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Introduction: High-flux hemodialysis membranes may modulate the cytokine storm of SARS-CoV-2, but their impact on chronic hemodialysis (CHD) patients is unknown. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers and clinical outcomes in CHD patients with SARS-CoV-2. Methods: A prospective, observational study on CHD patients with SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021. Pre- and postdialysis C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were determined at each session. Patients who underwent on-line hemodiafiltration (OLHDF) with a PMMA dialyzer were compared with those treated with OLHDF with a ATA dialyzer. The primary endpoint was the differences in the reduction ratio per session (RR) of CRP, PCT, IL-6, and IL-6 RR >25%. Results: We consecutively enrolled 74 CHD patients with COVID-19, 48 were treated with ATA membrane, and 26 with PMMA. Median IL-6 RR was higher in the ATA group compared to PMMA (17.08%, IQR −9.0 to 40.0 vs. 2.95%, IQR −34.63 to 27.32). Median CRP RR was 7.77% (IQR 2.47–13.77) in the ATA group versus 4.8% (IQR −2.65 to 11.38) in the PMMA group (p = 0.0017). Median PCT-RR% was 77.38% (IQR 70.92–82.97) in ATA group versus 54.59% (IQR 42.62–63.16) in the PMMA group (p < 0.0001). A multiple logistic regression analysis with IL-6 RR >25% as the outcome including the membrane employed, pre-dialysis IL-6, CRP, PCT, and ferritin showed that ATA led to a higher probability to reach the outcome (OR 1.891, 95% CI 1.273–2.840, p = 0.0018) while higher CRP favors the risk of lower IL-6 RR values (OR 0.910, 95% CI 0.868–0.949, p ≤ 0.0001). Conclusions: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile, regarding IL-6 RR, compared to PMMA.

Background/Aims Psoriatic arthritis (PsA) is a multi-system disease with a range of management options. Treatment may vary by geographic location. We compared disease characteristics and prescribing practices in the UK and Europe in the post-Covid era. Methods The ASSIST study was a cross-sectional observational study of PsA patients aged 18 years and older selected from 24 centres across 5 countries (UK, France, Germany, Italy and Spain) between July 2021 and March 2022 (IRAS: 287039). Patients attending a face-to-face appointment with a diagnosis of PsA made by a rheumatologist were selected by systematic sampling at each centre and treated in routine clinical practice. Patient and disease characteristics, current treatment and treatment decisions (medications unchanged, switched, added or reduced) were recorded. The analysis was descriptive, with no imputation of missing data. Results 503 patients were included, with arthritis subtype, patient age, disease activity and duration shown (Table 1). Physician- and patient-reported disease severity was highest in the UK, where median patient age was lowest. Conventional synthetic (cs) DMARDS constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), whereas biologic use was more frequent in Europe (68.1% vs 36.4%). Adalimumab was the most commonly used biologic in the UK and Spain. Adalimumab and secukinumab were equally used in Germany, and ixekizumab and adalimumab were joint-first in Italy. Implementing change to the current PsA treatment was most common in the UK, predominantly being a treatment increase. This may reflect the higher level of disease activity or younger patient age in the UK than other countries, as treatment escalation is more likely earlier in the disease course. In the UK, treatment escalation was more commonly achieved by medication addition (26.2%) than medication switch (14%) or dose increase (7.5%). In Europe, medication addition and switch were of more similar frequency (10.9% vs 9.85%). Conclusion Disease characteristics and treatment strategies varied between countries, but particularly between UK and the rest of Europe. In contrast to mainland Europe, csDMARDs predominated in the UK, perhaps reflecting current NICE guidelines. Treatment escalation was most common in the UK, in keeping with higher disease activity. Disclosure L. Watson: None. C. Coyle: None. M. Brooke: None. U. Kiltz: None. E. Lubrano: None. R. Queiro: None. D. Trigos: None. J. Brandt-Juergens: None. S. D'Angelo: None. A. Delle Sedie : None. E. Dernis: None. P. Helliwell: None. P. Ho: None. A. Hueber: None. B. Joven: None. M. Koehm: None. C. Montilla: None. J. Packham: None. J.P. Tasende: None. F.J.R. Garcia: None. A. Ruyssen-Witrand: None. R. Scrivo: None. S. Twigg: None. M. Welcker: None. M. Soubrier: None. T. Wirth: None. L. Gossec: Consultancies; AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB. Grants/research support; Amgen, Galapagos, Lilly, Pfizer, Sandoz, UCB. L.C. Coates: None.

Background/Aims A personalised approach is required to optimise management of psoriatic arthritis (PsA). Shared decision-making between physician and patient is key, resulting in greater patient satisfaction and outcomes. We assessed the degree of perceived collaboration following clinic visits in the UK and Europe and whether this was associated with treatment escalation. Methods The ASSIST study was a cross-sectional observational study of PsA patients aged 18 years and older selected from 24 centres across 5 countries (UK, France, Germany, Italy and Spain) between July 2021 and March 2022 (IRAS: 287039). Patients attending a face-to-face appointment with a diagnosis of PsA made by a rheumatologist were selected by systematic sampling at each centre and treated in routine clinical practice. Patients completed the collaboRATE questionnaire (scored 0-9), where high scores indicate greater perceived collaboration. The perceived efficacy in patient-physician interactions (PEPPI) tool (scored 5-25) assessed the patients’ view on their confidence in the consultation. Patient, physician, and disease characteristics were recorded, alongside treatment decisions (medications unchanged, switched, added or reduced). The analysis was descriptive, with no imputation of missing data. Results 503 patients were included, with key characteristics shown (Table 1). Generally, the level of disease severity was low (mean total PsAID score 3.6/10) and PEPPI scores were high, indicating patient confidence in the consultation. A subgroup (n = 10) perceived difficulty in sharing their concerns (PEPPI 5) had treatment escalation. However, in patients with high collaboRATE scores, even patients with low PsAID scores had treatment escalation. Conclusion Patients report high levels of shared decision-making in face-to-face PsA consultations, unrelated to treatment escalation. In patients with low PsAID scores, those with higher perceived collaboration are more likely to have treatment escalation than those without, perhaps reflecting the identification of otherwise undetected symptoms/concerns. Disclosure L.L. Watson: None. C. Coyle: None. M. Brooke: None. U. Kiltz: None. E. Lubrano: None. R. Queiro: None. D. Trigos: None. J. Brandt-Juergens: None. S. D'Angelo: None. A. Delle Sedie : None. E. Dernis: None. P. Helliwell: None. P. Ho: None. A. Hueber: None. B. Joven: None. M. Koehm: None. C. Montilla: None. J. Packham: None. J.P. Tasende: None. F.J.R. Garcia: None. A. Ruyssen-Witrand: None. R. Scrivo: None. S. Twigg: None. M. Welcker: None. M. Soubrier: None. T. Wirth: None. L. Gossec: Consultancies; AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB. Grants/research support; Amgen, Galapagos, Lilly, Pfizer, Sandoz, UCB. L.C. Coates: None.

Background/Aims Psoriatic arthritis (PsA) is a heterogeneous, multi-dimensional disease. Treatment pathways are not well defined and have to be tailored to the individual; however, little is known about the factors underpinning a decision to intensify treatment. By comparing treatment data between countries, we can understand more about factors influencing patient outcomes and establish international benchmarks in practice. Methods ASSIST was a cross sectional study of patients (18 years and older) diagnosed with PsA. Participants were selected from 24 centres across 5 countries (UK, France, Germany, Italy and Spain). Patients were selected from face to face (F2F) appointments using systematic sampling with random starting numbers generated for each site. Participants were treated as usual in their routine clinical practice. The Health Assessment Questionnaire (HAQ) and the EQ-5D-5L QoL survey were provided to all participants as patient-reported outcome tools. The perceived confidence on patient-physician interaction score (PEPPI) and the CollaboRATE measure were used to assess patient satisfaction with a consultation. Results 503 patients from 24 centres across five countries in Europe (49.1% F, 50.9% M) (mean age 53) participated in the survey between 12/07/2021-22/03/2022. Despite similar rates of treatment escalation and similar satisfaction with consultations, QoL was poorer in the UK. Comparing EQ-5D-5L scores, participants in the UK (107) reported worse outcomes across all domains except pain/discomfort versus participants in mainland Europe (396). 52.3% in the UK reported some problems with self-care versus 33.9% in mainland Europe. 72.9% of patients in the UK reported issues with mobility (mainland Europe: 61.6%). The UK had the highest percentage of participants reporting issues with anxiety (66.4%). The UK had the most severe HAQ scores, (mean= 0.936) compared to means of 0.62 or below in other countries. Physician-reported severity of disease was higher in the UK; however, patients in the UK reported the second highest PEPPI scores, the second highest collaboRATE scores and comparable methods of treatment escalation (dose adjustment or addition of another medication) to mainland Europe. Moreover, data on co-morbidities (including FCI categorical breakdown) does not demonstrate obvious variation between the UK and Europe. Conclusion Overall, patients with PsA in the UK reported lower quality of life (QoL) compared to patients in mainland Europe. It is not clear from our data why the UK performs less well on the majority of EQ-5D-5L domains and HAQ scoring compared to Europe. This may relate to variation in disease activity; however, there is potential selection bias in the higher disease activity reported by physicians in the UK as patients with more severe disease could have been selected for F2F appointments compared to mainland Europe. There may also be additional factors outside of the consultation impacting these scores, which could be identified with future research. Disclosure C. Coyle: None. L. Watson: None. M. Brooke: None. U. Kiltz: None. E. Lubrano: None. R. Queiro: None. D. Trigos: None. J. Brandt-Jürgens: None. S. D'Angelo: None. A. Delle Sedie: None. E. Dernis: None. P. Helliwell: None. P. Ho: None. A. Hueber: None. B. Joven Ibáñez: None. M. Köhm: None. C. Montilla Morales: None. J. Packham: None. J. Antonio Pinto Tasende: None. F. Ramíez García: None. A. Ruyssen-witrand: None. R. Scrivo: None. S. Twigg: None. M. Welcker: None. M. Soubrier: None. T. Wirth: None. L. Gossec: None. L. Coates: None.

Oliguric acute kidney injury due to traumatic rhabdomyolysis can be potentially lethal if the proper medical therapy combined with extracorporeal detoxification is not performed. Different extracorporeal techniques are available to overcome this syndrome. Here, we report the first case of removal of myoglobin and successful recovery from acute kidney injury in an elderly septic patient using supra-hemodiafiltration with endogenous reinfusion technique (HFR-Supra) combined with the medical therapy.

Chronic hemodialysis patients are at high risk of severe COVID-19 disease and death related to the infection. Anti-spike monoclonal antibodies administration reduces risk of disease progression and hospitalization in high-risk subjects but no clear data on end-stage renal disease are available. We report 2 cases of Bamlanivimab/Etesevimab administration to two not hospitalized chronic hemodialysis patients with SARS-CoV2 infection. Since they are large molecules (human immunoglobulin G1) with molecular weight of 146,000 Da, administration was conducted during the second hour of the dialysis session with no adverse reaction. Conclusions: Intradialytic administration of Bamlanivimab/Etesevimab could be considered safe and may allow adequate clinical observation time without hospital-stay prolongation.

Background/Aim: Supra hemodiafiltration with reinfusion of the endogenous ultrafiltrate (Supra-HFR) is a dialysis technique used to improve uremic toxin removal in the range of the middle molecular weight molecules. Supra-HFR does not require the preparation and online infusion of high-purity dialysis water because it allows the production of an endogenous ultrafiltrate that undergoes detoxification through an adsorbing resin. Patients and Methods: We investigated the ability of Supra-HFR to remove fibroblast growth factor 23 (FGF23), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and transforming growth factor alpha (TGF-alpha) after a single session dialysis in nine patients affected by end stage renal disease (ESRD). The same patients underwent a single session of online hemodiafiltration (OL-HDF) to evaluate possible differences in FGF23 and IL-6 levels. Results: A significant reduction in FGF23 was observed with both Supra-HFR (p=0.001) and OL-HDF. As for TNF-alpha and TGF-alpha, which were measured using Supra-HFR only, their percentage values were significantly lower at the end of dialysis than at the start (p=0.0028 and p=0.03, respectively). This did not change with post-dialysis rebound. Supra-HFR was found to have no effect on IL-6 and IL-8. Interestingly, the removal rate for FGF23 and IL-6 was similar to that observed with OL-HDF. Conclusion: Supra-HFR was not superior to OL-HDF, with suboptimal convective volume in the removal of the molecules tested, especially FGF23, which is considered a large middle molecular weight uremic toxin.

Background EUS-guided biliary drainage (EUS-BD) with Lumen Apposing Metal Stent (LAMS) is a mini-invasive approach for jaundice palliation in distal malignant biliary obstruction (D-MBO) not amenable to ERCP, with good efficacy and not exiguous adverse events. Aims and methods From January 2015 to December 2019, we retrospectively enrolled all the EUS-BD with electrocautery-enhanced LAMS for biliary decompression in unresectable D-MBO and failed ERCP. Primary study aims were to evaluate technical/clinical success and AEs rate. In case of maldeployment, we estimated the efficacy of an intra-operative rescue therapy. Secondary aims were to assess the jaundice recurrence and gastric outlet obstruction symptoms. Results Thirty-six EUS-BD were enrolled over a cohort of 738 patients (ERCP cannulation failure rate was 2.6%): 31 choledocho-duodenostomy and 5 cholecystogastrostomy. A pre-loaded guidewire through the LAMS was systematically used in case of common bile duct ≤ 15 mm or scope instability for a safe/preventive biliary entryway in case of intra-procedural complications. Technical success was 80.6% (29/36 patients). Seven cases of LAMS maldeployment during EUS-guided choledocho-duodenostomy were successfully treated with RT by an over-the-wire fully-covered Self-Expandable Metal Stent (FC-SEMS). The FC-SEMS was released through the novel fistula tract in endoscopic fashion in 5/7 cases and transpapillary in percutaneous-transhepatic-endoscopic rendezvous (1/7) and laparoscopic-endoscopic rendezvous (1/7) in the two remaining cases. The total efficacy of rescue therapy was 100%. Same-session duodenal SEMS was placed in 17 patients with optimal gastric outlet obstruction management. Final clinical success was 100% and no other late adverse events or FC-SEMS migration were observed. Conclusion EUS-BD with LAMS is effective for jaundice palliation after ERCP failure but with considerable adverse events. Maldeployment remains a serious complication with fatal evolution if not correctly recognized/managed. Rescue therapy must be promptly applied especially in tertiary-care centers with highly skilled endoscopists, interventional radiologist and dedicated surgeon.

Age-related hearing loss (presbycusis) is a chronic health condition that affects one-third of the world population. One hallmark of presbycusis is a difficulty hearing in noisy environments. Presbycusis can be separated into two components: alterations of peripheral mechanotransduction of sound in the cochlea and central alterations of auditory processing areas of the brain. Although the effects of the aging cochlea in hearing loss have been well studied, the role of the aging brain in hearing loss is less well understood. Therefore, to examine how age-related central processing changes affect hearing in noisy environments, we used a mouse model (Thy1-GCaMP6s X CBA) that has excellent peripheral hearing in old age. We usedin vivotwo-photon Ca2+imaging to measure the responses of neuronal populations in auditory cortex (ACtx) of adult (2–6 months, nine male, six female, 4180 neurons) and aging mice (15–17 months, six male, three female, 1055 neurons) while listening to tones in noisy backgrounds. We found that ACtx neurons in aging mice showed larger responses to tones and have less suppressed responses consistent with reduced inhibition. Aging neurons also showed less sensitivity to temporal changes. Population analysis showed that neurons in aging mice showed higher pairwise activity correlations and showed a reduced diversity in responses to sound stimuli. Using neural decoding techniques, we show a loss of information in neuronal populations in the aging brain. Thus, aging not only affects the responses of single neurons but also affects how these neurons jointly represent stimuli.SIGNIFICANCE STATEMENTAging results in hearing deficits particularly under challenging listening conditions. We show that auditory cortex contains distinct subpopulations of excitatory neurons that preferentially encode different stimulus features and that aging selectively reduces certain subpopulations. We also show that aging increases correlated activity between neurons and thereby reduces the response diversity in auditory cortex. The loss of population response diversity leads to a decrease of stimulus information and deficits in sound encoding, especially in noisy backgrounds. Future work determining the identities of circuits affected by aging could provide new targets for therapeutic strategies.

To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA).QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables.413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-axSpA). Nr-axSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-axSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS.We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-axSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.

Objectives To explore patient-defined flares in psoriatic arthritis (PsA), compared to an increase in disease activity in psoriatic arthritis (DAPSA) and to analyze the validity of a patient-reported flare question. Methods ReFlap (NCT03119805) was a longitudinal study in 14 countries of consecutive patients with definite PsA. Patients were seen twice in the context of usual care, 4.5 ± 2.2 months apart. Flares were reported by patients and physicians at the second visit using a single question. DAPSA worsening was defined as a change to a higher DAPSA category. Agreement between the definitions of worsening was calculated by prevalence adjusted bias adjusted kappa (PABAK). Validity of patient-reported flare was assessed by comparing patients with versus without flare and transition to flares. Results In 222 patients, mean disease duration 10.8 ± 8.3 years, 127 (58.8%) males: disease activity was low (mean DAPSA 11.5 ± 14.0); 63.3% received a bDMARD. Patient-reported flares between the 2 visits were seen in 27% patients (for these patients, mean 2.2 ± 3.7 flares per patient, mean duration 12.6 ± 21.0 days per flare). Physician- reported flares were seen in 17.6% and worsening in DAPSA in 40.1% of patients. Agreement between definitions was moderate (PABAK = 0.32-0.59). Patients in flare had significantly more active disease than patients not in flare for all outcomes (all P < 0.001). At the patient-level, transition to flare state was associated to a worsening in disease activity and impact outcomes. Conclusions Patient flares were frequent and were associated with active and symptomatic disease. These findings provide preliminary validation for patient-reported flares in PsA.

BACKGROUND AND AIMS Arteriovenous fistula (AVF) must be the first choice where eligible and a prompt approach within 48–72 h should be performed in case of acute AVF failure in order to maintain the patency of the vascular access. Evaluation of the most appropriate de-clotting technique must be made considering the patient's comorbidity, AVF characteristics and absolute, relative and temporary contraindications to each kind of corrective intervention. The outcome is different between the multiple methods and nowadays mechanical thromboaspiration (MT) seems to be an innovative and promising approach. METHOD A total of 9 AVF of 9 chronic haemodialysis patients with acute AVF failure were treated with MT between January 2019 and January 2022 and were retrospectively evaluated. MT was carried out via Indigo catheter (Penumbra Inc.), an aspiration system intended for the removal of emboli and thrombi from vessels through venipuncture of AVF/AVG: the continuous aspiration helps distinguish clots from normal blood flow; in case of resistant clots, separators of many sizes can be used at the tip of the catheter to facilitate their fragmentation and aspiration. Adjunctive procedures such as balloon angioplasty (used at all sites), local fibrinolysis, heparin infusion, or stents placement were considered. Technical success was defined by clot removal from AVF or AVG. Clinical success was defined by the restoration of thrill and bruit together with AVF usability after the procedure. Vascular access survival defined as AVF/AVG usability at 3 and 6 months was assessed. RESULTS Average age was 71.2 years; dialysis vintage was 93.4 months. Medium follow-up was 13.1 months. All patients needed placement of a temporary central venous catheter (CVC) and dialysis before the MT. Technical success was achieved in 100% of the procedures, clinical success was achieved in 88.9% of the MT (despite the technical success, in 1/9 patients AVF could not be used due to a severe residual venous stenosis). None reported peri-/intraprocedural complications. In 2/9 MT there was no use of anticoagulation; in 5/9 patients, a single unfractionated heparin bolus was used (2500 UI) during the manoeuvre; in 2/9 patients, a single 2500 UI bolus plus continuous intravenous infusion of unfractionated heparin was administered combined with local thrombolysis with urokinase: both patients needed blood transfusions after the manoeuvre, one of them reporting severe haemorrhage from AVF. As adjunctive procedures, 9/9 patients underwent balloon angioplasty; one of them needed stent placement over the venous stenosis. CVC was removed less than 48 h from the procedure in 5/9 patients (55.6%), in 3/9 patients it was removed after 48 h, while 1/9 patients maintained the temporary vascular access due to the lack of clinical success after MT. Double-needle puncture occurred after a medium time of 3.5 days. AVF survival at 3 months and 6 months was 66.6% (6/9 patients), while 3/9 patients faced AVF failure (1/3 patients deceased 2 months after the procedure with a functioning AVF, in 1/3 patients a relapse of AVG thrombosis occurred 2 months after the procedure, 1/3 never reached clinical success due to severe residual venous stenosis). At the time of study design, 3/9 patients resulted to be deceased due to causes unrelated to the procedure. (1/3 due to complications of abdominal surgery, 1/3 due to sepsis, 1/3 due to subarachnoid haemorrhage). CONCLUSION MT is an innovative yet functional and safe procedure that allows declotting of the thrombosed AVF while reducing or avoiding anticoagulation and/or surgery.

BACKGROUND AND AIMS High flux haemodialysis membranes may modulate the cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their impact in chronic haemodialysis (CHD) patients is not assessed [1, 2]. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers in CHD patients with SARS-CoV-2. METHOD A prospective, observational study on CHD patients (age ≥18 years) affected by SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021 and dialysis was performed at S. Orsola University Hospital (Bologna, Italy) Dialysis Unit. Mechanical ventilation at diagnosis was exclusion criteria. Pre- and post-dialysis C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were determined at each session and corrected for haemoconcentration during the complete SARS-CoV-2 period. Patients who underwent online haemodiafiltration (OLHDF) with PMMA dialyzer (Filtryzer BG-U™, Toray, surface area 2.1 m2 cut-off 20 kDa, KUF 43 mL/h/mmHg) were compared with those who underwent OLHDF with ATA dialyzer (SolaceaTM Nipro, surface area 2.1 m2 cut-off 45 kDa, KUF 72 mL/h/mmHg). The primary endpoint was to assess the differences in the reduction ratio/session (RR) of CRP, PCT and IL-6. RESULTS A total of 74 patients were enrolled, 48 were treated with ATA and 26 were with PMMA (420 versus 191 dialysis sessions). The main results are shown in Table 1. Median IL-6RR% was higher for ATA [17.08%, interquartile range (IQR) −9.0 to 40.0 versus 2.95%, IQR −34.63 to 27.32]. CRP and PCT showed higher RR with ATA in comparison to PMMA. When IL-6RR > 25% was the dependent variable in the multiple logistic regression analysis only ATA showed a significant correlation [odds ratio (OR) 1.891, 95% confidence interval (95% CI) 1.273–2.840, P = .0018) while higher CRP favoured the risk of lower IL6RR (OR 0.9101, 95% CI 0.868–0.949, P CONCLUSION In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile than PMMA, in particular regarding IL-6 RR.

BACKGROUND AND AIMS The QTc interval is a marker of arrhythmic risk in dialysis patients, and its lengthening has been associated with an increased risk of sudden death [1]. This phenomenon could be due to the accumulation of uremic toxins and their rapid removal with dialysis causing an imbalance of electrolytes currents [2]. The aim of the study is to describe the kinetics of potassium (K+) and other electrolytes during and after dialysis with the goal of validate a mathematical model for predicting the respective kinetics [3]. The secondary endpoint is to identify a correlation between the kinetics of intra (Ki) and extracellular K+ (Ke) during and after dialysis and the QTc interval. METHOD A total of 6 anuric HD patients were enrolled in an interventional, exploratory, prospective study. Clinical and pharmacological factors favouring the onset of arrhythmias or influencing the total mass of K + were excluded. Ki and Ke, Ca2+ Na, blood gas analysis, glucose and urea every 30 min were assessed during a 4 h HFR Supra dialysis session, the subsequent 7 h and at the start of the following session after 48 h. A 12-lead ECG was performed with the same schedule, and a bioimpedance vector analysis (BIVA) was obtained at the start and the end of the dialysis and 1 and 7 h after dialysis. Dialysate electrolytes were Na 140 mEq/L, K 3 mEq/L, Ca2+ 1.5 mEq/L and HCO3– 30 mmol/L. A selective ion probe was used to measure K+; the Ki value was obtained by an indirect formula expressed in a previous study [4]. The model of K + kinetics includes the Na+/K+/ATPase-dependent pump, the passive diffusion of K + from the intracellular to the extracellular compartment, the diffusion of K + through the filter, the intradialytic volume variation, the K + and solute rebound after dialysis, and the role of plasma osmolality [3]. RESULTS The model showed a better correlation to the in vivo data during the HFR phase than the post-dialytic one regarding Ke, sodium, HCO3– and Ca2+. The wide variability recorded by Ki is significantly in contrast with the stability predicted by the model, and the entity of post-dialysis Ca2+ drop was greater than that predicted by the model. Kinetics prediction of urea had a precise fitting with in vivo data in every phase. In Table 1, the in vivo results of the 6 patients regarding Ke, Ki, Ki/Ke, Ca2+ and QTc during and after HFR are resumed. In Fig. 1, we see the data extrapolated from a patient (likewise the others), where the greatest waving of the QTc occurred in the first hour post HFR in parallel with fluctuations of Ki and Ki/Ke. CONCLUSION The mathematical model for the prediction of the kinetics of solutes has shown a good correspondence with the in vivo data of K+, sodium, urea, Ca2+ and HCO3– during HFR, although it still needs to be refined in the post-dialysis phase. The major discrepancies for Ki could be due to difficult analytical processing. As to the greater drop of Ca2+ compared with the predicted, it can be due to the role played by other Ca2+ compartments in addition to the intra and extracellular ones. Although during the intradialytic period we faced a shortening of the QTc interval with a significant reduction in Ke, greater Ki/Ke and an increase in Ca2+ the post-HFR period appeared to be the most critical period. This phase corresponded to the largest fluctuations in QTc values, Ki, Ki/Ke ratio, and to the rapid rebound of K + and the drop of Ca2+.

OBJECTIVE Sleep quality is diminished in patients with psoriatic arthritis (PsA) and close to 40% of PsA patients consider sleep difficulties a priority domain. This work analyzes determinants of impaired sleep in patients with PsA. METHODS This was a cross-sectional analysis of an observational study (ReFlap, NCT NCT03119805), which included adult patients with definite PsA with≥2 years disease duration from 14 countries. Sleep was assessed using the patient self-reported evaluation of sleep on a 0-10 numerical scale, included in the Psoriatic Arthritis Impact of Disease questionnaire (PSAID-12). A score≥4 was considered as sleep impairment. Demographic and clinical variables associated to sleep impairment were assessed through univariate analysis and Poisson regression modeling leading to prevalence ratio (PR) [95% confidence interval]. RESULTS A total of 396 patients were analyzed: mean age 51.9±12.6 years, 51% were females, 59.7% were receiving biologic therapy, 53.3% had 1-5% of body surface area affected by psoriasis; 23.7% were in remission and 36.9% in low disease activity according to the Disease Activity in Psoriatic Arthritis (DAPSA) score. Median (25th-75th) patient's self-evaluation of sleep difficulties was 2 (0-6), 157 (39.6%) had sleep impairment. In the Poisson regression model, self-reported levels of anxiety (PR: 1.05 [1.02-1.08], P=0.003) and pain (PR: 1.06 [1.04-1.09], P

The term autophagy encompasses different pathways that route cytoplasmic material to lysosomes for degradation and includes macroautophagy, chaperone-mediated autophagy, and microautophagy. Since these pathways are crucial for degradation of aggregate-prone proteins and dysfunctional organelles such as mitochondria, they help to maintain cellular homeostasis. As post-mitotic neurons cannot dilute unwanted protein and organelle accumulation by cell division, the nervous system is particularly dependent on autophagic pathways. This dependence may be a vulnerability as people age and these processes become less effective in the brain. Here, we will review how the different autophagic pathways may protect against neurodegeneration, giving examples of both polygenic and monogenic diseases. We have considered how autophagy may have roles in normal CNS functions and the relationships between these degradative pathways and different types of programmed cell death. Finally, we will provide an overview of recently described strategies for upregulating autophagic pathways for therapeutic purposes.

Objective: To report a case of gastric epithelioid haemangioendothelioma, given its low incidence. Introduction: Epithelioid haemangioendothelioma is a vascular neoplasm composed of epithelioid or histiocytoid cells with endothelial characteristics. They have a very low incidence of approximately one per one million and are usually asymptomatic with a difficult preoperative diagnosis. Case Report: This study reports the case of a 58-year-old woman with a history of chronic anaemia. She underwent an elective upper endoscopy with evidence of an ulcerated submucosal lesion in the gastric antrum. The histological examination performed over the endoscopic biopsies showed the vascular characteristic of the tumor and endosonography confirmed the submucosal origin of the lesion. After resective surgery, the tumor showed the histological and immunohistochemical features of the epithelioid haemangioendothelioma. Conclusion: Surgery in the form of wide excision seems to be the treatment of choice for this rare neoplasm in the absence of histological markers of malignant potential.

The use of biosimilars is constantly growing, prompting healthcare payers to encourage the switch to these drugs which are less expensive than the reference bio-originator. While switching from a bio-originator to a biosimilar is supported by increasing evidence, data on the switch between different biosimilars of the same reference product are scant. Our study aimed to evaluate the effectiveness of the non-medical switch both between adalimumab (ADA) bio-originator and SB5 biosimilar and between two different ADA biosimilars in patients with inflammatory chronic arthritis.We observed adult patients with a diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) treated with ADA bio-originator or ABP501 ADA biosimilar (Amgevita) who switched to SB5 ADA biosimilar (Imraldi) for administrative/economic reasons. Patients were followed up for 4 months.One hundred and ten patients [33 RA, 40 PsA, 37 axSpA; F:M= 49:61; median age 56 years (25th-75th percentile 48-66)] switched from ADA bio-originator to SB5. After 4 months (T4), we observed a significant reduction of patients in remission/low disease activity (baseline 92.7% vs. T4 80.9%; p=0.009), with a risk of moderate-high disease activity significantly higher after the switch [RR 2.6 (95% IC 1.2 to 5.7), p=0.01]. However, no differences were found in DAS28-CRP, DAPSA, ASDAS-CRP, and BASDAI, while patients with RA and PsA experienced a worsening in the patient global assessment-VAS (p=0.04 and p=0.02, respectively), and in patients with PsA a worsening in HAQ was also observed (p=0.03). Forty patients switched from ABP501 biosimilar to SB5 [12 with RA, 25 with PsA, and 3 with axSpA; F:M=24:16; median age 56 years (25th-75th percentile 44-66)]. After 4 months, no differences in DAS28-CRP and DAPSA nor in the percentage of patients in remission/low disease activity were found compared to baseline. Likewise, no differences were found in patient-reported outcomes (PROs).Our results provide a reassuring profile of effectiveness when switching from ADA originator to one of its biosimilars and between two different biosimilars. However, the worse outcome in PROs in patients initially treated with the bio-originator addresses the attention to a possible nocebo response, which should encourage comprehensive communication with patients.

Psoriatic arthritis (PsA) is a chronic inflammatory condition characterized by psoriasis, synovitis, enthesitis, spondylitis, and the possible association with other extra-articular manifestations and comorbidities. It is a multifaceted and systemic disorder sustained by complex pathogenesis, combining aspects of autoinflammation and autoimmunity. Features of PsA autoinflammation include the role of biomechanical stress in the onset and/or exacerbation of the disease; the evidence of involvement of the innate immune response mediators in the skin, peripheral blood and synovial tissue; an equal gender distribution; the clinical course which may encounter periods of prolonged remission and overlapping features with autoinflammatory syndromes. Conversely, the role of autoimmunity is evoked by the association with class I major histocompatibility complex alleles, the polyarticular pattern of the disease which sometimes resembles rheumatoid arthritis and the presence of serum autoantibodies. Genetics also provide important insights into the pathogenesis of PsA, particularly related to class I HLA being associated with psoriasis and PsA. In this review, we provide a comprehensive review of the pathogenesis, genetics and clinical features of PsA that endorse the mixed nature of a disorder at the crossroads of autoinflammation and autoimmunity.

Description, TSC1/hamartin haploinsufficiency increases risk for tauopathy by promoting tau acetylation and accumulation., Age-associated neurodegenerative disorders demonstrating tau-laden intracellular inclusions are known as tauopathies. We previously linked a loss-of-function mutation in the TSC1 gene to tau accumulation and frontotemporal lobar degeneration. Now, we have identified genetic variants in TSC1 that decrease TSC1/hamartin levels and predispose to tauopathies such as Alzheimer’s disease and progressive supranuclear palsy. Cellular and murine models of TSC1 haploinsufficiency, as well as human brains carrying a TSC1 risk variant, accumulated tau protein that exhibited aberrant acetylation. This acetylation hindered tau degradation via chaperone-mediated autophagy, thereby leading to its accumulation. Aberrant tau acetylation in TSC1 haploinsufficiency resulted from the dysregulation of both p300 acetyltransferase and SIRT1 deacetylase. Pharmacological modulation of either enzyme restored tau levels. This study substantiates TSC1 as a novel tauopathy risk gene and includes TSC1 haploinsufficiency as a genetic model for tauopathies. In addition, these findings promote tau acetylation as a rational target for tauopathy therapeutics and diagnostic.

Age-associated neurodegenerative disorders demonstrating tau-laden intracellular inclusions are known as tauopathies. We previously linked a loss-of-function mutation in the TSC1 gene to tau accumulation and frontotemporal lobar degeneration. Now, we have identified genetic variants in TSC1 that decrease TSC1/hamartin levels and predispose to tauopathies such as Alzheimer’s disease and progressive supranuclear palsy. Cellular and murine models of TSC1 haploinsufficiency, as well as human brains carrying a TSC1 risk variant, accumulated tau protein that exhibited aberrant acetylation. This acetylation hindered tau degradation via chaperone-mediated autophagy, thereby leading to its accumulation. Aberrant tau acetylation in TSC1 haploinsufficiency resulted from the dysregulation of both p300 acetyltransferase and SIRT1 deacetylase. Pharmacological modulation of either enzyme restored tau levels. This study substantiates TSC1 as a novel tauopathy risk gene and includes TSC1 haploinsufficiency as a genetic model for tauopathies. In addition, these findings promote tau acetylation as a rational target for tauopathy therapeutics and diagnostic.

Background Patients with Crohn's disease have an increased aortic stiffness, a known cardiovascular risk factor. Anxiety, a key factor of the brain--gut axis in patients with Crohn's disease, is implicated in the pathogenesis and progression of the disease, and is linked with aortic stiffening in other clinical settings. Objectives Considering that depression is frequently linked to anxiety in Crohn's disease, we performed a mediation analysis to reveal the potential link between anxiety, depression and aortic stiffness in these patients. Methods Multicentre observational cross-sectional study of 86 consecutive patients with Crohn's disease and 86 matched control individuals. The connections between anxiety, depression, disease duration, aortic pulse wave velocity (aPWV), brachial and central SBP were tested using partial least squares structural equations modelling. Results In patients with Crohn's disease, anxiety (path coefficient: 0.220, P = 0.01) and disease duration (path coefficient: 0.270, P = 0.02) were associated with aPWV that in turn was associated with brachial SBP (path coefficient: 0.184, P = 0.03). These associations were even stronger in patients with active disease. The connection between anxiety and aPWV was in part mediated by central SBP (indirect effect: 0.090, P = 0.01; indirect-to-total effect ratio: 41%) as well as, in a pilot substudy, by sympathetic hyperactivity. Anxiety and depression were highly correlated in patients with Crohn's disease. Consequently, results were confirmed when anxiety was substituted by depression. Conclusion The connections of anxiety, depression and chronic inflammation with aPWV and SBP could suggest the first evidence of a brain--gut--vascular axis and new potential targets for therapy in patients with Crohn's disease.

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Background: In hemodialysis patients, a tunneled-cuffed permanent catheter is mandatory when the arteriovenous fistula is not feasible. The major risks of the use of tunneled-cuffed permanent catheter are bloodstream infections. The aim of this study is to analyze bloodstream infections from tunneled-cuffed permanent catheter in hemodialysis patients. Methods: An observational prospective study was carried out and 79 hemodialysis patients with tunneled-cuffed permanent catheter were enrolled. Patients were divided into those with bloodstream infections from tunneled-cuffed permanent catheter and those without. Their clinical and laboratory characteristics were compared. An original tunneled-cuffed permanent catheter lock therapy sequence was carried out combined with systemic antibiotic therapy. In case of antibiotic resistance, the tunneled-cuffed permanent catheter was removed. Results: The patients affected by bloodstream infections from tunneled-cuffed permanent catheter were 16/79 (20.3%). The bloodstream infection from tunneled-cuffed permanent catheter’s incidence rate was 0.52 per 1000 catheter days. Twenty-three bloodstream infections from tunneled-cuffed permanent catheter were found in 16/79 patients who used tunneled-cuffed permanent catheter. Staphylococcus aureus was the cause of bloodstream infection from tunneled-cuffed permanent catheter in 35% of the cases and Staphylococcus epidermidis in 30% of the cases. Risk factors were infection located in other organs and the presence of peripheral obstructive arterial disease. Conclusion: The enrolled cohort showed a reduced bloodstream infection from tunneled-cuffed permanent catheter incidence rate in comparison with the reference value (1 per 1000 catheter days). To reduce the number of bloodstream infections from tunneled-cuffed permanent catheter, hand hygiene and asepsis management of the tunneled-cuffed permanent catheter during the connection to the extracorporeal circuit and an original tunneled-cuffed permanent catheter lock therapy sequence seem to be the most efficient measures. Infections of other organs and the presence of peripheral obstructive arterial disease are the most important risk factors for bloodstream infections from tunneled-cuffed permanent catheter.

Purpose: To assess the usefulness of a dedicated questionnaire for patients with inflammatory bowel diseases (IBD) treated with biological drugs for the detection of ocular extraintestinal manifestations (EIMs). IBD can cause extraintestinal symptoms including ocular complaints which are frequently ignored and may be associated with significant morbidity, including blindness. Methods: We developed a questionnaire, named Ocular Manifestations in IBD Screening (OMIS) questionnaire, after agreement between gastroenterologists and ophthalmologists. The questionnaire was administered by a non-ophthalmologist physician to 96 IBD patients treated with biological drugs. Results: 35 patients (36.5%) were selected for the ophthalmologic examination on the basis of a positive screening test. Ocular EIMs were detected in 29 of 35 patients (83%). Conclusion: A specific questionnaire can be useful for non-ophthalmologist physicians in a real world setting in order to select patients to be addressed to an ophthalmological visit, creating an integrated multidisciplinary clinical team, to improve management of IBD in order to prevent disability and guarantee quality of life.

Objectives: Women of childbearing age may be affected by psoriatic arthritis (PsA) and ankylosing spondylitis (AS). The aim was to assess the impact of biological agents (bDMARDs) on the fertility of women with PsA and AS by evaluating the serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and luteinising hormone (LH). Methods: Consecutive female patients (18-45 years) affected by PsA or AS starting a bDMARD were retrospectively evaluated at baseline (T0) and after 8 months (T8) of treatment. At both visits, demographic and clinical data were obtained. AMH, LH, and FSH serum levels were measured. A population of fertile women matched for age, body mass index and smoking habit was included as healthy controls (HCs). Results: Twenty-four patients with PsA, 20 with AS, and 44 HCs were included. The median (25th-75th percentile) levels of AMH in patients were 0.74 ng/ml (0.29-2) at baseline and 0.71 ng/ml (0.19-1.9) (p=n.s.) at T8. The median levels of AMH in HCs were 1.56 ng/ml (0.37-2.90), with no difference compared to patients. No correlation was found between the serum AMH levels and the indexes of disease activity for both PsA and AS. No differences were found in the serum levels of FSH and LH before and after treatment with bDMARDs. Conclusions: Our results support the use of bDMARDs in female patients with SpA. AMH levels were not influenced by bDMARDs nor by disease activity. AMH could be useful to assess the quantitative aspect of ovarian reserve in female SpA patients.

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant.

BACKGROUND AND AIM There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naive to ADA and naive to anti-tumor necrosis factors; group B, naive to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P

Background and Aims Hyperoxaluria is a rare metabolic disorder chacterized by widespread calcium oxalate deposition, if plasmatic oxalate level (pOx) overcomes saturation threshold. It could be primary (PH), a recessive disease associated with mutation of the liver enzyme LDH, or secondary (SH), in 75% due to intestinal malabsorption. Urolithiasis could be the first complication, and renal involvement could progress until end-stage renal disease (ESRD). Mean pOx is higher in chronic dialysis patients than healthy individuals because of impaired renal clearance. Oxalate molecular weight (MW) is 88 Da and its clearance is that of low MW uremic toxins. Our aim is to assess an association between arteriovenous fistula (AVF) failures and Hyperoxaluria. Method In the period between 1/1/2004 and 12/31/2020, diagnosis of Hyperoxaluria was carried out in 6 patients out of 1530 chronic dialysis patients (0.39%). The median age of patients was 65.5 [26-72] years, the male/female ratio was 3:3 and the median dialysis vintage was 36 [1-181] months. Three patients come to nephrological referral at stage 5 of CKD while 1 patient came to Italy when chronic HD was already started. At that time pOx was not considered. In these 4 patients the presumptive diagnosis of ESRD was urolithiasis and diagnosis of Hyperoxaluria was carried out after the beginning of chronic dialysis, when pOx and genetic analysis were performed. In 1 case biopsy on the kidney graft and in 1 case kidney biopsy after nephrectomy were performed: oxalate deposition was detected. For 2/6 patients diagnosis was carried out after biopsy of native kidneys before starting dialysis. All patients started medical therapy for hyperoxaluria. Five out of 6 patients were eligible to HD, 1/6 to PD. AVF was judged the first choice vascular access. Results PH was diagnosed in 3/6 patients: mutations were detected on chromosome 2. Malabsorption secondary to short bowel syndrome and chronic pancreatitis could be assumed as causes of SH in 3 patients. Patient 1 underwent 2 combined liver-kidney transplantation: the first failed by arterial grafts thrombosis and the second by renal primary non-function but the liver was still functioning, he died on HD after 12 years. Patient 2 underwent liver and kidney transplantation and she is nowadays dialysis-free. The median pOx pre-dialysis and before diagnosis was 165 [98-259] umol/L (Table 1). Patients on chronic HD underwent median of 3 [2-5] AVF interventions. Nine AVFs were distal and 4 were proximal. The most frequent complication was AVF thrombosis despite ASA treatment: half of the cases showed secondary AVF non-function, the other half of AVFs failed to mature. Six tunneled cuffed permanent catheters (TCCs) as definitive vascular access were successfully placed in the 5 patients on chronic HD. Warfarin therapy was started to avoid TCCs thrombosis. The median survival of TCCs was 9.5 [3-48] months. All the patients had a history of deep venous thrombosis (DVT). Conclusion To our knowledge this is the first case series of multiple AVF failures in patients with hyperoxaluria. In our experience TCCs show longer survival then AVF in this group of patients, even if it could not be excluded the role of warfarin in favoring this result. Even though a link between hyperoxaluria and thrombosis is well established, the exact underlying mechanism is still uncleared. The role of PD as dialysis technique of “first choice” should be enhanced also when residual renal function is abolished. In ESRD patients with urolithiasis, diagnosis of Hyperoxaluria should be ruled out before AVF placement.

Background and Aims Several chronic medical conditions appear to increase the risk of severe COVID-19. Chronic kidney disease (CKD) patients have a high risk of symptomatic infection and severe respiratory symptoms because of chronic inflammation, uremic toxins accumulation, endothelial dysfunction and an impaired immune response. Even though the presence of one or more comorbidities increases the risk of mortality, information of the outcome of COVID-19 in CKD patients is not yet available. The aim of the study is to present the incidence and outcome of COVID-19 in patients referring to our Nephrology Unit considering CKD patients, dialysis patients and kidney transplant recipients. MO520 Table 1. Demographic, clinical and radiological features. Variables Total (n=52) Survivors (n=39) Nonsurvivors(n=13) Age, yr 67.2± 13.8 65± 14 72± 12 Woman 21 (39%) 17 (44.7%) 5 (13%) Comorbidity CV disease 41 (78.8%) 30 (79%) 11(84.6%) DM 22 (42%) 14 (36.8%) 8 (61.5%) Cancer 18 (31%) 12 (31.6%) 6(46.1%) BMI>30 7 (3%) 4(10.5%) 2(15.4%) Dialysis 31(59.5%) 24 (63.1) 6 (46%) Kidney transplantation 16 (30.7%) 11 (29%) 2 (15%) CKD IV-V stage 4 (7%) 2 (5.2%) 1 (7.7%) Onset of Symptoms fever 29 (79%) 22(58%) 7 (13%) cough 3(6%) 2 (5.2%) 1 (7.7%) dyspnea 8 (15.4%) 4 (10.5%) 4 (30.8%) Symptomless 8 (15.4%) 6 (15.8%) 2 (15.4%) Admission HRCT Bilateral peripheral ground-gass opacity 39(81.2%) 31 (79.5%) 8(88.8%) Unilateral opacity 6 (12.5%) 5(12.8%) 1 (11.1) No opacity 3 (6.2%) 3 (7.7%) 0 PaO2/FiO2 ratio 330 ± 102. 376 ±93 286 ±86 Method This study is prospective single centre carried out considering patients referring to the Nephrology Unit of St. Orsola University Hospital in Bologna with COVID 19 diagnosis from 15THMarch to 30THMay 2020. Results Our cohort included 52 patients admitted to our Nephrology Unit because of Sars Cov2 infection confirmed by positive reverse transcriptase polymerase chain reaction on nasopharyngeal swab. The mean age was 67.2 ± 13.8 years (range, 33-88 years). Demographic, clinical and radiological features in Table 1. Forty-eight patients (92.3%) underwent chest TC. The main findings were: several bilateral interstitial pneumonia (39 patients, 81.2%), monolateral peripheral ground-glass opacities (6 patients, 12.5%), no signs of pneumonia (3 patients, 6.2 %). Clinical course is highly variable: 18 patients (34.6 %) were asymptomatic, 23 patients (44 %) had a mild course requiring low flux oxygen therapy and 11 patients (21%) presented severe pneumonia and respiratory distress that requires ventilatory support in intensive care unit. Forty patients (70%) had hydroxychloroquine-azithromycin dual therapy, 3 patients (6%) had antiviral therapy in addiction. Sixteen patients (31%) with P/F

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome.

BackgroundPsoriatic arthritis (PsA) is a chronic, immune-mediated, inflammatory arthropathy, distinctively involving joints and enthesis. The improved understanding of PsA pathogenesis has enabled the development of biological disease-modifying anti-rheumatic drugs (bDMARDS) targeting specific cytokines and signalling pathways. The availability of these drugs deeply modified PsA history, by preventing disease progression and by improving quality of life. Nevertheless, bDMARDS are not effective in all the patients who may experience primary or secondary inefficacy or adverse events development.ObjectivesIn a real-life scenario, we evaluated the bDMARDs retention rate in a large PsA cohort. In detail, we compared drug survival of the first and second biological drug and we investigated the presence of factors associated with the bDMARDs treatment withdrawal.MethodsWe longitudinally evaluated adult PsA patients (2016 CASPAR criteria) treated with at least one bDMARD during disease history. For each PsA patient, the clinical and laboratory data, including demographics, past medical history with the date of diagnosis and treatments, clinical disease phenotypes, were collected in a standardized, computerized and electronically filled form. The retention rate was estimated by using the Kaplan-Meier method. Predictors for bDMARDs withdrawal were investigated in univariate and multivariate Cox proportional hazards analysis, adjusted for relevant variables.ResultsThe present analysis included 223 PsA patients [M/F 91/132; median age 57 years (IQR 17); median disease duration 120 months (IQR 132)]. Adalimumab and Etanercept were the most frequently prescribed bDMARDs (41.5% and 41.0%, respectively). The retention rate of the first prescribed bDMARD as reported in Figure 1A: in detail, we found a 12-months retention rate of 79.8%. The comparison between etanercept and adalimumab showed a similar 12-months retention rate, but significantly higher for etanercept at 24 months (82.4% versus 69.5%, p=0.0034, Figure 1B). Out of 223 enrolled PsA patients, 109 (48.9%) received only one bDMARDs, while the remaining 114 (51.1%) received at least 2 drugs. When comparing these two groups of patients, drug survival at 24 months was significantly higher in patients treated with one bDMARD in comparison with those treated with at least two drugs (67.7% versus 52.2%, p=0.03, Figure 1C). Finally, female sex and anxiety-depressive disorders were significantly associated with the treatment with at least two dDMARDs (p=0.005 and p=0.01, respectively).ConclusionThe results of the present study demonstrated a higher retention rate in the first-line bDMARDs treatment in comparison with second-line. Female sex and anxiety-depressive disorders may negatively affect drug retention rate.Disclosure of InterestsNone declared

BackgroundObesity is a risk factor for psoriatic arthritis (PsA) and is associated with higher disease activity [1].ObjectivesWe aimed to evaluate whether obese patients with PsA were less likely to achieve remission/low disease in a real-life multi-centre cohort.MethodsWe used data from the ReFlap study (NCT03119805)[2], which recruited consecutive adult patient with definite PsA for more than 2 years of disease duration from 14 countries. We collected demographic characteristics, self-reported weight and height, clinical data and patient reported outcomes. Remission/low disease was defined as Disease Activity in PSoriatic Arthritis (DAPSA) ≤ 4, or Minimal disease activity (MDA). Obesity was defined as body mass index (BMI) ≥ 30kg/m2. We compared patient characteristics, disease activity parameters and impact scores between patients with obesity versus non-obese. A multivariable regression model was performed for demographic variables associated with reaching each definition of remission/low disease, adjusted on age, sex, level of education, disease duration, current use of conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs).ResultsAmong 414 patients (49.3% women, mean disease duration 11.0 ±8.2 years), 119 (28.7%) had BMI ≥ 30kg/m2 (obese). Obese patients were more likely to be female, had higher swollen joint and enthesitis counts, higher self-reported pain, poorer physical function, more fatigue and poorer mental health (Table 1). Obese patients were half as likely to achieve MDA or DAPSA remission in multivariable analysis with odd ratios of 0.6 (95% confidence interval, CI: 0.3, 0.8, p=0.049) and 0.4 (95% CI: 0.2, 0.8, p=0.012), respectively for obese compared to non-obese patients (Figure 1).Table 1.Patient characteristics and remission achievement between obese and non-obese patients with psoriatic arthritisNon-obese (n=295)BMI ≥30 (n=119)pFemale, %44.361.50.002Number of comorbidities1.61 (0.93)2.83 (2.01)Tender joints, 0-683.56 (7.81)5.75 (10.0)0.018Swollen joints, 0-662.19 (7.29)1.46 (2.39)0.285Leeds enthesitis index, 0-60.48 (1.23)0.86 (1.70)0.012PGA disease activity, 0-103.90 (2.73)4.76 (2.67)0.004DAPSA14.9 (15.5)18.3 (16.1)0.045HAQ-DI, 0-30.56 (0.65)0.89 (0.70)PsAID-12, 0-103.11 (2.36)3.96 (2.50)0.001pain, 0-103.80 (2.81)4.54 (2.83)0.017fatigue, 0-103.93 (3.01)4.68 (3.17)0.025work or leisure activities, 0-103.39 (3.01)4.75 (3.11)functional capacity, 0-103.36 (2.97)4.40 (3.16)0.002depression, 0-101.88 (2.70)2.75 (3.26)0.006Mean (SD) shown unless specified otherwise. HAQ-DI: Health Assessment Questionnaire – Disability Index; PsA: psoriatic arthritis; PGA: patient global assessment of disease activity; DAPSA: Disease Activity in PSoriatic Arthritis; PsAID: Psoriatic Arthritis Impact of Disease.ConclusionIn this real-life data from 14 countries, obesity was frequent and PsA patients with BMI ≥ 30kg/m2 were more likely to be female, and had higher subjectively reported disease activity and illness impact compared to those with lower BMI. Obese patients had a two-fold lower likelihood of achieving remission/low disease defined by both MDA and DAPSA compared to non-obese patients. PsA patients with comorbid obesity may have different disease profiles from non-obese patients, and require specific management.References[1]Eder, L., et al., Obesity is associated with a lower probability of achieving sustained minimal disease activity state among patients with psoriatic arthritis. Ann Rheum Dis, 2015. 74(5): p. 813-7.[2]Gorlier, C., et al., Comparing patient-perceived and physician-perceived remission and low disease activity in psoriatic arthritis: an analysis of 410 patients from 14 countries. Ann Rheum Dis, 2019. 78(2): p. 201-208.AcknowledgementsThis study was funded by Pfizer.Disclosure of InterestsNone declared

BackgroundIn psoriatic arthritis (PsA) and rheumatoid arthritis (RA) systemic inflammation is known to cause endothelial dysfunction(1). Nailfold videocapillaroscopy (NVC) analyzes in vivo blood vessels, looking for alterations due to microvascular damage, and its application in these pathologies often highlights interesting abnormalities. PsA is characterized by lower mean capillary length and density and abnormal morphology, such as tight terminal convolutions. In RA typically elongated and dilated capillaries and prominent subpapillary plexus are described(2, 3). Differences between RA and PsA NCV patterns are known but not well defined yet(3).ObjectivesAim of our study was to evaluate the microvascular features circulation by NVC in patients affected by PsA and RA, looking for possible differences that may characterize the two diseases.MethodsWe recruited outpatients affected by PsA or RA classified according to standard criteria(4, 5) referring to the Rheumatology Unit at Sapienza University of Rome. Healthy controls (HCs) without known risk factors for nailfold capillary alterations(6) were also recruited. Patients and HCs underwent NVC with a 200x magnification lens. The following morphological parameters were considered: number of capillaries per square millimeter, alterations in length, dimension, morphology and distribution of the capillary; presence of ectatic loops, hemorrhages, flux abnormalities(7, 8). A semi-quantitative rating scale was adopted to score these changes, according to previous studies(9). The mean score for each subject was obtained by analyzing all fingers, except the thumbs.For the statistical analysis, Chi-square and Mann-Whitney tests were used. All tests were two-sided with a significance level set at pResultsWe recruited 34 patients (20 with PsA and 14 with RA) and 30 HCs. For patients, the mean age was 61,7 years (SD 15,4), median disease duration was 184 months (SD 204) and males were 18 (53%). Active or past smokers were 11 (18%), 9 (15%) suffered from arterial hypertension and 2 (0.03%) from type 2 diabetes mellitus. Raynaud’s phenomenon was present in 4 patients with PsA (20%) and 6 with RA (43%).The most frequent morphological changes were tortuous capillaries (90% in PsA and 100% in RA), single-crossing shape (90% and 86%) and bizarre capillaries (30% in both groups) while multiple crossing and ramified capillaries were present in 50% and 21 % RA patients only.With respect to HCs, we found significantly more frequent changes concerning morphology, ectatic loops, presence of hemorrhages and capillary plexus visibility in both PsA and RA patients. Moreover, patients with RA showed significantly more frequent abnormalities of the blood flow with respect to HCs. These results are shown in Table 1.Table 1.Comparison of the main NVC changes in patients and HCs.NVC ChangesHCPsARAN (%)N (%)P value vs HCsN (%)P value vs HCsMorphology3 (10%)14 (70%)p12 (86%)pEctatic loops0 (0%)11 (55%)p8 (57%)pHemorrhages2 (0.07%)1 (5%)p6 (43%)pPlexus19 (63%)10 (50%)p7 (50%)pFlux abnormalities3 (10%)6 (30%)p>0.055 (36%)pThe presence of hemorrhages was significantly higher in RA rather than in PsA patients (pConclusionOur study confirms and completes the frame of NCV alterations in PsA and RA. We described for the first time alterations in the capillary morphology and the presence of hemorrhages in both groups of patients with respect to HCs. It remains to evaluate how these findings can reflect the microvascular environment of chronic arthritis.References[1]Fromm, S et al. Arthritis Res Ther 2019[2]Lambova SN, Müller-Ladner U. Microvasc Res 2012[3]Graceffa D, et al. Arthritis 2013[4]Taylor W, et al. Arthritis Rheum 2006[5]Aletaha D, et al. Ann Rheum Dis 2010[6]Ciaffi J, et al. Microvasc Res 2020[7]Maricq HR. Arthritis Rheum 1981[8]Smith V, et al. Autoimmun Rev. 2020[9]Cutolo M, et al. J Rheumatol 2000Disclosure of InterestsNone declared

BackgroundIn psoriatic arthritis (PsA), disease activity states have been defined using the DAPSA (Disease Activity index for Psoriatic Arthritis) score (1). The disease activity states have been validated using structural progression as the gold standard (2). However, the worsening in DAPSA states has not been compared to the patient’s perspective.ObjectivesTo assess the association between a worsening in disease activity (i.e., change in DAPSA disease activity category) versus the patient’s judgement of disease worsening.MethodsReFlap (NCT03119805) was a longitudinal study in 14 countries of consecutive adult patients with definite PsA and more than 2 years of disease duration. Patients were seen twice in the context of usual care, around 4 months apart (3). Worsening in disease activity between the 2 visits was defined as a transition to a more active disease category, based on the DAPSA categories [(remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)] (1).This change was compared to (a) patient perceived-flares collected according to a patient-reported question: “At this time, are you having a flare of your psoriatic arthritis, if this means the symptoms are worse than usual?”; and (b) a worsening according to the MCID (Minimal Clinical Important Difference) question. The agreement between the definitions of worsening were calculated by frequency, Cohen’s kappa and prevalence adjusted bias adjusted kappa (PABAK). There was no imputation of missing data.ResultsOverall, 222 patients were analyzed: 127 (58.8%) were male, aged 53.5±12.3 years and with 10.8±8.3 years of disease duration. Disease activity was moderate: 35.9% had no current psoriasis skin lesions, mean tender joint count (TJC, 0-68) was 3.0±7.5, mean swollen joint count (SJC, 0-66) was 1.6±6.6, and mean DAPSA was 11.5±14.0.At 4.5±2.2 months follow-up, the proportion of DAPSA worsening was 40.1% [95% confidence interval, 33.9-46.7] (n=89). Most of the changes corresponded to patients going from remission to LDA (N=24, 27.0% of worsened patients) or from LDA to MDA (N=24, 27.0%).Patient-reported flares were reported in 27.0% [21.6-33.2] (n=60), and MCID worsening was reported in 14.0% [33.9-46.5] (n=31).Figure 1 shows the distribution of patients with worsening in DAPSA category, versus patient-defined worsening. Of the 89 patients who worsened according to DAPSA categories, 41 (46.1%) had self-perceived flares and 20 (22.5%) had worsening according to MCID. Among patients who worsened in DAPSA category, the mean change in DAPSA was higher in patients with self-perceived flares (increase of 22.2±15.0) than in patients without self-perceived flares (increase of 14.3±12.3). Of 133 patients with no worsening according to DAPSA, 114 (85.7%) had no self-perceived flares and 122 (91.7%) had no MCID worsening. The kappa [95% confidence interval] (PABAK) coefficients between DAPSA and either patient flare or MCID worsening were 0.34 [0.21-0.46] (0.40) and 0.16 [0.05-0.27] (0.28), respectively.Figure 1.Venn diagram for disease worsening between 2 visitsConclusionAfter 4 months of follow-up, 40.1% patients with long-standing PsA had a change in DAPSA category corresponding to more active disease. Most of these changes reflected transitions from remission to LDA, or from LDA to MDA. Among patients changing DAPSA category, only 46.1% reported themselves in flare at the second visit and only 22.5% reported themselves as worsened by MCID, leading to only fair (for flares) to low (for MCID worsening) agreement between the assessments of worsening. It is important to assess both disease activity, and the patient’s perspective of flare.References[1]Schoels M, et al. Ann Rheum Dis. 2016;75(5):811-8.[2]Aletaha D, et al. Ann Rheum Dis. 2017;76(2):418-421.[3]Gorlier C, et al. Ann Rheum Dis 2019;78:201-208.Disclosure of InterestsNone declared

BackgroundWith the outbreak of the SARS-CoV-2 pandemic, the rheumatologists’ attention was directed at understanding whether infected patients could have a less favorable outcome. Available data seem to indicate that the course in rheumatic patients is not dissimilar from that in the general population. However, data on the outcome of COVID-19 in patients with spondyloarthritis (SpA) are scant.ObjectivesTo describe the outcome of COVID-19 in patients with SpA in terms of hospitalization, need of oxygen therapy, and symptoms compared to a control group. The variation in disease activity before and after COVID-19 was also assessed.MethodsWe enrolled adult patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) classified according to standard criteria, that received a diagnosis of COVID-19 through molecular or rapid antigen swab tests between September 2020 and January 2022. Demographic and clinical data, including age, body mass index (BMI), smoking habit, comorbidities, rheumatic treatment at diagnosis of COVID-19, date of COVID-19 diagnosis, symptoms and additional therapy during the infection and vaccination status were collected through a questionnaire and recorded on an electronic database. Disease activity, assessed by DAPSA in PsA patients and by BASDAI and ASDAS in AS patients, was evaluated before and at the first visit after the infection. As controls, individuals with COVID-19 but with no known diagnosis of rheumatic/autoimmune disease were recruited using the “best friend” system.ResultsSixty-two patients were enrolled [43 with PsA and 19 with AS; F:M=40:22; median age 51 years, 25th-75th percentile 39.5-61; median BMI 25.5, 25th-75th percentile 21.75-28; median disease duration 90 months, 25th-75th percentile 36-192; 6 (9.7%) smokers, 37 (59.7%) non-smokers, 19 (30.6%) past smokers; 15 (24.2%) only treated with one conventional DMARD, 27 (43.5%) with bDMARDs and 20 (32.3%) with both; 44 (71%) had received no vaccine, 18 (29%) one or more doses of vaccine]. Forty-eight controls were also recruited [F:M=29:19; median age 48 years, 25th-75th percentile 41.5-57; median BMI 23.86, 25th-75th percentile 20.69-28.03; 10 (20.83%) smokers, 28 (58.33%) non-smokers, 10 (20.83%) past smokers; 43 (89.6%) had received no vaccine, 5 (10.4%) one or more doses of vaccine]. Among patients, 10 (16.1%) were hospitalized, of whom 8 (80%) required noninvasive oxygen therapy. Among controls, 7 (14.5%) were hospitalized, of whom 5 (71.4%) required noninvasive oxygen therapy. No differences were observed compared to the control group in terms of hospitalization and need for oxygen support. Likewise, the two groups did not bear any statistically significant difference in terms of symptoms (fever, dysgeusia, dyspnoea) and cardiovascular and respiratory comorbidities. BMI and smoking habit did not influence the outcome of COVID-19 in SpA patients, while a BMI of 25 or above was associated with hospitalization in the control group (p=0.0004, RR 3.417). Baseline treatment with immunosuppressants did not influence the disease outcome. DAPSA, ASDAS, and BASDAI did not significantly change after the infection (Table 1). We did not record any COVID-19-related death in either group.Table 1.Disease activity before and after COVID-19Last visit before COVID-19First visit after COVID-19*PsA (n=43)AS (n=19)PsA (n=43)AS (n=19)Remission/low disease activity, n (%)19 (44.2%)17 (89.5%)23 (53.5%)14 (73.7%)Moderate/high disease activity, n (%)11 (25.6%)0 (0%)7 (16.3%)1 (5.3%)NA 13 (30.2%)NA 2 (10.5%)NA 13 (30.2%)NA 4 (21%)* Reassessment of patients was performed 2 months (median) after COVID-19, 25th-75th percentile 1-4 monthsPsA, psoriatic arthritis; AS, ankylosing spondylitis; NA, not availableConclusionOur data show that patients with SpA do not face a worse prognosis of COVID-19 than subjects without rheumatic/autoimmune diseases and that demographic and clinical features did not influence the course of the disease.Disclosure of InterestsNone declared

BackgroundTumor necrosis factor (TNF)-α is one of principal proinflammatory cytokines involved in pathogenesis of different inflammatory arthropathies as Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS). Biotechnological drugs, represented among others by monoclonal antibodies directed against TNF-α, lead to a revolution in RA and spondylarthritis treatment. They were the first biological drugs used to treat these diseases, with good results in terms of safety and efficacy. Also because of high cost of these drugs, for some years biosimilars have been introduced in clinical practice. Biosimilars are less expensive (in Italy, less of 30% than bioriginators); they underwent to a severe process of “comparability” to assess safety and efficacy like their originators. In Italy, AIFA authorized SB4 (etanercept biosimilar), SB5 and ABP501 (adalimumab biosimilars) after passing III-phase randomized clinical trials; but real-life data and registers are lacking.ObjectivesAim of this study is to compare biosimilars and bioriginators in terms of safety and efficacy in a real-life contest.MethodsWe consequently enrolled patients, affected by inflammatory arthropathies (RA, PsA, AS) and treated with biosimilars (SB4, ABP501), belonging to any of the main biological prescribing centers in the Lazio region, from 2017 to 2020. Moreover, we enrolled patients, affected by same inflammatory diseases, but treated with corresponding originator. Clinical and laboratory data as well as disease activity indices, were collected at recruitment (T0) and after 4 (T1), 8 (T2), 12 (T3) and 24 (T4) months of therapy. Adverse events were registered.ResultsThe multicenter cohort was composed by 455 patients treated with biosimilars (SB4/ABP501 276/179; F/M 307/146; naïve 56%, median age/IQR 55/46-65) and 436 treated with originators (etanercept/adalimumab 186/259, F/M 279/157, naïve 67,2%, median age/IQR 53/43-62). No differences were found about safety, but biosimilar group presented a higher number of discontinuations due to inefficacy (pConclusionReal-life data demonstrated the same safety between biosimilars and originators but a reduced biosimilar retention rate at 24 months, about 76%. Despite their loss efficacy, biosimilars could be considered valid and safe, and a good and less expensive alternative to the originators, allowing access to these innovative treatments to a wider patient population.References[1]Feldmann, M. & Maini, R. N. Anti-TNFα therapy of rheumatoid arthritis: what have we learned? Annu. Rev. Immunol. 2001;19, 163–196.[2]McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442[3]Velayudhan J, Chen YF, Rohrbach A, Pastula C, Maher G, Thomas H, et al. Demonstration of functional similarity of proposed biosimilar ABP 501 to adalimumab. BioDrugs. 2016;30(4):339– 51.[4]Emery P, Vencovsky ́ J, Sylwestrzak A et al. Long-term safety and efficacy of SB4 (etanercept biosimilar) in patients with rheumatoid arthritis: comparison between continuing SB4 and switching from etanercept reference product to SB4. Ann Rheum Dis 2016; 75:236.Figure 1.Disclosure of InterestsNone declared