and professionals, and academic institutions that hope to generate further information on the existence of TikTok and its marketing advantage.</jats:p

TikTok as a Platform for Marketing Campaigns: The effect of Brand Awareness and Brand Recall on the Purchase Intentions of Millennials

Modern individuals create social networks to connect. A digital social landscape now exists within the society that enables interactions while providing convenience and efficiency. A social media platform called TikTok consists of comprehensive and diverse videos that empower users to upload and watch content as they desire. The researchers highly considered this feature which led them to explore the deliverance of marketing campaigns created on TikTok. In a more profound sense, since countless brands are scrutinizing TikTok to gather their consumers, the purpose and objectives of this study determined the effect of brand awareness and brand recall on the purchase intention of millennials. This study incorporated the Attention, Interest, Desire, and Action (AIDA) Model and Selective Exposure Theory (SET) to serve as the foundation of the analysis. The study employed descriptive causal analysis. The study surveyed a group of millennials, ranging from 25 to 40 years old, who currently reside in the Philippines' National Capital Region (NCR). The researchers distributed the survey through Google forms and then utilized frequency and percentage distribution, mean and standard deviation, and PLS-SEM to analyze the results. This study determined that marketing campaigns can largely input brand awareness among millennials compared to enhancing their brand recall. Furthermore, marketing campaigns trigger their purchase intention. This study is deemed a resource to business owners, marketing students and professionals, and academic institutions that hope to generate further information on the existence of TikTok and its marketing advantage

Late-Onset Spondylarthritis Presenting as Glucocorticoid-Resistant Polymyalgia Rheumatica: A hitherto underappreciated entity where TNF or IL-17 Blockade may have a Therapeutic Role

Background Polymyalgia rheumatica (PMR) is an age-related inflammatory disease with shoulder-hip girdle involvement. Magnetic resonance imaging (MRI) reveals extracapsular/entheseal soft tissue involvements in both PMR and spondyloarthritis (SpA) with sacroiliac joint and peri-entheseal spinal bone marrow oedema (BMO) being characteristic of SpA. Therefore, some shared anatomical topography might be expected to result in similar clinical features. Herein we describe the clinical and imaging features of SpA initially diagnosed as PMR. Methods Patients followed at Leeds Teaching Hospitals NHS Trust with a diagnosis of psoriatic arthritis (PsA), or axial SpA (axSpA) were screened to identify those initially diagnosed with PMR from 2002 to 2024. Only those patients who retrospectively fulfilled the 2012 EULAR/ACR classification criteria or the Bird criteria for PMR were included. Clinical data relevant to initial PMR diagnosis, imaging features, follow-up and treatment data were collected, as well as radiographic or MRI features that established the final diagnosis. Results Thirty-one patients [median age in years (IQR): 62 (58–69); 17 females and 14 males] presenting with typical PMR shoulder/hip girdle pain were subsequently classified as SpA-spectrum disorders. The SpA diagnosis was made in 12 patients within three months of presentation, and in 19 patients during the remaining follow-up period [median (IQR): 3 (1–4) years]. Four of 27 tested patients were HLA-B27 positive. BMO on MRI was detected in the spine and/or sacroiliac joints in 20 of 25 imaged patients (80%) (sacroiliac joint: 17 patients [68%], spine: 15 patients [60%]). Clinical resolution with CRP normalisation occurred in 21 of 31 patients following initial glucocorticoid (GC) therapy, but 7 of these 21 initial responders experienced disease flares or CRP elevations. Therapy-wise, disease-modifying antirheumatic drugs (DMARDs) were used in 21 of 31 cases: 8 received conventional DMARDs, and 11 received biologic agents (eight anti-TNFs, three IL-17 inhibitors), while the remaining 10 patients were treated with 10 mg/day or less GC therapy. Conclusion Late-onset SpA with PMR clinical presentations is characterised by failure to respond to or taper GC therapy and is often identified by SpA-specific osteitis patterns on MRI. We propose that a PMR-SpA overlap may account for biological therapy efficacy in steroid-refractory PMR

LB0003 IMMUNOGENICITY AND SAFETY OF THE BNT162b2 mRNA COVID-19 VACCINE IN ADULT PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES AND GENERAL POPULATION: A MULTICENTER STUDY

Background:Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity, efficacy, and safety of the novel BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.Objectives:To investigate the immunogenicity, efficacy, and safety of the BNT162b2 mRNA vaccine in patients with AIIRD compared to the general population.Methods:A prospective multicenter study investigated immunogenicity, efficacy, and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthropathy (axSpA), systemic lupus erythematosus (SLE), connective tissues diseases (CTD), systemic vasculitides, and idiopathic inflammatory myositis (IIM), compared to control subjects without rheumatic diseases or immunosuppressive therapies. Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2 - 6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/ml. Post-vaccination efficacy defined as post-vaccination COVID-19 infection and safety were assessed. Pre- and post- vaccination disease activity indices were assessed as appropriate for each disease.Results:A total of 686 AIIRD patients and 121 controls participated into the study. AIIRD patients were significantly older than controls, mean age±SD 56.76±14.88 vs 50.76±14.68, respectively, p&lt;0.0001. A total of 95.2% (n=653) AIIRD patients were treated with immunomodulatory medications.The seropositivity rate was 86% (n=590) in patients with AIIRD compared to 100% in controls (p &lt;0.0001) The level of the S1/S2 antibodies was significantly reduced in AIIRD patients compared to controls (mean± SD 132.9±91.7 vs 218.6±82.06, P&lt;0.0001). In patients with PsA, AxSpA, SLE, and LVV, the seropositive rate was above 90%. In RA, the seropositive rate was 82.1% and the lowest seropositive rate (&lt;40%) was observed in patients with AAV and IIM.Anti-CD20 significantly impaired the vaccine’s immunogenicity, with the lowest seropositivity rate of 39%. The use of GC, mycophenolate mofetil (MMF), and abatacept was associated with a significantly lower rate of seropositivity (Figure 1). MTX significantly reduced the seropositivity in patients treated with MTX monotherapy and in combinations with other treatments (92% and 84%, respectively), although at a lesser magnitude than anti-CD20, MMF, and abatacept. More than 97% of patients treated with anti-cytokine therapies including TNFi, interleukin-17 and interleukin-6 inhibitors had an appropriate immunogenic response when used as monotherapy. The combination of TNFi with MTX significantly reduced the rate of seropositivity to 93%, p=0.04. Age over 65 years, a diagnosis of RA, IIM, ANCA-associated vascilitis, and treatment with GC, MMF, anti-CD20, and abatacept were associated with a reduced likelihood of seropositivity.Figure 1.Seropositivity rate by immunosuppressive treatment.There were no post-vaccination symptomatic cases of COVID-19 among AIIRD patients and one mild case in the control group. Major adverse events in AIIRD patients included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Post-vaccination disease activity remained stable in the majority of patients.Conclusion:Vaccination with the BNTb262 vaccine resulted in an adequate immunogenic response with an acceptable safety profile in the majority of patients with AIIRD. Treatment with GC, rituximab, MMF, and abatacept may impair BNT162b2-induced immunogenicity. Postponing administration of rituximab, when clinically feasible, seems to be reasonable to improve vaccine-induced immunogenicity. Holding treatment with abatacept and MMF may be considered on an individual basis.Disclosure of Interests:None declared</jats:sec