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BackgroundDigital solutions for online monitoring of chronic diseases are increasingly implemented in health care, but not all patients might have access, skills, or interest in using them. Fueled by the COVID-19 pandemic and the urgent need for remote consultations, an online website to enter patient-reported outcomes (PROs) from home (DANBIO-from-home, https://danbio.dk) was implemented on May 15th 2020 for patients with inflammatory rheumatic diseases (IRD) followed in the Danish nationwide DANBIO registry.ObjectivesTo explore the use of DANBIO-from-home during the first 1½ year after launching, with focus on a) characteristics of patients who did versus who did not access the webpage, and b) impact of patient age on time to first entry.MethodsDANBIO-from-home allows PROs to be entered remotely by computer, tablet, or smartphone after secure log-on. All patients followed in DANBIO were informed about this option by invitations sent through eBoks, a national infrastructure for electronic communication, available to 80-90% of Danish citizens. Patients were encouraged to access DANBIO-from-home before planned rheumatology consultations, or when participating in the voluntary questionnaire survey ‘You and your rheumatic disease during times with corona-virus’ (on three occasions: May 2020, Nov 2020, June 2021) (ref). Follow-up ended Dec 1st 2021.Characteristics of patients who did/did not access DANBIO-from-home during follow-up are explored by multivariable logistic regression analyses adjusted by clinical factors (gender/age-group/diagnosis/disease duration/use of biologics/HAQ/PASS). Time to first entry of PRO using DANBIO-from-home is presented as cumulative incidence curves by age group.ResultsAmong 33,776 patients with inflammatory rheumatic diseases followed in DANBIO, 68% used DANBIO-from-home at least once during follow-up (Table 1). Patients who used the system were less frequently below 40 years or above 80 years old, more frequently biologically treated and had lower HAQ-score than patients who did not use it.Table 1.Data entry, DANBIO-from-home solution N=33,776YES, 68%NO, 32%Gender, female6436Gender, male7822Age strata, yrs< 40623840-60732761-807228>803961DiagnosisRA6723AxSpA6931PsA7030Biologic treatment, yes*7327PASS, yes7129Age, yrs, median (IQR)62 (52-71)65 (50-77)Time since diagnosis, yrs, median (IQR)9 (5-16)10 (5-17)HAQ, median (IQR)0.5 (0.125-1.0)0.625 (0.125-1.25)Row percentages unless otherwise shown* latest visit before March 2020AxSpA: Axial spondyloarthritis, HAQ: health assessment questionnaire, PASS: patient acceptable symptom scale, PsA: psoriatic arthritis, RA: rheumatoid arthritisIn logistic regression analyses, factors associated with DANBIO-from-home access were: female gender (odds ratio, OR 1.2 (1.1;1.3)), age group 40-60 (1.8 (1.6;2.0)) or 61-80 yrs (1.9 (1.7;2.19) and not age >80 yrs (0.6 (0.5;0.7) with age Time to first entry was longest in in patients >80 yrs followed by the ConclusionA web-based system for secure remote entry of PROs was well-received after a nationwide launch. Patient-related factors had a substantial impact on the use. Lower use in the elderly might indicate lack of technical skills or facilities, whereas low use in younger age groups, which improved over time, is likely driven by other factors. Further analyses are planned to explore if lack of use impacts treatment outcomes.References[1]Glintborg et al, Rheumatology. 2021 Oct 9;60:SI3-SI12Disclosure of InterestsBente Glintborg Grant/research support from: AbbVie, BMS, Pfizer, Dorte Vendelbo Jensen: None declared, Lene Terslev Speakers bureau: Roche, Novartis, Pfizer, UCB, Janssen, Oliver Hendricks Grant/research support from: AbbVie, Novartis, Pfizer, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Celgene, Merck, Novartis, Simon Horskjær Rasmussen: None declared, Mogens Pfeiffer-Jensen: None declared, Thomas Adelsten: None declared, Ada Colic: None declared, Kamilla Danebod: None declared, Malene Kildemand: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Heidi Lausten Munk: None declared, Jens Kristian Pedersen: None declared, René Østgård Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi and UCB., Grant/research support from: Abbvie, Christian Møller Sørensen: None declared, Niels Steen Krogh: None declared, Jette Nørgaard Agerbo: None declared, Connie Ziegler: None declared, Merete Lund Hetland Grant/research support from: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopis, Sandoz

BackgroundPatients with inflammatory rheumatic diseases (IRD) have used self-isolation and social distancing during the pandemic to avoid SARS-CoV-19 infection (reference). In countries with unlimited and free access to SARS-CoV-19 testing, anxiety or other patient related factors might potentially increase test-frequency.ObjectivesIn patients with IRD followed in the nationwide DANBIO registry we aimed to explore clinical factors including self-isolation associated with a) a positive SARS-CoV-19 test result (‘infection’), b) higher frequency of SARS-CoV-19 testing during the first 1½ year of the pandemic.MethodsIn May-June 2020, IRD patients followed in the quality registry, DANBIO (n=36,152), were invited to participate in the voluntary online questionnaire survey ‘You and your rheumatic disease during times with corona-virus’. Patient characteristics, treatment and patient reported outcomes were captured in DANBIO and from the questionnaire. Patients were considered as self-isolating if they agreed to the question: I stay at home and avoid others as much as possible.After written consent, information on dates and SARS-CoV-19 test results (by PCR, polymerase chain reaction) during follow-up (until Nov 2021 and thus before entry of the Omicron variant) was obtained through linkage to the nationwide laboratory system.Time to first positive PCR and associated characteristics were explored by multivariable Cox regression analyses with hazard ratios, HR, adjusted for: gender/age-group/ diagnosis/biologic therapy/working/ self-isolation/HAQ/EQ-5D. Day 0 was defined as the date of first positive test in cohort (May-07-2020).Number of SARS-CoV-19 tests (median (IQR)), and characteristics associated with higher test frequency (upper quartile) was explored with multivariable logistic regression analyses (odds ratios, OR, adjustment like above).ResultsIn 10,098 included patients, 2.8% were infected during follow-up (Table 1). Age and HAQ seemed lower in infected (Table 1, Figure 1). In multivariable Cox regression analyses, male gender was associated with higher infection risk (HR 1.38 (1.05;1.80) whereas risk was lower in the age-group 61-80 years (0.60 (0.39;0.92) vs. below 40 years). Other factors were statistically insignificant.Table 1.Total populationSARS-CoV-19 testsNumber of testsPOSITIVE*NEGATIVE≥9Patient number10,098282981674062692Patient %1003977426Female, %66543977228Male, %34443977723Age, yrs, median (IQR)61 (51-70)56 (47-55)61 (51-70)55 (47-61)64 (54-72)Age, strata, yrs< 40969496623840-603898496594161-8049842988515>80247199973DiagnosisAxSpA14644966634RA63452987624PsA16893977030Other6004967931Biologic treatment, yes**38313977228HAQ, median**0.50.3750.50.3750.5EQ-5D, median0.80.80.80.80.8Self-isolating, yes84743977426Working46164965842Row percentage unless otherwise shown* At least one positive PCR before Nov 2021**May 2020AxSpA: Axial spondyloarthritis, EQ-5D: EuroQol quality of life (5D), HAQ: health assessment questionnaire, IQR: interquartile range, PsA: psoriatic arthritis, RA: rheumatoid arthritisMedian number of PCR tests was 4 (IQR 1-9). In patients with ConclusionFew patients with IRD were infected during the first 1½ years of the pandemic. Gender and age were associated with infection risk and frequency of testing. Self-isolation and a range of other clinical characteristics had no impact, which to some extent may be due to behavioral differences across age-groups.References[1]Glintborg B et al, RMD open, 2021Disclosure of InterestsBente Glintborg Grant/research support from: AbbVie, BMS, Pfizer, Dorte Vendelbo Jensen: None declared, Lene Terslev Speakers bureau: Roche, Novartis, Pfizer, UCB, Janssen, Oliver Hendricks Grant/research support from: AbbVie, Novartis, Pfizer, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Merck, Novartis, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Simon Horskjær Rasmussen: None declared, Mogens Pfeiffer-Jensen: None declared, Thomas Adelsten: None declared, Ada Colic: None declared, Kamilla Danebod: None declared, Malene Kildemand: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Heidi Lausten Munk: None declared, Jens Kristian Pedersen: None declared, René Østgård Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, Grant/research support from: AbbVie, Christian Møller Sørensen: None declared, Niels Steen Krogh: None declared, Jette Nørgaard Agerbo: None declared, Connie Ziegler: None declared, Merete Lund Hetland Grant/research support from: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopis, Sandoz

BackgroundProgrammed death 1 (PD-1) is an immune checkpoint receptor expressed by activated T-cells. Activation of the PD-1 pathway reduces T cell activation and inflammation. Targeting PD-1 in cancer can result in autoimmune disease, which highlights the importance of this pathway in balancing inflammation. Both PD-1 and its ligands are present in soluble (s) forms, and we have previously showed that sPD-1 is associated to bone erosions in rheumatoid arthritis. Spondyloarthritis (SpA) is characterized by both bone erosions and bone formation. Current evidence suggests an important interaction between the PD-1 pathway and the proinflammatory cytokine IL-17A. IL-17A is central in promoting inflammation in SpA and direct osteoclast activation leading to bone erosion. We have previously demonstrated that the PD-1 ligand, PD-L2, reduces osteoclast formation under inflammatory conditions.ObjectivesWe aimed at investigating the interplay between the PD-1 pathway and IL-17A in relation to inflammation and bone homeostasis in patients with SpA.MethodsFrom early SpA patients, plasma was collected at baseline and after 1 year of treatment with Adalimumab. From chronic SpA patients, plasma, synovial fluid (SF), peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected. Plasma and PBMCs were also collected from healthy controls (HC) for comparison. Disease activity was measured by ASDAS and progression by inflammation and new bone formation in the total spine.Facet joint biopsies were collected from SpA patients during surgery for correction of rigid hyperkyphosis. Levels of sPD-1 and sPD-L2 were measured in plasma and SF. Surface expression of PD-1 and CCR6 was evaluated on PBMCs and SFMCs. Levels of IL-17A were measured in the supernatant from stimulated PBMC cultures with recombinant human (rh)PD-1. Facet joint biopsies were stained for the presence of PD-1, PD-L1, PD-L2 and CCR6.ResultsPlasma levels of sPD-1 and sPD-L2 were equally increased in both early and chronic SpA compared to HC. Plasma levels of sPD-1 and sPD-L2 did not change following one year of treatment. In chronic SpA patients, sPD-1 levels were higher in SF than in plasma. Levels of sPD-1 and sPD-L2 in plasma and SF did not correlate with any disease activity scores or progression. Expression of PD-1 on the cell surface of PBMCs from SpA patient was comparable to healthy controls. On SFMCs, PD-1 expression was increased, supporting continuous T-cell activation in the local microenvironment. After stimulation with anti CD3/CD28, SpA PBMCs produced more IL-17A when cultured with rhPD-1 compared to healthy control PBMCs.PD-1 and CCR6 were highly present in facet joint biopsies, but PD-L2 and PD-L1 could not be detected. This supports the PD-1 pathway to play a role at the actual site of pathology.ConclusionPlasma levels of the PD-1 family is unaffected by addition of anti-TNFα antibody treatment in SpA. The early SpA cohort had a low degree of progression in structural changes in the observation period, which could explain the lack correlation with sPD-1 and sPD-L2 and disease progression. Soluble PD-1 is high in the inflamed microenvironment, where it may result in increased IL-17A production. Collectively, these data suggest that the PD-1 pathway could play a role in the pathogenesis of SpA, acting in the inflamed microenvironment.Disclosure of InterestsNone declared

Background:MTX is the first line treatment in early RA. There is robust evidence from cohort studies, but less from RCTs, that a “window of opportunity” exists over 12-16 weeks symptom duration. CR6086 is a selective prostaglandin EP4 receptor antagonist, with an immunomodulatory profile.Objectives:To test efficacy and safety of CR6086 added to MTX in early RA, DMARD-naïve patients.Methods:Patients with RA (ACR/EULAR 2010 criteria), < 1 year from symptom onset and naïve to DMARDs were randomized to oral CR6086 30, 90, 180mg, or placebo bid and oral MTX (20mg weekly) for 13 weeks (NCT03163966). Primary endpoint was the ACR20 response rate: 240 patients were needed to detect a difference among groups, with 50% responders on placebo and 70% on the 90mg CR6086 target dose. Pairwise comparisons of proportions were performed, with nonresponder imputation for withdrawals. A subgroup of patients underwent dynamic contrast-enhanced (DCE) MRI for quantification of synovitis at MCP and wrist joints, evaluated as DEMRIQ-ME and DEMRIQ-vol.Results:The ITT population included all 244 randomized patients receiving at least one dose of study drugs (59 CR6086 30mg/MTX, 60 CR6086 90mg/MTX, 63 CR6086 180mg/MTX, 62 placebo/MTX). Safety was good with no increased rate of infections or other disorders; however, there were more minor upper GI adverse events (AEs) with CR6086, and increased dropouts due to AEs with the 180mg dose (9/63, 14.3% vs 1.7-3.4% in other groups). There were more ACR20 responders with MTX monotherapy than predicted (59.7%) and thus the 10.3% difference with the 90mg target dose (70.0%) was not significant. The low 30mg dose was no better than placebo (55.9%), while the high 180mg dose did not provide additional benefit compared with 90mg (74.0% net of dropouts). CR6086 90mg and 180mg induced a significant improvement in MRI, compared with placebo (Fig. 1). In a post-hoc analysis in patients < 6 months from symptom onset (ACR definition of early RA: 98/244, 40.2%), MTX monotherapy exerted a large 76% ACR20 response rate that precluded potentiation. Conversely, in patients of 6-12 months disease duration (146/244, 59.8%) ACR20 responders were 48.6% with MTX monotherapy vs 68.4% with 90mg, i.e. a 19.8% difference as postulated, with proportional differences in secondary endpoints (Tab. 1).Conclusion:There was no benefit demonstrated for CR6086 added to MTX in the study cohort as a whole. However, in a post-hoc analysis, enhanced responses were observed with CR6086 90mg bid added to MTX in patients >6 months disease duration. This generated the hypothesis that addition of CR6086 90mg bid may benefit in RA patients initiating MTX after the window of opportunity, to be tested in further studies.Table 1.Patient characteristics & pregnancy outcomesSymptom onset (principal analysis)Symptom onset 6-12 months(post-hoc analysis)*Placebo+MTX(N=62)CR6086 90mg+MTX(N=60)Placebo+MTX(N=37)CR6086 90mg+MTX(N=38)ACR20, %59.7%70.0%48.6%68.4%ACR50, %33.9%38.3%29.7%39.5%ACR70, %17.7%23.3%10.8%28.9%DAS28 (CRP) 12.9%20.0%8.1%18.4%CDAI ≤2.8, %8.1%11.7%5.4%15.8%SDAI ≤3.3, %6.5%10.0%2.7%15.8%Boolean-based remission, %6.5%6.7%2.7%10.5%*In patients with symptom onset Figure 1.Change in MRI (DEMRIQ-ME#) after 13 weeksDisclosure of Interests:Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Ivanova Delina2 Delina: None declared, Minodora Mazur: None declared, Massimo D’Amato Employee of: Rottapharm Biotech, GIAMPAOLO GIACOVELLI Employee of: Rottapharm Biotech, Federica Girolami Employee of: Rottapharm Biotech, Marek Krogulec: None declared, René Østgård: None declared, Asger Reinstrup Bihlet Shareholder of: Nordic Bioscience A/S., Olga Kubassova Shareholder of: IAG, Image Analysis Group, Consultant of: Novartis, Takeda, Lilly, Employee of: IAG, Image Analysis Group, Lucio Rovati Shareholder of: Rottapharm Biotech, Employee of: Rottapharm Biotech, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB