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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Background/Aims SERENA is an ongoing, prospective, non-interventional study evaluating retention, effectiveness, safety/tolerability and quality of life in > 2,900 patients with moderate to severe plaque psoriasis, active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS) treated with secukinumab at 438 sites across Europe for up to 5 years. We present interim results reporting secukinumab treatment retention and safety data through two years in PsA and AS patients. Methods This interim analysis presents data from 534 PsA and 470 AS patients enrolled (target population fulfilling eligibility criteria) and followed for at least two years. Patients (≥18 years) with active PsA or AS should have received at least 16 weeks secukinumab treatment before enrolment in the study. Retention rate was defined as percentage of patients who did not discontinue secukinumab treatment. Treatment break was defined as interruption of therapy for at least three months after last injection. Results The mean treatment duration prior to enrolment in the study was 1.0 year and 0.91 year for PsA and AS, respectively. The retention rates for secukinumab after one year since enrolment and since initiation of treatment were: PsA, 85.2% (n = 519, CI: 82.01-88.32) and 96.8% (n = 528, CI: 95.18-98.38); AS, 85.8% (n = 452, CI: 82.52-89.17) and 94.2% (n = 464, CI: 91.94-96.42), respectively. After two years since enrolment and since initiation of treatment, the retention rates were: PsA, 74.9% (n = 498, CI: 70.99-78.81) and 87.0% (n = 515, CI: 83.99-89.99); AS, 78.9% (n = 437, CI: 75.01-82.88) and 84.8% (n = 454, CI: 81.39-88.21), respectively. At baseline, the majority of PsA (79.5%; n/N=423/532) patients were receiving secukinumab 300 mg, while 97.0% (n/N=456/470) of AS patients were receiving secukinumab 150 mg. The majority of patients continued their initial secukinumab dose; “no dose change” in secukinumab treatment was reported after one and two years in the study (year one: PsA, 93.4% [n = 499] and AS, 92.6% [n = 435]; year two: PsA, 89.7% [n = 479] and AS, 87.9% [n = 413]). Secukinumab treatment break was recorded for 31 PsA patients (median [min, max] treatment break duration in days: 125.0 [61-461]) and for 42 AS patients (118.0 [61-813]), mainly due to adverse events reported in 58.1% (n = 18) and 45.2% (n = 19) of patients, respectively. The retreatment started with monthly dosing in most of the cases: PsA, 80.6% (n/N=25/31) and AS, 76.2% (n/N=32/42). No new or unexpected safety signals were reported. Conclusion Secukinumab retention rates in a real-world setting after more than two years since initiation of treatment and after two years since study enrolment indicate high persistence rates. Safety data collected prospectively for up to two years confirm the favorable safety profile of secukinumab. Disclosure K. Gaffney: Consultancies; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Lilly, Gilead, MSD, Novartis, UCB, Pfizer. Grants/research support; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. U. Kiltz: Consultancies; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. P. Sfikakis: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. N. Gullick: Consultancies; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. A. Theodoridou: Consultancies; UCB, Amgen, Novartis. J. Brandt-Juergens: Consultancies; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. Member of speakers’ bureau; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. E. Lespessailles: Consultancies; Amgen, Expanscience, Lilly, MSD. Member of speakers’ bureau; Amgen, Expanscience, Lilly, MSD. Grants/research support; Abbvie, Amgen, Lilly, MSD, UCB,. J. Fang: Other; Employee of Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis. P. Jagiello: Other; Employee of Novartis.

Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in > 2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in ≥ 2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs; 18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4]; n = 6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1]; n = 2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7]; n = 5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab. Disclosure K. Gaffney: Consultancies; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Grants/research support; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. U. Kiltz: Consultancies; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. P. Sfikakis: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. N. Gullick: Consultancies; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. G. Katsifis: Consultancies; Abbvie, Amgen, Genesis Pharma, Janssen, MSD, Novartis, Pfizer, Roche, Sobi, UCB. Honoraria; AbbVie, Aenorasis, Amgen, Genesis Pharma, Janssen, MSD, Novartis, Pfizer, Roche, UCB. A. Kandili: None. J. Brandt-Juergens: Consultancies; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Janssen. Member of speakers’ bureau; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. P. Goupille: Consultancies; AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, UCB. Honoraria; AbbVie, Amgen, Biogen, BMS, Chugai, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, UCB. N. Maiden: Member of speakers’ bureau; Eli-Lilly, UCB. M. Aassi: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. P. Jagiello: Other; Employee of Novartis.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Lupus nephritis (LN) affects a significant proportion of patients with systemic lupus erythematosus (SLE) and is characterised by increased morbidity and mortality. The updated joint EULAR/European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations for the management of LN have set as target of therapy the optimisation (preservation or improvement) of kidney function, accompanied by a reduction in proteinuria of at least 25% by 3 months, 50% by 6 months, and below 500-700 mg/g by 12 months (complete clinical response). It is currently unknown what proportion of Greek patients with LN reach these proposed targets with the current available treatments. At the same time, recent successful phase 3 trials have led to the approval of both belimumab and voclosporin for the treatment of patients with LN and have steered discussions as to whether the "induction-maintenance" paradigm should be substituted by an early combination treatment for all patients. To inform future therapeutic decisions and facilitate the positioning of these new drugs in the therapeutic algorithm of LN, the current study protocol aims to map the unmet needs in the treatment of LN in Greece, by quantifying the proportion of patients who attain the recommended treatment targets in everyday clinical practice.

The ability of microwave radiometry (MWR) to detect with high accuracy in-depth temperature changes in human tissues is under investigation in various medical fields. The need for non-invasive, easily accessible imaging biomarkers for the diagnosis and monitoring of inflammatory arthritis provides the background for this application in order to detect the local temperature increase due to the inflammatory process by placing the appropriate MWR sensor on the skin over the joint. Indeed, a number of studies reviewed herein have reported interesting results, suggesting that MWR is useful for the differential diagnosis of arthritis as well as for the assessment of clinical and subclinical inflammation at the individual large or small joint level and the patient level. MWR showed higher agreement with musculoskeletal ultrasound, used as a reference, than with clinical examination in rheumatoid arthritis (RA), while it also appeared useful for the assessment of back pain and sacroiliitis. Further studies with a larger number of patients are warranted to confirm these findings, taking into account the current limitations of the available MWR devices. This may lead to the production of easily accessible and inexpensive MWR devices that will provide a powerful impetus for personalized medicine.

To assess the possible impact conferred by co-existing variants in MEditerranean FeVer (MEFV) and other genes on systemic autoinflammatory disease (SAID) phenotype.Consecutive patients (n = 42) who underwent screening for SAIDs by next generation sequencing (NGS) targeting 26 genes, and carried at least one MEFV gene variant, were retrospectively studied. A total of 63 MEFV gene variants mainly located in exon 10 (n = 29) and exon 2 (n = 19) were identified in 21 patients with juvenile- and 21 with adult-onset disease.The candidate clinical diagnosis was Familial Mediterranean Fever (FMF) in 11, polygenic SAIDs (PFAPA, Still's disease, atypical SAPHO and inflammatory bowel disease) in 9, whereas the disease could not be clinically defined in 22 patients. Notably, 33 out of the 42 patients (79%) had at least one co-existing variants in 19 genes other than MEFV. NGS confirmed all clinical diagnoses and helped defining diagnosis in 59% of the remaining cases. Patients with undefined SAIDs (n = 9) or atypical FMF phenotype (n = 12) carried significantly more disease-causing variants in genes other than MEFV compared to patients with typical FMF (n = 9). More than one variants in these genes were significantly associated with adult-onset disease, while disease-causing variants in the same genes were also associated with an overall more severe SAID phenotype.Co-existing variants in SAID-related genes may explain the phenotypic variability of these diseases. Further studies should validate combined molecular and clinical data in order to better understand the cumulative gene dosage effect and improve the classification of these patients.