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BackgroundIxekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is indicated for psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis.Literature highlights efficacy and safety in real life in patients affected by psoriasis[1], instead little are data concerning PsA.[2]ObjectivesTo retrospectively evaluate the effectiveness and safety of ixekizumab, in a cohort of patients with PsA.MethodsPatients with a diagnosis of PsA and treated with ixekizumab who visited our outpatient clinic from October 2019 to December 2022 were included in the study. Clinical data were recorded since the first prescription of ixekizumab and at 6-month follow-up visit. Demographic, clinical and laboratory characteristics, treatment, and causes of discontinuation were analyzed. Differences between baseline and 6-months erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count (TJC) and swollen joint count (SJC) were analysed.ResultsMain results are reported on Table 1. 76 patients were included in the study, with an average age at the prescription of ixekizumab (T0) of 57.1±13.0 years.Main comorbidities were: hypertension (44.7%), obesity and overweight (44.7%), cardiopathy (19.7%), hepatic steatosis (21.0%), diabetes (13.2%), and hyperlipemia (3.9%). 93.42% of patients presented peripheral arthritis, 30.6% axial involvement, and 42.1 % enthesitis.28,9% of patients were biologic-naïve, 34,0% received one biologic agent before, and 31.5% two or more biologic agents. 88,2% of patients initiated ixekizumab in combination with a csDMARDs, mainly methotrexate.The indications for the prescription of ixekizumab as a first biologic agent were: multiple comorbidities, severe psoriasis, and intolerance to csDMARDs.28.9% of patients stopped ixekizumab because of primary failure (31.8%), secondary failure (22.7%), or adverse events (45.5%). 40% of the adverse events were relevant skin reactions at the injection site. No severe adverse events were registered.60 patients completed 6 months of treatment (T6). In those patients, a statistically significant decrease between the SJC and TJC at baseline and T6 was found (p-value 0.0011 and 0.0006 respectively). No difference in the values of ESR and CRP values between T0 and T6 was present.ConclusionThere are few data in real life concerning efficacy and safety in patients affected by PsA. In our cohort, ixekizumab significantly improved peripheral arthritis, and it revealed a good safety profile, without severe adverse events during the follow up. Further real-life evaluations on axial involvement, which was not included in this study, are warranted.References[1]Malagoli P. et al. Real life long-term efficacy and safety of ixekizumab in moderate-to-severe psoriasis: A 192 weeks multicentric retrospective study-IL PSO (Italian landscape psoriasis). Dermatol Ther. 2022[2]Manfreda V. et al. Efficacy and safety of ixekizumab in psoriatic arthritis: a retrospective, single-centre, observational study in a real-life clinical setting. Clin Exp Rheumatol. 2020Table 1.General characteristics of our cohort and clinical and laboratory findings at baseline and follow-up for patients who completed 6 months of treatment with ixekizumab.Male/female n. (%)22 (28.9%)/54 (71.1%)Mean age at diagnosis (years)50.0Years from diagnosis at the first prescription of ixekizumab (years)6.7Patients: n. 60T0T6p-valueESR (mm/h)27.44±23.327.56±22.20.9741CRP (mg/dl)1.58±2.470.98±1.70.1569TJC9.17±6.985.02±6.650.0011SJC1.57±2.750.28±0.640.0006Acknowledgements:NIL.Disclosure of InterestsElisa Bellis Consultant of: Bristol-myers Squibb Srl - Temas, Grant/research support from: Pfizer, DENISE DONZELLA: None declared, Gloria Crepaldi Speakers bureau: Eli-Lilly, BMS, Consultant of: Galapagos, Janssen, Valeria Data: None declared, Marinella Gammino: None declared, Valeria Guardo: None declared, Claudia Lomater Speakers bureau: Eli-Lilly, Janssen, Formedica, Bristol-myers, Elena Marucco: None declared, Marta Saracco: None declared, Annamaria Iagnocco Speakers bureau: Abbvie, MSD, Alfasigma, Celltrion, BMS, Celgene, Eli-Lilly, -Sanofi Genzyme, Pfizer, Galapagos, Gilead, Novartis, SOBI, Janssen, Consultant of: Abbvie, MSD, Alfasigma, Celltrion, BMS, Celgene, Eli-Lilly, -Sanofi Genzyme, Pfizer, Galapagos, Gilead, Novartis, SOBI, Janssen, Grant/research support from: Pfizer, Abbvie.

BackgroundEsophageal involvement is common in dermatomyositis (DM), occurring in up to 54% of patients [1]. It can lead to severe complications, such as malnutrition and aspiration pneumonia. Therefore, esophageal assessment is of foremost importance to drive patients management. Recently, high-resolution impedance manometry (HRiM) has emerged as a promising technique to assess esophageal motility and has already been tested in systemic sclerosis [2].ObjectivesTo evaluate esophageal motility by HRiM in DM and correlate the alterations to clinical and serological disease domains.MethodsWe analyzed HRiM findings in 15 consecutive DM patients enrolled in our clinic between December 2021 and December 2022. All patients received a rheumatological assessment, including screening questions for dysphagia, and underwent HRiM. All HRiM parameters (Integrated relaxation pressure (IRP), percentage of LES relaxation, distal contractile integral (DCI), distal latency (DL), upper esophageal sphincter (UES) pressure) were studied, coupled with impedance findings (esophageal clearing and bolus transit time). The report followed the Chicago Classification v.4.0 for esophageal motility disorders. The associations between HRiM findings and DM features were evaluated.ResultsDM patients were divided according to their serological status: 5 Mi2 (33%), 6 MDA5 (40%), 2 Ku (13%), 1 NXP2 (6.6%), 6 Ro52 (40%). Asymptomatic patients presenting at least one HRiM alterations were 4 (26.7%). Among HRiM parameters, 83.3% MDA5 patients and 50% Ro52 patients showed high UES pressure (Figure 1), in contrast to the other serological groups. Among impedance findings, incomplete bolus clearance was detected in MDA5 (67%) and in Ro52 patients (50%). Notably, the only NXP2 patient showed 100% of incomplete bolus clearance. Considering the Chicago classification v.4.0, only 16.7% of MDA5 patients had a normal esophageal motility, the rest presenting absent contractility (33.3%) and ineffective esophageal motility (IEM) (50%). Distal esophageal spasm was evidenced only in Mi2 patients (40%). All patients with concomitant manometric and impedance alterations were MDA5 positive. DM patients with high UES, IEM or impedance abnormalities presented higher rate of lung involvement and active Raynaud’s phenomenon (Table 1). No relation with ongoing treatment emerged.ConclusionWe describe for the first time HRiM findings in DM. Anti-MDA5 patients appear to have a more severe esophageal involvement, even in absence of reported dysphagia, followed by anti-Ro52 patients. Interestingly, the same subsets show higher prevalence of lung involvement and Raynaud’s phenomenon, suggesting a possible pathogenetic link between esophageal, lung and microvascular disease. Asymptomatic patients may present occult esophageal motility disorders detected by HRiM. Further validation of our findings are required to definitely include HRiM in the workup of DM patients as a diagnostic, prognostic and monitoring tool.References[1]Ebert EC. Review article: the gastrointestinal complications of myositis. Alimentary Pharmacology & Therapeutics. 2010[2]Vettori S et al. Esophageal high-resolution impedance manometry alterations in asymptomatic patients with systemic sclerosis: prevalence, associations with disease features, and prognostic value. Clin Rheumatol. 2018Figure 1.Representative HRiM plot of a MDA5+ patientTable 1.HRiM abnormalities and features of DM patientsHigh UES(n = 6)IEM(n = 3)Incomplete bolus clearance/altered flow time(n = 7)Combination(n = 3)Anti-Mi22 (33.3%)0 (0%)0 (0%)0 (0%)Anti-MDA55 (83.3%)3 (100%)4 (57.1%)3 (100%)Anti-Ro523 (50%)1 (33.3%)3 (42.8%)1 (%)Anti-Ku1 (16.6%)1 (33.3%)1 (14.3%)1 (33.3%)Anti-NXP20 (0%)0 (0%)1 (14.3%)0 (0%)DLCO < 80% predicted5 (83.3%)3 (100%)6 (85.7%)3 (100%)ILD4 (66.6%)3 (100%)4 (57.1%)3 (100%)Dysphagia2 (33.3%)1 (33.3%)3 (42.8%)1 (33.3%)Raynaud’s phenomenon4 (66.6%)2 (66.6%)6 (85.7%)2 (66.6%)Acknowledgements:NIL.Disclosure of InterestsChiara Rizzo: None declared, Lidia La Barbera: None declared, FEDERICA CAMARDA: None declared, DENISE DONZELLA: None declared, Gabriele Barletta: None declared, Sebastiano Bonventre: None declared, Giuliana Guggino Speakers bureau: Pfizer, Novartis, Celgene, Abbvie, Roche, Lilly, Janssen, UCB.

Background:Addition of biologic drugs to standard of care (SoC) in systemic lupus erythematosus (SLE) is advised in refractory patients. Evidence is needed on the effectiveness of early biologic use in influencing SLE course.Objectives:To assess the effect of belimumab administration on disease progression in early active lupus patients.Methods:We performed a multicentric observational study on patients with early SLE receiving either belimumab or SoC alone and compared the rate of EULAR/ACR 2019 criteria [1] accrual between the two groups as a measure of lupus progression over time. Patients were defined as early active if they were diagnosed within 12 months from treatment initiation and displayed up to two EULAR/ACR clinical criteria, excluding major organ involvement, with active serology (i.e. positive anti-dsDNA antibodies and/or decreased serum complement). Clinical, demographic and serological data were collected in an anonymized fashion at baseline and at 3, 6, and 12 months. Kaplan-Meier curves with log-rank comparison were used to assess criteria accrual throughout the first 12 month of follow-up.Results:We included 57 early active SLE patients, 24 (42.1%) receiving SoC alone and 33 (57.9%) receiving add on belimumab to SoC and followed up for at least 12 months from baseline. The groups were comparable in terms of age, gender, disease duration, background immunosuppression and overall disease activity at baseline. Patients doomed to early belimumab displayed higher mean SLICC and prednisone daily dosage (Table 1).Overall, 8.7 events/100-patients years occurred in our cohort. Twenty-five percent of patients on SoC versus 3.2% of patients on early belimumab accrued at least one EULAR/ACR criterion throughout the follow-up (p=0.035). Patients on SoC displayed development of skin rash (2 cases), arthritis (1 case), lupus nephritis (1 case), while one case of pericarditis occurred in the belimumab group.Criteria-free survival was significantly longer in patients receiving belimumab early as compared to those receiving SoC alone (log-rank 5.78, p=0.016) Figure 1. Mean time-to-event (months) was shorter in patients on SoC alone (10.3± 3.33 vs. 11.8±1.07, p=0.027).Conclusion:Timely use of belimumab in patients with early active SLE can significantly delay disease progression, potentially preventing development of severe manifestations.REFERENCES:[1] Aringer M, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol 2019;71:1400-1412. doi: 10.1002/art.40930.Table 1.Baseline clinical and demographic features of early SLE patientsBelimumabSoCPAge34.05±11.6038.65±11.120.141Gender, F (%)29 (87.9)23 (95.8)0.385HCQ n (%)30 (90.9)17 (70.8)0.077IS n (%)26 (78.8)21 (87.5)0.494Prednisone mg/d8.75±6.675.00±10.610.054Anti-dsDNA titers (kU/L)201.04±282.9588.91±46.860.020C3 mg/dl79.54±27.4182.48±23.910.348C4 mg/dl12.00±5.1210.77±3.530.180cSLEDAI-2K5.42±1.765.75±1.330.227SLICC-DI0.12±0.420.00±0.000.052Continuous variables expressed as mean±SD. HCQ, hydroxycholoroquine; IS, immunosuppressants; cSLEDAI-2K, clinical SLE-activity index 2000; SLICC-DI, SLICC damage indexFigure 1.Kaplan-Meier curves depicting criteria-free survival in patient groupsAcknowledgements:NIL.Disclosure of Interests:Mariele Gatto GSK, AstraZeneca, Janssen, Matilde Caria: None declared, Claudio Cruciani: None declared, Pietro Francesco Gavino Pilo: None declared, Elisa Bellis BMS, Denise Donzella Janssen, Roberto Depascale: None declared, Daniela Rossi: None declared, Dario Roccatello: None declared, Andrea Doria GSK, AstraZeneca, Pfizer, Celgene, Eli Lilly, BMS, Roche, Annamaria Iagnocco Abbvie, Alfasigma, BMS, Celgene, Celltrion, Eli Lilly, Galapagos, Gilead,Janssen, MSD, Novartis, Pfizer, Sanofy Genzyme, SOBI, Abbvie, Pfizer, Novartis, Savino Sciascia: None declared.

Background:Secukinumab is a human monoclonal antibody that selectively binds interleukin 17A, inhibiting its interaction with the interleukin 17 receptor and is prescribed for the treatment of psoriatic arthritis (PsA), plaque psoriasis, ankylosing spondylitis, axial spondyloarthritis, and juvenile idiopathic arthritis.Objectives:To retrospectively evaluate the drug retention rate (DRR) of secukinumab in a monocentric cohort of patients affected by spondyloarthritis.Methods:Patients with a diagnosis of spondyloarthritis and treated with secukinumab who were evaluated at our outpatient clinic from January 2017 to February 2023 were included in the study. Demographic, clinical characteristics, and comorbidities were recorded. DRR was evaluated by Kaplan-Meier method as time to drug discontinuation, and baseline factors predicting drug discontinuation were investigated through Cox regression after adjusting for baseline confounders.Results:One-hundred-seventy-eight patients were included in the study, with a median follow-up of 20.5 (IQR 10-39) months. Among these, 64.6% of patients were female, and 9.7% tested positive for HLAB27. 69.7% of patients presented peripheral involvement, 52.2% axial involvement, 40.4% enthesitis, and 52% psoriasis. Comorbidities were observed in 65.2% of patients, with the most common being hypertension (34.8%), cardiovascular diseases (18.5%), hepatic steatosis (22.5%), diabetes (11.8%), hyperlipemia (23%), kidney disease (6.2%), and a personal history of cancer (10.1%). The multivariable analysis identified the number of previous targeted synthetic or biological DMARD (ts/b DMARDs) (HR 1.44, 95% CI 1.01-2.06), hypertension at baseline (HR 2.56, 95% CI 1.08-6.11), and body mass index (BMI) (HR 1.08, 95% CI 1.01-1.17) as independent predictors of drug discontinuation. In contrast, old age at diagnosis was associated with a lower risk of discontinuation (HR 0.96, 95% CI 0.92-0.99) (Table 1). The drug retention rate at 12, 24 and 48 months was 79.4%, 69.3%, 55% respectively (Figure 1, panels A and B).Conclusion:In our cohort, secukinumab revealed a good DRR. An old age at diagnosis seemed to be protective against withdrawal, whereas the number of previous ts/b DMARDs, hypertension at baseline, and BMI were identified as predictors of drug discontinuation. Further studies are needed to confirm our findings.Table 1.Predictors of secukinumab withdrawal (Cox regression)VariableHR (95%CI)P valueNumber of previous ts/b DMARDs1.44 (1.01-2.06)0.045Hypertension2.56 (1.08-6.11)0.033BMI1.08 (1.01-1.17)0.036Age at diagnosis0.96 (0.92-0.99)0.038Variables in the model: gender, age at diagnosis, BMI, disease duration before secukinumab, number of previous ts/b DMARDs, psoriasis, SPA phenotype.Figure 1.Secukinumab retention rate.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Elisa Bellis BMS, Mariele Gatto GSK, Astrazeneca, Janssen, GSK, Denise Donzella Janssen, Gloria Crepaldi Janssen, Galapagos, Eli Lilly, BMS, Novartis, Abbvie, Alfasigma, Valeria Data: None declared, Silvia Di Gregorio: None declared, Marinella Gammino: None declared, Valeria Guardo: None declared, Claudia Lomater Abbvie, BMS, Janssen, Eli Lilly, Novartis, Pfizer, Gaetano Liperoti: None declared, Elena Marucco: None declared, Ginevra Pastorin: None declared, Silvia Perrone: None declared, Marta Saracco: None declared, Annamaria Iagnocco Abbvie, Alfasigma, BMS, Celgene, Celltrion, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofy Genzyme, SOBI, Abbvie, Pfizer, Novartis.

Objective. The journey to a diagnosis of spondyloarthritis (SpA) can be difficult for women, who often experience delays in receiving the correct diagnosis as their symptoms are frequently misinterpreted due to other conditions like osteoarthritis, fibromyalgia, or other psychosomatic disorders. The purpose of this article is to examine the challenges in the diagnosis of SpA in women and the possible role of musculoskeletal ultrasound in early diagnosis and in avoiding misdiagnosis. Methods. We have performed a narrative review of the currently available literature on the subject. Results. The complexity of diagnosing SpA in women is compounded by the misconception that the disease predominantly affects men. To facilitate early diagnosis and prevent misdiagnosis, it is crucial not to overlook gender differences in the clinical presentation of SpA. Since women have more peripheral and enthesitic involvement, performing an ultrasound of entheses, tendons, and joints in women with musculoskeletal symptoms that could refer to SpA may help both in the early and differential diagnosis. Conclusions. There is a need to increase awareness among physicians of the existence of a different clinical presentation of SpA between men and women. The use of musculoskeletal ultrasound, which allows the detection of even subclinical inflammation and structural damage since early disease at the level of joints, tendons, and entheses can help make an early diagnosis and avoid misdiagnosis. Early diagnosis and timely treatment of SpA are crucial to reducing irreversible damage.

Background Early-life adversity that increases the risk of growth stunting is hypothesized to increase the risk of obesity and, in girls, early-onset puberty. This hypothesis was tested in children adopted from orphanages. Methods Post-institutionalized (PI) youth were compared with youth reared in comparable families (non-adopted; NA) on height, weight, pubertal stage, and fat mass (127 PI, 80 female; 156 NA, 85 female, aged 7–14 years). Anthropometric findings at adoption were obtained from first US clinic visits. Results Overall, 25% of PI youth were height-stunted (<3rd percentile) at adoption. Years post adoption, PI youth had lower BMI-for-age ( P =0.004), height-for-age ( P <0.001), and less body fat ( P <0.001) than NA youth had, but they did not differ by sex. Pubertal status did not differ by group or sex. The anthropometric findings held when the stunted-at-adoption subset was examined; they were also less likely to be in central puberty than other PI youth. Conclusion Early deprived orphanage care increases the risk of growth stunting but not obesity in children adopted into US families, and it does not independently contribute to early-onset puberty for PI girls. The role of the environment following early adversity may modify the impact of early adverse care.

The bicyclam AMD3100 (formula weight 830) blocks HIV-1 entry and membrane fusion via the CXCR4 co-receptor, but not via CCR5. AMD3100 prevents monoclonal antibody 12G5 from binding to CXCR4, but has no effect on binding of monoclonal antibody 2D7 to CCR5. It also inhibits binding of the CXC-chemokine, SDF-1α, to CXCR4 and subsequent signal transduction, but does not itself cause signaling and has no effect on RANTES signaling via CCR5. Thus, AMD3100 prevents CXCR4 functioning as both a HIV-1 co-receptor and a CXC-chemokine receptor. Development of small molecule inhibitors of HIV-1 entry is feasible.

This study is a process evaluation of a clinical–community partnership that implemented evidence-based interventions in clinical safety net settings. Adoption and implementation of evidence-based interventions in these settings can help reduce health disparities by improving the quality of clinical preventive services in health care settings with underserved populations. A clinical–community partnership model is a possible avenue to catalyze adoption and implementation of interventions amid organizational barriers to change. Three Federally Qualified Health Centers in South Los Angeles participated in a partnership led by a local community-based organization (CBO) to implement hypertension interventions. Qualitative research methods were used to evaluate intervention selection and implementation processes between January 2014 and June 2015. Data collection tools included a key participant interview guide, health care provider interview guide, and protocol for taking meeting minutes. This case study demonstrates how a CBO acted as an external facilitator and employed a collaborative partnership model to catalyze implementation of evidence-based interventions in safety net settings. The study phases observed included initiation, planning, and implementation. Three emergent categories of organizational facilitators and barriers were identified (personnel capacity, professional development capacity, and technological capacity). Key participants and health care providers expressed a high level of satisfaction with the collaborative and the interventions, respectively. The CBO’s role as a facilitator and catalyst is a replicable model to promote intervention adoption and implementation in safety net settings. Key lessons learned are provided for researchers and practitioners interested in partnering with Federally Qualified Health Centers to implement health promotion interventions.