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Almost all commercial proteins are purified using ammonium sulfate precipitation. Protein-polymer conjugates are synthesized from pure starting materials, and the struggle to separate conjugates from polymer, native protein, and from isomers has vexed scientists for decades. We have discovered that covalent polymer attachment has a transformational effect on protein solubility in salt solutions. Here, protein-polymer conjugates with a variety of polymers, grafting densities, and polymer lengths are generated using atom transfer radical polymerization. Charged polymers increase conjugate solubility in ammonium sulfate and completely prevent precipitation even at 100% saturation. Atomistic molecular dynamic simulations show the impact is driven by an anti-polyelectrolyte effect from zwitterionic polymers. Uncharged polymers exhibit polymer length-dependent decreased solubility. The differences in salting-out are then used to simply purify mixtures of conjugates and native proteins into single species. Increasing protein solubility in salt solutions through polymer conjugation could lead to many new applications of protein-polymer conjugates. Therapeutic proteins are often conjugated with polymers, but separating the conjugate from unconjugated protein and free polymer is a major challenge. Here, the authors discover that proteins conjugated to charged or zwitterionic polymers maintain solubility in 100% ammonium sulfate, greatly simplifying purification.

The pathogenic mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) are not fully understood. In this study, we aimed to assess the relationship between endoplasmic reticulum (ER) stress and autophagy in human and mouse hepatocytes during NAFLD. ER stress and autophagy markers were analyzed in livers from patients with biopsy-proven non-alcoholic steatosis (NAS) or non-alcoholic steatohepatitis (NASH) compared with livers from subjects with histologically normal liver, in livers from mice fed with chow diet (CHD) compared with mice fed with high fat diet (HFD) or methionine-choline-deficient (MCD) diet and in primary and Huh7 human hepatocytes loaded with palmitic acid (PA). In NASH patients, significant increases in hepatic messenger RNA levels of markers of ER stress (activating transcription factor 4 ( ATF4 ), glucose-regulated protein 78 ( GRP78 ) and C/EBP homologous protein ( CHOP )) and autophagy ( BCN1 ) were found compared with NAS patients. Likewise, protein levels of GRP78, CHOP and p62/SQSTM1 (p62) autophagic substrate were significantly elevated in NASH compared with NAS patients. In livers from mice fed with HFD or MCD, ER stress-mediated signaling was parallel to the blockade of the autophagic flux assessed by increases in p62, microtubule-associated protein 2 light chain 3 (LC3-II)/LC3-I ratio and accumulation of autophagosomes compared with CHD fed mice. In Huh7 hepatic cells, treatment with PA for 8 h triggered activation of both unfolding protein response and the autophagic flux. Conversely, prolonged treatment with PA (24 h) induced ER stress and cell death together with a blockade of the autophagic flux. Under these conditions, cotreatment with rapamycin or CHOP silencing ameliorated these effects and decreased apoptosis. Our results demonstrated that the autophagic flux is impaired in the liver from both NAFLD patients and murine models of NAFLD, as well as in lipid-overloaded human hepatocytes, and it could be due to elevated ER stress leading to apoptosis. Consequently, therapies aimed to restore the autophagic flux might attenuate or prevent the progression of NAFLD.

The enormous number of combinations of adsorbing molecules and porous materials that exist is known as adsorption space. The adsorption space for microporous polymers has not yet been systematically explored, especially when compared with efforts for crystalline adsorbents. We report molecular simulation data for the adsorptive and structural properties of polymers of intrinsic microporosity with a diverse set of adsorbate species with 345 distinct adsorption isotherms and over 240,000 fresh and swollen structures. These structures and isotherms were obtained using a sorption-relaxation technique that accounts for the critical role of flexibility of the polymeric adsorbents. This enables us to introduce a set of correlations that can estimate adsorbent swelling and fractional free volume dilation as a function of adsorbate uptake based on readily characterized properties. The separation selectivity of the 276 distinct binary molecular pairs in our data is reported and high-performing adsorbent systems are identified.

Brood parasitism imposes several fitness costs on the host species. To reduce these costs, hosts of avian brood parasites have evolved various defenses, of which egg rejection is the most prevalent. In the face of variable host-parasite mimicry and the costs of egg discrimination itself, many hosts reject only some foreign eggs. Here, we experimentally varied the recognition cues to study the underlying cognitive mechanisms used by the Chalk-browed Mockingbird (Mimus saturninus) to reject the white immaculate eggs laid by the parasitic Shiny Cowbird (Molothrus bonariensis). Immaculate eggs are the only parasite eggs rejected by this host, as it accepts all polymorphic, spotted eggs laid by cowbirds. Using a within-breeding pair experimental design, we tested for the salience of spotting, UV reflectance, and brightness in eliciting rejection. We found that the presence of spotting significantly decreased the probability of rejection while increments in brightness significantly increased rejection frequencies. The cognitive rules underlying mockingbird rejection behavior can be explained by a decision-making model which predicts changes in the levels of rejection in direct relation to the number of relevant attributes shared between host and parasite eggs.

Background:After the publication of the ORAL Surveillance trial1, the European Medical Agency (EMA) recently recommended prescribing JAK inhibitors (JAKi) in patients with rheumatoid arthritis (RA) only after an adequate risk/benefit assessment. Indeed, according to EMA recommendations, patients ≥65 year-old, former or current smokers, at high risk of developing major cardiovascular events (MACEs), thromboembolic events or cancers should receive JAKi only when other treatments, such as TNF-inhibitors, are not appropriate. Unlike randomised controlled trials, real-world data seem to be reassuring promising and, in fact, the prescription rate of JAKi has dramatically risen in the last years.Objectives:The primary objective was to assess whether being at high risk according to EMA recommendations can impact JAKi’s discontinuation rate. The secondary aim was to find out other possible predictors of JAKi’s discontinuation.Methods:This was a retrospective Italian study carried out in 22 Italian centres since 2017. All patients with RA on treatment with JAKi were included in the dataset. This cohort was subdivided into two groups: “high risk patients” and “low risk” according to EMA recommendations. The first group included patients ≥65 year-old, past or current smokers and having at least one cardiovascular or neoplastic comorbidity. The following variables were collected at baseline: sex, age, disease duration (years), smoking habit, BMI, comorbidities (diabetes, hypertension, dyslipidaemia, cancer, previous MACEs), positive RF/ACPA, associated conventional DMARDs, concomitant use of prednisone and dosage (mg/day), previous use of JAKi, discontinuation reasons, time to discontinuation (days), b/tsDMARDS naïve patients, DAS28-ESR at baseline.Results:A total of 693 patients were enrolled. 48 patients were excluded due to missing data. Overall features of our cohort are summarised in Table 1 (N=645). 372 (57.7%) patients received baricitinib, 135 (20.9%) tofacitinib, 86 (13.3%) upadacitinib and 52 (8.11%) filgotinib. 21 (3.2%). 141 (21.9%) patients discontinued JAKi after a median time of 366 days (IQR 155-914). “High-risk patients according to EMA” were the majority of our cohort (n=384, 59.5%) vs 261 “low-risk patients” (40.5%).Reasons for discontinuation were primary inefficacy (n=48, 7.4%), secondary inefficacy (n=25, 3.9%), infections (n=8, 1.2%), pulmonary embolism/deep venous thrombosis (n=6, 0.9%), cancer (n=5, 0.8%), deaths (n=2, 0.3%), and other causes (n=21, 3.3%) including remission status in 1 patient. Notably, VZV infection determined JAKi’s withdrawal in 3 patients and pulmonary embolism/deep venous thrombosis in 6 patients (all treated with baricitinib). At multivariate stepwise Cox analysis, predictors of discontinuation were: prednisone dosage [Hazard Ratio -(HR)- 1.1, 95% confidence interval- (CI)- 1.05-1.17], use of selective JAKis(HR 4.1, 95% CI 1.80-9.10), and absence of RF/ACPA (HR 0.46, 95% CI 0.26-0.83). Finally, being classified as “high risk” according to EMA was not statistically associated with JAKIs’ withdrawal (HR 1.96, 95% CI 0.96-4-01).Conclusion:Our study shows that only a minority of patients discontinued JAKi (21.9%). Notably, among discontinuation‘s causes, no MACE’s were found. Being classified at “high-risk” according to EMA was not associated with JAKi’s discontinuation. Conversely, higher prednisone dosages, treatment with selective JAKi and absence of RF/ACPA were predictors of JAKi’s withdrawal.REFERENCES:[1] Ytterberg SR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. New Engl J Med 2022;386(4):316-326.Acknowledgements:NIL.Disclosure of Interests:Maddalena Larosa UCB, ABBVIE, AMGEN, Andrea Becciolini: None declared, Simone Parisi: None declared, Eleonora Di Donato: None declared, Dario Camellino Astrazeneca, Boerhringer INgelheim, GSK, Janssen, Giuditta Adorni: None declared, Gianluca Lucchini: None declared, Daniele Santilli: None declared, Enrico Fusaro: None declared, Maria Chiara Ditto: None declared, Alberto Lo Gullo: None declared, Marino Paroli: None declared, Rosalba Caccavale: None declared, Alessandro Volpe: None declared, Antonio Marchetta: None declared, Bernd Raffeiner: None declared, Eleonora Celletti: None declared, Myriam Di Penta: None declared, Emanuela Sabatini: None declared, Francesco Cipollone: None declared, Massimo Reta: None declared, Olga Addimanda: None declared, Mirco Magnani: None declared, Elisa Visalli: None declared, Rosario Foti: None declared, Giorgio Amato: None declared, Francesco De Lucia: None declared, Roberta Foti: None declared, Antonella Farina: None declared, Francesco Girelli: None declared, Simone Bernardi: None declared, Matteo Colina: None declared, Romina Andracco: None declared, Natalia Mansueto: None declared, Giulio Ferrero: None declared, Patrizia Del Medico: None declared, Aldo Molica Colella: None declared, Veronica Franchina: None declared, Francesco Molica Colella: None declared, Federica Lumetti: None declared, Gilda Sandri: None declared, Carlo Salvarani: None declared, Dilia Giuggioli: None declared, Marta Priora: None declared, Francesca Serale: None declared, Aurora Ianniello: None declared, Valeria Nucera: None declared, Francesca Ometto: None declared, Cecilia Giampietro: None declared, Elena Bravi: None declared, Ilaria Platè: None declared, Eugenio Arrigoni: None declared, Fabio Mascella: None declared, Maria Cristina Focherini: None declared, Alessandra Bezzi: None declared, Palma Scolieri: None declared, Vincenzo Bruzzese: None declared, Viviana Ravagnani: None declared, Guido Rovera: None declared, Alessia Fiorenza: None declared, Rosetta Vitetta: None declared, Alarico Ariani Amgen, Janssen.

Background:Since 2022 clinicians have been consistently aware by the European Medical Agency (EMA) of prescribing Jak-inhibitors (JAKi) after assessing a risk/benefit ratio, especially in patients with rheumatoid arthritis (RA)1. Nevertheless, during the last years, uptake of selective JAKis has consistently increased, although limited data regarding differences between selective and unselective JAKis are available to date.Objectives:To assess differences between selective and unselective JAKIs in terms of discontinuation’s rate.Methods:In this retrospective study, all patients with RA treated with JAKis were prospectively enrolled from 22 Italian centres since 2017. Selective JAKi included filgotinib and upadactinib, whereas unselective JAKIs included tofacitinib and baricitinib. Reasons of discontinuation rates were: primary and secondary inefficacy, remission, adverse events [deaths, infections, onset of major cardiovascular events-(MACEs)-, deep vein thrombosis-(DVT)-, pulmonary embolism-PE, cancers].The following variables were collected at JAKi’s first prescription: sex, age, disease duration (years), smoking, BMI, comorbidities (diabetes, hypertension, dyslipidaemia, cancer, major cardiovascular events-MACEs), positive RF/ACPA, associated cDMARDs, prednisone and prednisone dosage (mg/day), previous use of JAKi, time to discontinuation (days), reasons of discontinuation, discontinuation rates for each JAKi, line of treatment, DAS28-ESR, b/tsDMARDS naïve patients.Results:693 patients were included in study. 395 (57%) patients received baricitinib, 150 (21.7%) tofacitinib, 94 (13.6%) upadacitinib and 54 (7.8%) filgotinib. The majority of patients were treated with unselective JAKi (78.6% vs 21.4% of selective JAKi). 157 (22.7%) patients discontinued JAKI after a median time of 334 days (IQR 152-869). Details of discontinuation rates for each drug are reported in Table 1.Reasons of discontinuation were primary inefficacy (n=55, 7.9%), secondary inefficacy (n=29, 4.2%), infections (n=9, 1.3%), PE/DVT (n=6, 0.9%), cancer (n=6, 0.9%), deaths (n=2, 0.3%), and other causes (n=7, 3.5%) including remission status in 1 patient. No MACEs were observed in this cohort during the follow up period, although 348 patients (50.2%) had at least one comorbidity at baseline. Notably, both VZV infection (n=3) and DVT/PE (N=6) occurred in patients on treatment with baricitinib.Among 157 patients who discontinued JAKi, a statistical difference between selective and unselective JAKIs was found (15.9% on selective JAKi vs. 84.1% on unselective JAKI, p value <0.001 at log-rank test, Figure 1). Finally selective JAKi were withdrawn before unselective JAKi (median 173 days, IQR 129-22 vs median 401.5 days, IQR 173.5-981).Conclusion:In this real-world cohort, only a minority of patients discontinued JAKi (22.7%). Primary and secondary inefficacy were the most common reasons of JAKi’s withdrawal. All TVP/PE and VZV infections occurred in the baricitinib group, probably due to different overall time of drug’s exposition. Finally, selective JAKis were discontinued earlier than unselective JAKi.REFERENCES:[1] Smolen JS, et al. Ann Rheum Dis 2023.Acknowledgements:NIL.Disclosure of Interests:Maddalena Larosa UCB, ABBVIE, AMGEN, Dario Camellino AStrazeneca, Boerhinger Ingelheim GSK, and Janssen, Andrea Becciolini: None declared, Eleonora Di Donato: None declared, Giuditta Adorni: None declared, Gianluca Lucchini: None declared, Daniele Santilli: None declared, Eugenio Arrigoni: None declared, Elena Bravi: None declared, Ilaria Platè: None declared, Alessandra Bezzi: None declared, Alessandra Bezzi: None declared, Maria Cristina Focherini: None declared, Fabio Mascella: None declared, Vincenzo Bruzzese: None declared, Palma Scolieri: None declared, Simone Parisi: None declared, Maria Chiara Ditto: None declared, Enrico Fusaro: None declared, Viviana Ravagnani: None declared, Guido Rovera: None declared, Alessia Fiorenza: None declared, Rosetta Vitetta: None declared, Antonio Marchetta: None declared, Alessandro Volpe: None declared, BERND RAFFEINER: None declared, Eleonora Celletti: None declared, Myriam Di Penta: None declared, Emanuela Sabatini: None declared, Francesco Cipollone: None declared, Francesca Ometto: None declared, Cecilia Giampietro: None declared, Valeria Nucera: None declared, Aurora Ianniello: None declared, Francesca Serale: None declared, Marta Priora: None declared, Dilia Giuggioli: None declared, Carlo Salvarani: None declared, Gilda Sandri: None declared, Federica Lumetti: None declared, FRANCESCO MOLICA COLELLA: None declared, Veronica Franchina: None declared, Aldo Molica Colella: None declared, Patrizia Del Medico: None declared, Rosalba Caccavale: None declared, Marino Paroli: None declared, Giulio Ferrero: None declared, Natalia Mansueto: None declared, Romina Andracco: None declared, Matteo Colina: None declared, Simone Bernardi: None declared, Francesco Girelli: None declared, Antonella Farina: None declared, Roberta Foti: None declared, Francesco De Lucia: None declared, Giorgio Amato: None declared, Rosario Foti: None declared, Alberto Lo Gullo: None declared, Mirco Magnani: None declared, Olga Addimanda: None declared, Massimo Reta: None declared, Alarico Ariani AMGEN, JANSSEN.

This work presents a generalized structure generation methodology for amorphous polymers by a simulated polymerization technique and 21-step molecular dynamics equilibration, which is particularly effective for high-Tg polymers. The essential framework and parameters of the techniques and algorithms are described in detail, and example input scripts are provided for use with the freely available Polymatic simulated polymerization code and LAMMPS molecular dynamics package. The capabilities of the methods are examined through application to six linear, glassy polymers ranging in functionality, polarity, and rigidity. Validation of the methodology is provided by comparison of the simulations and experiments for a variety of structural, adsorption, and thermal properties, all of which showed excellent agreement with available experimental data.

The promise of ultrapermeable polymers, such as poly(trimethylsilylpropyne) (PTMSP), for reducing the size and increasing the efficiency of membranes for gas separations remains unfulfilled due to their poor selectivity. We report an ultrapermeable polymer of intrinsic microporosity (PIM-TMN-Trip) that is substantially more selective than PTMSP. From molecular simulations and experimental measurement we find that the inefficient packing of the two-dimensional (2D) chains of PIM-TMN-Trip generates a high concentration of both small (<0.7 nm) and large (0.7–1.0 nm) micropores, the former enhancing selectivity and the latter permeability. Gas permeability data for PIM-TMN-Trip surpass the 2008 Robeson upper bounds for O 2 /N 2 , H 2 /N 2 , CO 2 /N 2 , H 2 /CH 4 and CO 2 /CH 4 , with the potential for biogas purification and carbon capture demonstrated for relevant gas mixtures. Comparisons between PIM-TMN-Trip and structurally similar polymers with three-dimensional (3D) contorted chains confirm that its additional intrinsic microporosity is generated from the awkward packing of its 2D polymer chains in a 3D amorphous solid. This strategy of shape-directed packing of chains of microporous polymers may be applied to other rigid polymers for gas separations. Polymer membranes were formed from the inefficient packing of 2D polymer chains in a 3D amorphous solid, forming small and large micropores that enable high gas selectivity and permeability. This strategy may be applied to other polymers.

BackgroundRecently, the new class of drugs, namely targeted synthetic (ts) DMARDs, has broadened the possibilities of treating rheumatoid arthritis (RA). In particular, Janus Kinase inhibitors (JAKi) are used in RA and are currently represented by four drugs: baricitinib, tofacitinib, upadacitinib and filgotinib. One of the first to be used in Italy was baricitinib, a JAKi acting on JAK1 and JAK2.ObjectivesThe aim of this study was to evaluate the clinical efficacy of baricitinib in a real-life setting in a cohort of RA patients.MethodsThis multicenter retrospective observational study included patients from 25 rheumatology centers diagnosed with RA and treated with baricitinib. The following were recorded for each patient: gender; age; duration of disease; presence of rheumatoid factor and anti-citrulline antibodies; concomitant treatment with conventional synthetic (cs) DMARDs; previous treatments with biological (b) or ts DMARDs. In order to evaluate the clinical efficacy, the retention rate was evaluated, calculated by means of the Kaplan-Meier method. The variables under examination were reported as frequencies and median with relative interquartile range.ResultsWe included 478 patients of which 380 (79.5%) were female. 286 (60.1%) patients tested positive for rheumatoid factor (RF) and 264 (55,2%) for anti-citrulline antibody (ACPA). The parameters analyzed are shown in Table 1. 105 (22.0%) patients were treated with baricitnib as first line (after csDMARD), the remaining patients had failed at least one bDMARD and 9 (1.9%) also failed a tsDMARD. In 34,7% of cases baricitinib was used as monotherapy, the most frequently used csDMARD was methotrexate (29.2%). The median period of therapy was 674 days (298-1087).The survival rate at 6 months was 94.6%, at 12 months it was 87,9%, at 24 months was 81.7% and at 48 months was 53.4% (Figure 1).The main causes that led to the discontinuation of baricitinib therapy were: primary ineffectiveness (7,3%), secondary ineffectiveness (4.2%) and adverse events (3,7% 5 TEP/DVT). The concomitant steroid therapy seems to be a negative prognostic factor (HR 1,65 95% CI 1.03-2.63; p=0.035) as well as the line of therapy (HR 1.35 95% CI 1.15-1.58; p=0.000).Table 1.CharacteristicsValueM:F98:380Age, median [IQR] yrs60 [51-70]Smokers, n (%) (**)YesFormerNo84 (18,8)76 (17,0)288 (64,2)Body Mass Index, median [IQR] kg/m^2 (*)24,8 [23,0-27,0]Disease Duration, median [IQR], months78 [32-163]RF positivity, n (%)286 (60,1)ACPA positivity, n (%)264 (55,2)SJC, median [IQR]5 [3-8]TJC, median [IQR]8 [4-12]ESR, median [IQR], mm/h33 [20-46]CRP, median [IQR], mg/dl1,3 [0,5-2,9]VAS Patient (0-100), median [IQR]70 [50-80]DAS28, median [IQR]5,4 [4,8-6,1]Line of treatment, [IQR]2 [2-3]Concomitant csDMARDs use, n (%)MTXLFNSSZHCQ140 (29,2)11 (2,3)3 (0,6)12 (2,5)Concomitant steroids use, n (%)237 (49,6)Steroids dose (PDN-Eq), median, mg/die5 [4-5]Prior bDMARDs use, n (%)TNFiIL6iIL1iCD20iCD80i164 (34,3)84 (17,6)08 (1,7)54 (11,3)Prior tsDMARDs use, n (%)Tofacitinib9 (1,9)Concomitant relevant disease, n (%)DiabetesHypercholesterolemiaMACEArterial HypertensionCancer36 (7,5)119 (24,9)28 (5,9)179 (37,4)24 (5,0)Figure 1.4 year retention rate of baricitinibConclusionThe efficacy of baricitinib in the treatment of RA in a real-life context appears consistent with what was reported by the pivotal studies. Furthermore, from this preliminary experience, seropositivity and combo therapy seems to not correlate with a better retention rate, while concomitant steroid therapy and line of treatment are a negative prognostic factor.References[1] Guidelli GM et al. Clin Exp Rheumatol. 2021 Jul-Aug;39(4):868-873.[2] Spinelli FR et al. Clin Exp Rheumatol. 2021 May-Jun;39(3):525-531.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundJanus kinase (JAK) inhibitors have been approved for the treatment of Rheumatoid Arthitis (RA) and other systemic or organ-specific autoimmune diseases. Sustained remission or low disease activity are target treatments recomended by European League Against Rheumatism (EULAR) in RA patients [1]. Upadacitinib (UPA), a reversible, oral JAK inhibitor, has been engineered to have a greater selectivity for JAK1 vs JAK2, JAK3, and tyrosine kinase. In the Phase 3 SELECT clinical trial program, UPA has been shown to be effective and well tollerate in patients with RA [2]. However, data on the use of UPA in real-world clinical practice are limited.ObjectivesTo evaluate UPA effectiveness in RA patients and to report the main reasons of suspension and the most relevant factor related to treatment persistence.MethodsIn 25 Italian rheumatological referral centers, all RA consecutive patients who received UPA were enrolled. Anamnestic data, treatment history and RA disease activity at baseline were recorded.The 6 and 12 months UPA retention rate was assessed with the Kaplan-Meier curve methods. The Cox analysis investigated the effect of age, sex, smoke habit, ACPA/RF presence, disease duration, DAS28-CRP, line of treatment, concomitant csDMARD treatment on UPA retention rate. A p-value < 0.05 was considered statistically significant.ResultsThe one-hundred-eleven enrolled patients median age 57 (IQR 50-65 yrs); M:F 28:83; disease duration 78 (IQR 40-170 months). The median observation period was 6.1 (IQR 3.2-10.2) months. The observation lasted 812 patients-months. The majority of patients (54.0%) were in mono-therapy and received steroids (respectively 54.0% and 58.6%) (Table 1).The UPA retention rate at 6, 12 months was, respectively 90.4% and 74.7% (Figure 1). The main discontinuation reason was lack of efficacy (42% of interruptions), cancer onset and infections (both 11%). No thromboembolic events were reported.According to the Cox analysis, no one of the above mentioned parameters were associated to high risk of treatment interruption.Table 1.Baseline characteristics UPACharacteristicsValueM:F28:83Age, median [IQR] yrs58 [50-65]Smokers, n (%) (**)YesFormerNo16 (16,5)17 (17,5)64 (66,0)Body Mass Index, median [IQR] kg/m^2 (*)24,7 [22,4-27,7]Disease Duration, median [IQR], months78 [40-170]RF positivity, n (%)72 (64,9)ACPA positivity, n (%)68 (61,3)SJC, median [IQR]4 [3-8]TJC, median [IQR]8 [5-11]ESR, median [IQR], mm/h32 [20-53]CRP, median [IQR], mg/dl1,2 [0,5-3,3]VAS Patient (0-100), median [IQR]70 [50-80]DAS28, median [IQR]5,5 [4,9-5,9]Line of treatment, [IQR]3 [2-4]Concomitant csDMARDs use, n (%)MTXLFNSSZHCQ41 (36,9)3 (2,7)1 (0,9)5 (4,5)Concomitant steroids use, n (%)65 (58,6)Steroids dose (PDN-Eq), median, mg/die5 [5-6]Prior bDMARDs use, n (%)TNFiIL6iIL1iCD20iCD80i53 (47,7)13 (11,7)02 (1,8)11 (9,9)Prior tsDMARDs use, n (%)BaricitinibTofacitinib9 (8,1)2 (1,8)Concomitant relevant disease, n (%)DiabetesHypercholesterolemiaMACEArterial HypertensionCancer12 (10,8)23 (20,7)5 (4,5)34 (30,6)4 (3,6)Figure 1.ConclusionUPA effectiveness appears to be confirmed. The safety profile of UPA 15 mg in real-world practice is consistent with data from Phase 3 SELECT trials, with no new safety signals.References[1]Smolen JS, et al. Ann Rheum Diseases 2023;82:3-18.[2]Burmester GR et al.Lancet 2018; 23;391(10139):2503-2512Acknowledgements:NIL.Disclosure of InterestsNone Declared.