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OBJECTIVE To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. METHODS Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. RESULTS Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P

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

Thank you for the interest1 in our recent publication, in which we explored treatment outcomes following a Danish mandatory switch from originator to biosimilar etanercept (SB4, 50 mg) in routine care.2 We showed that of the 2061 patients who were receiving originator etanercept and thus were eligible for the switch, as many as four of five (79%) switched to the biosimilar, despite the continued availability of the originator drug (as 25 mg pen or 50 mg powder solution). Among the patients who switched, we observed high retention rates of the biosimilar. The 6-month …

Objectives: Touch screens for entering patient-reported outcomes (PROs) are available at all Danish departments of rheumatology reporting to the nationwide DANBIO registry. This project comprises two substudies in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (AxSpA), aiming to (A) investigate the feasibility of first line patient recruitment for research via touch screens, and (B) compare PROs collected at hospital versus at home, including patient preferences. Method: Substudy A: using a touch screen, patients answered whether we could contact them about a clinical research project (yes/no). Characteristics of patients who accepted/declined were explored using chi-squared and Mann–Whitney U-tests. Substudy B (randomized crossover agreement study): a random sample of patients from the accepting group in substudy A was contacted by telephone. According to prespecified power and sample size estimation, 56 patients were included. After randomization, 50% of patients entered PROs and information on comorbidities and lifestyle from home and then at hospital, and 50% first from hospital and then at home. Finally, they stated their preference for data entry (hospital/home/equally good). Differences in PROs entered from home and in the hospital were compared (limits of agreement, 95% confidence intervals, and intraclass correlation coefficients). Results: The touch-screen invitation was accepted by 428/952 patients (45%). Patients who accepted and those who declined had similar PROs and demographics. Substudy B was completed by 42 patients (22 RA, 20 AxSpA). They had no significant differences between PROs and lifestyle/comorbidity data entered from home and hospital, except for AxSpA patients on the Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Disease Activity Index item 5. The preferred method of data entry was hospital (10%), home (50%), and equally good (40%). Conclusion: Touch screens seem feasible for first line research recruitment. PROs collected from home were similar to the touch-screen solution. Patients preferred data entry from home.

Background:Smoking is a known risk factor for rheumatoid arthritis (RA). It is largely unknown whether smoking has any impact on disease activity and treatment outcomes (e.g. achieving remission on methotrexate and time to first biological disease modifying anti-rheumatic treatments (bDMARD)) in early RA with a modern treat-to-target strategy.Objectives:To explore if smoking was associated with treatment outcomes in newly diagnosed patients with RA starting first conventional synthetic (cs)DMARDs in routine care.Methods:Observational cohort study. Adult patients with RA starting first csDMARD during year 2010-2018 were identified in the Danish nationwide quality registry, DANBIO. Smoking status (current/never/previous) upon start of csDMARD (=baseline), disease activity, 1-year treatment outcomes and bDMARD treatment were retrieved from DANBIO. Data were censored Oct 2019.Impact of smoking status was explored for the following outcomes: 1) median baseline disease activity baseline, 2) remission at 1-year (logistic regression analyses), 3) time to first bDMARD (Cox-regression analyses). Regression analyses were adjusted for gender and age.Results:Among 9515 patients, 8647 (91%) had available smoking status (Current 23%/never 50%/previous 27%) and were included. Baseline disease activity was independent of smoking status (Table 1). First line csDMARD was methotrexate in 91% of patients. Compared to never smokers, the current smokers were more often men, younger and sero-positive for IgM-RF and anti-CCP.Table 1.Patient characteristics and disease activity at baseline and 1 year stratified by smoking status. Numbers are medians (IQR) unless otherwise stated.Smoking statusCurrentNeverPreviousBaselinePatient numbers, N200743082332Age, yrs58 (49-66)61 (48-71)62 (52-70)Female, %627163IgM-RF positive, %715465Anti-CCP positive, %715365DAS284.4 (3.4-5.3)4.4 (3.4-5.3)4.3 (3.3-5.3)CDAI18.7 (11.7-27.3)18.4 (10.9-27.4)18.5 (10.4-27.6)VAS patient global, mm60 (35-81)55 (30-77)55 (31-78)1 yearPatient number, N179338372053DAS282.6 (1.9-3.7)2.3 (1.7-3.4)2.5 (1.8-3.4)CDAI6.4 (2.8-12.5)4.9 (1.8-10.3)5.4 (2-10.8)DAS28-remission, %495753CDAI-remission, %273533VAS patient global, mm37 (14-67)29 (10-57)30 (11-58)DAS28-response: DAS28(CRP)≤2.6; CDAI-remission: CDAI≤2.8Never and previous smokers had higher odds of remission at 1 year’s follow-up compared to current smokers. In adjusted Cox regression analyses, baseline smoking was associated with shorter time to start of first bDMARD (Table 2).Table 2.Impact of baseline smoking status on treatment outcomesComparisonOdds Ratio (95% CI)pDAS28-remission 1 yr, yes vs. no*Never vs. current smoker1.43 (1.27;1.62)Previous vs. current1.14 (0.99;1.30)0.07CDAI remission 1 yr, yes vs. no*Never vs. current1.53 (1.34;1.75)Previous vs. current1.29 (1.11;1.50)ComparisonHazard Ratio (95% CI)pStart of bDMARD duringfollow-up**Never vs current smoker0.85 (0.76;0.96)0.006Previous vs. current1.05 (0.93;1.19)0.4*Logistic regression analyses (adjusted for gender and age)** Cox regression analyses (adjusted for gender and age)Conclusion:In this observational study of >8000 patients with RA starting a first csDMARD, current smoking was associated with lower odds of achieving remission on methotrexate and higher chance of having started bMDARD compared to never smokers. Seropositivity may be an intermediate variable. Further analyses are planned to study impact of comorbidities and other confounding factors.Acknowledgments :Thank you to all patients and departments who contribute to the DANBIO registryDisclosure of Interests: :Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Oliver Hendricks Grant/research support from: Pfizer, MSD, Ada Colic Consultant of: Advisory board Sanofi, Hanne Merete Lindegaard: None declared, Rabiah Ahmed: None declared, Anne Gitte Loft Grant/research support from: Novartis, Consultant of: AbbVie, MSD, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer and UCB, Gina Kollerup Speakers bureau: Eli Lilly, Marlene Andersen: None declared, Jolanta Grydehøj: None declared, Johnny Raun: None declared, Toke Thorgrimsen: None declared, Kasper Mortensen: None declared, Line Uhrenholt Speakers bureau: Abbvie, Eli Lilly and Novartis (not related to the submitted work), Dorte Jensen: None declared, Iben Ruge Grant/research support from: Novo Nordisk Foundation, Maren Kalisz: None declared, Kamilla Danebod: None declared, Niels Lomborg: None declared, Niels Steen Krogh: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis

ObjectivesReal-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised.MethodsObservational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted).Results1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months’ preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers’ clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective.ConclusionSeventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

Background:During the COVID-19 pandemic, widespread changes in how we work have been observed. Working from home is not an option for everyone. At work it may be difficult to keep social distance, which may lead to fear and anxiety of being infected with SARS-CoV-19 or of spreading the virus.Objectives:To explore frequency of anxiety and concerns related to work in patients with inflammatory rheumatic diseases(IRD) during the COVID-19 pandemic and to identify patient and disease characteristics associated with increased anxiety.Methods:Patients in routine care followed in the nationwide Danish DANBIO registry were invited to answer an on-line questionnaire regarding current rheumatic disease activity, behavior and anxiety including current work-status and -concerns. Responses were linked to patient data previously recorded in DANBIO. Clinical factors associated with work-related concerns (completely/mostly agree versus neither/nor, completely/mostly disagree) were explored with multivariable logistic regression.Results:Among 14,758 respondents (38% of eligible patients), 5,950 patients (40%) were currently working (60% full time/31% part time/9% self-employed) (61% female, 53% rheumatoid arthritis/19% psoriatic arthritis/20% axial spondyloarthritis/9% other). Although 68% reported that the workplace helped to make necessary interventions, work-related concerns and anxiety were frequent. Thus, 22% found it difficult (completely/mostly agree) to keep physical distance at work and 20% were worried about going to work (Figure 1).Factors associated with concerns about going to work were female gender, longer education, other chronic conditions, biological therapy, and higher (=poorer) EQ-5D, whereas diagnosis was without significance. Similar patterns were found for other work-related concerns (not shown).Conclusion:In this cohort of >5,000 patients with inflammatory rheumatic diseases followed in a nationwide registry, during the COVID-19 pandemic anxiety and concerns related to the work situation were frequent, especially in women and patients treated with biologicals, with other chronic diseases and with poor quality of life.References:[1]Glintborg et al, 2021, https://rmdopen.bmj.com/content/rmdopen/7/1/e001505.full.pdfTable 1.Factors associated with being worried (agree versus disagree) to go to work (Figure 1, panel F). Multivariable logistic regression analysesOdds ratio (95% CI)pGenderfemale1male0.45 (0.38;0.54)Age, years>40140-601.12 (0.87;1.44)0.4>600.89 (0.67;1.20)0.5EducationLong1No/short0.80 (0.69;0.93)0.005Living alone, yes0.97 (0.79;1.20)0.8Other chronic condition, yes1.37 (1.17;1.59)Biological therapy1.36 (1.17;1.58)DiagnosisRheumatoid arthritis1Psoriatic arthritis1.21 (0.99;1.48)0.06Axial spondyloarthritis1.03 (0.84;1.28)0.8Other1.17 (0.89;1.54)0.3PASS, yes*1.03 (0.85;1.25)0.7SmokingCurrent1Previous1.17 (0.94;1.47)0.2Never1.10 (0.90;1.35)0.4EQ5D**0.03 (0.02;0.06)*patient acceptable symptom state, **European Quality of Life, 5 dimensionsDisclosure of Interests:Bente Glintborg Grant/research support from: AbbVie, BMS, Pfizer, Dorte Vendelbo Jensen: None declared, Sara Engel: None declared, Lene Terslev Speakers bureau: AbbVie, Janssen, Roche, Novartis, Pfizer, MSD, BMS and GE, Mogens Pfeiffer Jensen: None declared, Oliver Hendricks: None declared, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, 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, 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 L. 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. MLH chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs the EuroSpA research collaboration, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis.

Background:The COVID-19 pandemic has caused lockdown, reduced access to face-to-face consultations, anxiety about taking immunosuppressive agents and self-isolation1 which potentially impact rheumatic disease control negatively. However, changes in behavior including self-protection strategies during the ongoing pandemic and impact on rheumatic disease activity have only been scarcely described.The first COVID-19 wave hit Denmark in March 2020 followed by a gradual re-opening from mid-April and the second surge began in the late autumn of 2020.Objectives:To describe changes over time in self-protection strategies and health behavior during the first 8 months of the COVID-19 pandemic and to explore impact on self-reported disease activity and quality of life (=patient reported outcomes, PROs) in patients with inflammatory rheumatic disease (IRD) in DANBIO.Methods:Patients were invited to answer two on-line questionnaires regarding current behavior and disease specific PROs: One in June 2020 (including also questions regarding behavior in March 2020), and one in November 2020. Responses were linked to PROs collected as part of routine care before March 2020 (=Before) in DANBIO. For each PRO, changes (=delta values) between the two timepoints were calculated in individual patients.Results:Overall, 7,836 patients (22% of eligible patients) answered both questionnaires and were included (rheumatoid arthritis(RA): 5270(67%), psoriatic arthritis(PsA): 1217(15%), axial spondyloarthritis(AxSpA): 932(12%), other IRD: 417(5%). Patients reported highest levels of anxiety and self-protection in March with an improvement in June that was largely unchanged in November (Figure 1), e.g. proportions staying at home avoiding others as much as possible (completely or mostly agree) were 87%/49%/51% in March/June/November, respectively (Figure 1, Panel C).Disease activity and proportions of patients reporting acceptable symptom state remained stable at the three time points (Table 1), with all median delta values being close to zero (not shown).Conclusion:In this large cohort of patients with inflammatory rheumatic diseases followed in the nationwide DANBIO registry, COVID-19 related self-protection strategies were highest in March 2020, but more than half of the patients also reported self-isolation in June and November. We found no negative impact of the pandemic on patient-reported outcomes, which remained largely unchanged and were similar to before the pandemic. The latter finding probably reflects that few patients reduced or withdrew from treatment due to fear of COVID-19.1References:[1]Glintborg et al, 2021, https://rmdopen.bmj.com/content/rmdopen/7/1/e001505.full.pdfTable 1.Patient reported outcomes before March, in June and in November 2020 in patients with IRD. N=7,836Before*June 2020Nov 2020Patient VAS global, mm30 (12-58)28 (10-54)29 (10-55)Patient VAS pain, mm27 (11-51)28 (11-51)29 (11-52)HAQ0.50 (0.13-1.0)0.50 (0.13-1.00)0.50 (0.13-1.00)EQ-5D0.80 (0.72-0.86)0.79 (0.71-0.86)0.80 (0.71-0.86)PASS, yes73%75%76%Numbers are median (IQR) unless otherwise stated*Latest registration in DANBIO before March 2020Patient characteristics for RA/AxSpA/PsA/Other: female, %: 70/53/44/69. Age, years, median(IQR): 67(59-74)/62(54-69)/56(46-65)/59(50-68)Abbreviations: EQ-5D: Quality of life, 5 dimensions, HAQ: health assessment questionnaire, PASS: patient acceptable symptom state, VAS: visual analogue scaleDisclosure of Interests:Bente Glintborg Grant/research support from: AbbVie, BMS, Pfizer, Dorte Vendelbo Jensen: None declared, Sara Engel: None declared, Lene Terslev Speakers bureau: AbbVie, Janssen, Roche, Novartis, Pfizer, MSD, BMS and GE, Mogens Pfeiffer Jensen: None declared, Oliver Hendricks Grant/research support from: AbbVie, Novartis, Pfizer, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB., Grant/research support from: Research grants: Abbvie, BMS, Celgene, Merck, Novartis, Simon Horskjær Rasmussen: None declared, Thomas Adelsten: None declared, Kamilla Danebod: None declared, Ada Colic: 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: Research grants: Abbvie, Christian Møller Sørensen: None declared, Niels Steen Krogh: None declared, Jette Nørgaard Agerbo: None declared, Connie Ziegler: None declared, Merete L. 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. MLH chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs the EuroSpA research collaboration, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis.

Objectives In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA). Methods Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months’ remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication). Results Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months’ remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched. Conclusion This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.

Background:In the DANBIO quality registry in Denmark, patients with rheumatoid arthritis (RA) psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) have reported Patient Reported Outcomes (PROs) including the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) for nearly twenty years as part of routine care. Patients’ feedback have stressed a need for a shorter registration of disability (1). While the shorter Multidimensional Health Assessment Questionnaire (MDHAQ) is preferred by patients, the original HAQ-DI is the preferred tool in observational studies. Thus, a conversion algorithm between the MDHAQ and HAQ-DI scores is warranted.Objectives:To develop and validate a simple conversion algorithm between MDHAQ and HAQ-DI scores in RA, PsA and axSpA patients.Methods:Patients registered in DANBIO with a diagnosis of RA, PsA or axSpA who had completed both HAQ-DI and MDHAQ simultaneously at a visit +/- 30 days from start of conventional synthetic (cs)DMARD or biological (b)DMARD were eligible for the analysis, and randomly divided into development and validation cohorts stratified by diagnosis. The conversion algorithm was developed in the RA development cohort using linear regression with HAQ-DI as the dependent variable and MDHAQ as the independent variable. The predicted HAQ (pHAQ) scores were then calculated by applying the conversion algorithm to the MDHAQ scores in the RA, PsA and axSpA validation cohorts. The pHAQ was validated against the HAQ-DI in the validation cohorts regarding criterion, correlational and construct validity.Results:We included 8983/4410/1760 patients with RA/PsA/axSpA, respectively. The conversion algorithm pHAQ=0.15+MDHAQ*1.08 had the best fit (R2=0.83) in the RA development cohort.Criterion validity: The correlation coefficients between HAQ-DI/pHAQ and patient global score at baseline were 0.66/0.65. In groups of patients with high and low disability (defined as patient global score ≥50), standardized mean difference was -1.4 for HAQ-DI, and -1.4 for pHAQ.Correlational validity: Correlation coefficients between HAQ-DI/pHAQ and ΔHAQ-DI/ΔpHAQ between baseline and first follow-up visit were r=0.91 and r=0.87, respectively. Correlation coefficients between HAQ-DI/pHAQ and pain score, DAS28CRP and physician global score were 0.63/0.64, 0.55/0.55 and 0.34/0.34, respectively. A Bland-Altman plot showed good agreement of HAQ-DI and pHAQ across all functional states.Construct validity: HAQ-DI/pHAQ at the first follow-up visit after baseline was comparable between Patient Acceptable Symptom State groups (PASS=No: mean 1.17 vs 1.18/PASS=Yes: 0.55 vs 0.60). Similar results were seen for the external anchor (Figure 1).In PsA and axSpA validation cohorts, similar results were found.Conclusion:A conversion algorithm from MDHAQ to HAQ-DI was developed in ≈ 4500 RA patients. In separate large validation cohorts of RA, PsA and axSpA patients, the predicted HAQ calculated from the MDHAQ scores showed good criterion, correlational and construct validity comparable to the original HAQ-DI. The results suggest that for research purposes the MDHAQ can be converted to HAQ-DI if a full HAQ-DI has not been performed.References:[1] Primdahl J. et al. Arthritis Care Res 2019 (in press).Acknowledgments:The authors thank all Danish patients and Departments of Rheumatology, who conscientiously report to the DANBIO registry.Disclosure of Interests:Elisabeth Svensson: None declared, Katja Løngaard: None declared, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Rikke Meincke: None declared, Jens Kristian Pedersen: None declared, Lene Dreyer: None declared, Niels Steen Krogh: None declared, Dorte Vendelbo Jensen: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis

Background In Denmark, patients (pts) treated with originator etanercept (ETA) 50 mg SC conducted a mandatory non-medical switch to biosimilar SB4 in April 2016 (switchers). Pts treated with 25 mg ETA or 50 mg powder-solution were not mandated to switch (non-switchers). Some switchers resumed ETA during follow-up (back-switchers). Objectives To investigate the frequency of back-switching after the non-medical switch from ETA to SB4, and in back-switchers to study, 1) baseline characteristics at the time of initial switch (ETA->SB4), 2) reasons for SB4 withdrawal, 3) changes in disease activity during treatment with SB4 and after back-switching. Methods Patient data were retrieved from the DANBIO registry (censored August 2017). For back-switchers, disease activity at the start of SB4 (=baseline) and at the time of back-switching to ETA were compared, and changes in disease activity between the two time points were calculated (=delta values), stratified by indication (RA/PsA/AxSpA). Baseline characteristics of back-switchers were compared to the rest of the switch population (Chi-sq, Mann-Whitney U-test). Abbreviations are shown in table 1. Results 1641 pts switched from ETA to SB4. Of these, 299 (18%) withdrew SB4 therapy during 1 year follow-up and either switched back to ETA (n=120, 7%), started another bDMARD (n=104), died (n=9), were lost to follow-up (n=1) or did not re-start bDMARDs (n=65). Among the 120 back-switchers, SB4 was withdrawn due to LOE (52%), AE (39%), or other/unknown reasons (9%). The reasons for withdrawal of SB4 in back-switchers are listed in table 1. No major safety events occurred. The median time on SB4 before back-switching was 120 (IQR 73–193) days, and the time between stop of SB4 and re-start of ETA was 11–1 days. Baseline characteristics of back-switchers vs the rest of the switch population were similar (all p>0.05). Among back-switchers who stopped SB4 due to LOE, PGA increased during SB4 treatment, whereas CRP and SJC were largely unchanged (table 1). At the date of censoring, 104/120 back-switchers (87%) were still treated with originator ETA (median treatment duration 236 (155–302) days). Conclusions In a nationwide cohort of 1621 arthritis patients that were switched from ETA to SB4, 7% switched back to ETA. Back-switchers had no distinct clinical or disease characteristics upon start of SB4. AEs prior to back-switching were largely unspecific. In pts who withdrew SB4 due to LOE, PGA had increased. Reasons for back-switching appeared to be predominantly subjective rather than objective (nocebo effect). Originator drug was still available (25 mg or 50 mg powder-solution), which may have encouraged back-switching. References [1] Glintborg, et al. Arthritis Rheum2017;69(suppl 10). [2] Glintborg, et al. Abstract, EULAR2018. Acknowledgements Partly sponsored by Biogen Disclosure of Interest B. Glintborg Grant/research support from: Abbvie, Biogen, Pfizer, I. Sorensen: None declared, E. Omerovic: None declared, F. Mehnert: None declared, N. Manilo: None declared, K. Danebod: None declared, D. Jensen: None declared, H. Nordin: None declared, A. G. Loft Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, O. Hendricks Grant/research support from: Abbvie, Roche, Novartis, S. Chrysidis: None declared, B. Andersen: None declared, J. Raun: None declared, H. Lindegaard: None declared, J. Espesen: None declared, S. Jakobsen: None declared, I. M. Hansen Grant/research support from: Roche, E. Dalsgaard: None declared, D. Pedersen: None declared, S. Kristensen: None declared, A. Linauskas: None declared, L. Andersen: None declared, J. Grydehoj: None declared, N. Krogh: None declared, M. Hetland Grant/research support from: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB

Background A cohort of routine care rheumatoid arthritis (RA) patients in sustained remission had biological disease-modifying anti-rheumatic drugs (bDMARDs) tapered according to a treatment guideline. Little is known about predictors of successful tapering and discontinuation of bDMARDs. Objectives We studied: 1) the proportion of patients whose bDMARD could be successfully tapered or discontinued; 2) unwanted consequences of tapering/discontinuation; 3) potential baseline predictors of successful tapering and discontinuation. Methods One-hundred-and-forty-three patients with sustained disease activity score (DAS28-CRP)≤2.6 and no radiographic progression the previous year were included. bDMARD was reduced to 2/3 of standard dose at baseline, ½ after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP≥2.6 and DAS28-CRP≥1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results One-hundred-and-forty-one patients completed 2 year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving 2/3 of standard dose, 39 (28%) ½ dose and 22 (16%) having discontinued; 54 patients (38%) were receiving full dose. DAS28-CRP0–2yrs was 0.1((−0.2)–0.4) (median(interquartile range)) and mean Total-Sharp-Score0–2yrs was 0.01 (1.15) (mean(SD)). Radiographic progression was observed in 9 patients (7%). Successful tapering was independently predicted by: ≤1 previous bDMARD, male gender, low baseline MRI combined inflammation score and low MRI combined damage score. Negative IgM-rheumatoid factor predicted successful discontinuation. The association between potential predictors and the proportion of patients with successful tapering of bDMARDs is shown in figure 1. Conclusions By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. IgM-RF was an independent predictor for successful discontinuation of bDMARDs. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and MRI combined damage scores were independent predictors for successful tapering. Disclosure of Interest None declared

Objectives A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation. Methods One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation. Conclusion By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Background Collection of patient-reported outcomes (PROs) is an important aspect of modern treatment strategies. Electronic capture in waiting areas by touch screens is part of routine care in the Danish DANBIO registry 1 . It is not known whether this data collection can be replaced with electronic data entry from home. Objectives To test the feasibility of online patient recruitment via touch screens and to investigate if electronic reporting of PROs from home (ELECTOR IT-platform) is comparable to reporting completed at the hospital among patients with rheumatoid arthritis (RA) or axial spondyloarthritis (AS). Methods Patients with RA or AS were recruited via touch screens and randomized to one of two groups by a pre-computed list generated through DANBIO; the first group completing the PROs at home and then at the hospital-site, and vice versa for the second group. All patients completed the Health Assessment Questionnaires (HAQ), the Visual Analogue Scales (VAS) for fatigue, pain and global health and the annual visit questions. Furthermore, AS patients completed the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the BAS Function Index (BASFI). Pearson9s Chi-square test, independent samples t-test and Mann-Whitney U test were calculated. Smallest detectable differences (SDDs), 95% confidence intervals (CIs) and intra-class correlation coefficients (ICCs) were calculated. Clinicaltrials.gov identifier: NCT02818478. Results A total of 952 patients received invitation, 45% accepted, 127 patients were contacted by phone, and 56 (44%) gave consent to participate. 22 patients with RA and 20 patients with AS completed the trial. All differences between scores from home vs hospital were smaller than SDD, and all were non-significant (p Conclusions Recruitment of patients for a randomized trial via touch screens was feasible. PROs collected from patients9 own devices at home generated results comparable to results obtained from the existing touch-screen solution and were preferred by the patients. References Schefte et al. (2010). Disclosure of Interest A. E. Secher: None declared, B. Glintborg Grant/research support from: AbbVie, H. Gudbergsen Speakers bureau: MSD and Pfizer, N. Krogh: None declared, D. Jensen: None declared, I. Sorensen: None declared, R. Christensen: None declared, M. Skougaard: None declared, M. Hetland Grant/research support from: AbbVie, BMS, MSD, Pfizer, UCB, Biogen, Orion

Thank you for the interest in our publication based on data from the Danish DANBIO registry regarding 2061 patients who were eligible for a mandatory non-medical switch from originator to biosimilar etanercept in routine care.1 2 The marketing of biosimilars has changed the landscape of the biological drugs with the potential for huge cost reductions, most markedly if patients may be switched from an ongoing successful treatment with the expensive originator to a much cheaper biosimilar. Thus, up to 75% price reduction has been experienced in Denmark so far with no evidence of increased use of health resources.3 The outcomes of a non-medical switch of etanercept in the real-world setting are, however, largely unknown, since prevous publications on switching in routine care have included limited numbers of patients. The aim of the study was therefore to investigate the effectiveness of a large-scale, …

OBJECTIVES: To estimate the prevalence of Danish RA patients currently on biologic monotherapy and compare the effectiveness and drug adherence of biologic therapies applied as monotherapy.METHODS: All RA patients registered in the Danish biologics database (DANBIO) as receiving biologic DMARD (bDMARD) treatment as monotherapy without concomitant conventional synthetic DMARDs (csDMARDs) during the study period 1 May, 2011 through 30 April 2013 were eligible for inclusion. All patient files were checked to ensure that they were in accordance with the treatment registration in DANBIO. Descriptive statistics for prevalence, effectiveness and drug adherence of bDMARD monotherapy were calculated.RESULTS: Of the 775 patients on bDMARD monotherapy, adalimumab (21.3%), etanercept (36.6%) and tocilizumab (15.3%) were the most prevalent biologic agents administered. At the 6-month follow-up, the overall crude clinical disease activity index remission rate in patients still on a biologic drug was 22%, the 28-joint DAS remission rate was 41% and the response rate of those with a 50% improvement in ACR criteria was 28%. At the 6-month follow-up, the drug adherence rates were similar for the different bDMARDs, with the exception of infliximab, which had significantly poorer drug adherence (P < 0.001). The overall drug adherence (except for infliximab) was approximately 70% after 2 years.CONCLUSION: Nearly one in five (19%) biologic treatments for RA was prescribed in Denmark as monotherapy, of which 70% were on monotherapy from bio-initiation and 30% were on monotherapy after cessation of a concomitant csDMARD. Acceptable drug adherence and remission rates were achieved with bDMARDs. With the exception of infliximab, no statistically significant differences were observed between anti-TNFs and biologics with other modes of action.

Objective.To investigate baseline characteristics associated with radiographic progression and the effect of disease activity, drug, switching, and withdrawal on radiographic progression in tumor necrosis factor (TNF) inhibitor-naive patients with rheumatoid arthritis (RA) followed for about 2 years after anti-TNF initiation in clinical practice.Methods.DANBIO-registered patients with RA who had available radiographs (anti-TNF initiation and ∼2 yrs followup) were included. Radiographs were scored, blinded to chronology with the Sharp/van der Heijde method and linked with DANBIO data. Baseline characteristics were investigated with univariate regression and significant variables included in a multivariable logistic regression analysis with ± radiographic progression [Δ total Sharp score (TSS) > 0] as dependent variable. Effect of time-averaged C-reactive protein (CRP), 28-joint Disease Activity Score with CRP (DAS28-CRP), and treatment status at followup were investigated with univariate regression analysis.Results.The study included 930 patients. They were 75% women, 79% positive for IgM-rheumatoid factor (IgM-RF), median age was 57 yrs (range 19–88), disease duration 9 yrs (1–59), DAS28-CRP 5.0 (1.4–7.8), TSS median 15 [3–45 interquartile range (IQR)] and mean 31 (SD 40). Patients started treatment with infliximab (59%), etanercept (18%), or adalimumab (23%). At followup (median 526 days, IQR 392–735), 61% were treated with the initial anti-TNF, 29% had switched TNF inhibitor, and 10% had withdrawn. Twenty-seven percent of patients had progressed radiographically. ΔTSS was median 0.0 [0.0–0.5 IQR/mean 0.6 (SD 2.4)] units/year. Higher TSS, older age, positive IgM-RF, and concomitant prednisolone at baseline were associated with radiographic progression. Time-averaged DAS28-CRP and time-averaged CRP, but not type of TNF inhibitor, were associated with radiographic progression. Patients who stopped/switched during followup progressed more than patients who continued treatment.Conclusion.High TSS, older age, IgM-RF positivity, and concomitant prednisolone were associated with radiographic progression during 2 years of followup of 930 anti-TNF–treated patients with RA in clinical practice. High disease activity and switching/stopping anti-TNF treatment were associated with radiographic progression.

Pelvic pain in pregnancy appears to be a problem that is increasing. This study was undertaken to describe and analyze the relationship between subjective symptoms, daily disability, and clinical findings in women with symptom-giving pelvic girdle relaxation in pregnancyOut of 1600 pregnant women 238 had pelvic pain. After a clinical examination 11 women were excluded due to low back pain. The rest, 227 women, was considered having symptom-giving pelvic girdle relaxation during pregnancy.Symptom-giving pelvic girdle relaxation in pregnancy seriously interferes with many activities of daily living such as housekeeping, walking, working, and sexual life. The women's statements of pelvic pain are well correlated to the number of positive clinical tests.Symptom-giving pelvic girdle relaxation in pregnancy causes considerable disabilities concerning daily activities.

Background According to national guidelines issued in 2015, a non-medical switch from originator infliximab (IFX) to biosimilar IFX was conducted in all Danish patients with inflammatory rheumatic diseases treated in routine care. Objectives To investigate effects of the switch on serum (s) IFX and anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA), axial spondyloarthrits (SpA) and psoriatic arthritis (PsA). Methods We included originator infliximab treated patients, who switched to and were treated with biosimiilar infliximab for >2 months with 2 available trough level serum samples (baseline immediately before switching/follow-up 2–4 months after switching time of 2nd–4th infusion). Patients stopping treatment earlier were not included. Trough sIFX 30AU/l median-high. sIFX and ADA were analyzed using automated in-house assays at OUS-Radiumhospitalet. Characteristics and outcomes were registered in the DANBIO registry. Remission was defined by disease activity indices (DAS28 Results 96 pts (192 samples) from 4 departments (49 RA, 27 SpA, 10 PsA, 10 other) were included (age 52 (43–62) years, 47% women). Previous IFX treatment duration was 7.5 (5.1–10.3) years. Follow-up was after 81 (71–90) days. 58 patients (60%) received concomitant methotrexate (15 (10–20) mg/wk). Baseline IFX dose was 3.1 (3.0–4.8) mg/kg every 7 (6–9) weeks. At baseline, 60% of pts had low sIFX and 29% very low and at follow-up it was 57% and 29%, respectively. At baseline, 14 pts (15%) had medium-high ADA, at follow up 16%. Median sIFX was lower at baseline vs. follow-up (1.8 (0.8–5.8) vs 2.4 (0.8–6.2) mg/l, p=0.006) whereas ADA were similar (p=0.7). Six of 58 pts with low baseline sIFX had high sIFX at follow-up, and 3 of 38 pts with high baseline sIFX had low sIFX at follow-up. Similar numbers for low vs. medium–high ADA at baseline and follow-up were 2/81 and 3/15. For the rest, sIFX and ADA remained stable between baseline and follow-up in 87/96 (91%) and 91/96 (95%), respectively (Figure). MTX use was not associated with sIFX or ADA (both p>0.05). Patients with low sIFX received lower IFX doses than pts with sIFX ≥3mg/l (255 (200–320) mg vs. 300 (250–400) mg, p=0.02) and with longer intervals (8 (6–10) weeks vs. 6 (6–6)weeks, p 0.05). Conclusions In this highly selected group of patients treated with originator infliximab for >5 years, non-medical switch to biosimilar IFX had no negative impact on sIFX or ADA 2–4 months following switch. At baseline, 60% of patients had low sIFX but few patients had ADA, perhaps indicating low immunogenicity in these patients. Disclosure of Interest None declared

OBJECTIVE: Because the criteria used for diagnosing between generalized joint hypermobility (GJH) and musculoskeletal complaints, as well as relations between GJH and an insufficient motor development and/or a reduced physical activity level differ, the prevalence of GJH varies considerably. The aim of this study was to survey the prevalence of GJH defined by a Beighton score at ≥4, ≥5, or ≥6 positive tests of 9 and benign joint hypermobility syndrome (BJHS) in Danish primary school children at 8 years of age. A second aim was to compare children with and without GJH and BJHS regarding motor competence, self-reported physical activity, and incidence of musculoskeletal pain and injuries. METHODS: A cross-sectional study of 524 children in the second grade from 10 public schools was performed. A positive response rate was obtained for 416 (79.4%) children, and 411 (78.4%) children were clinically examined and tested for motor competence, whereas questionnaire response to items comprising musculoskeletal pain and injuries, in addition to daily level and duration of physical activity, corresponded to 377 (71.9%) children. RESULTS: In total, 29% of the children had GJH4, 19% had GJH5, 10% had GJH6, and 9% had BJHS, with no gender difference. There was no difference in daily level and duration of physical activity and in frequency of musculoskeletal pain and injuries between those with and without GJH. Children with ≥GJH5 as well as with ≥GJH6 performed better in the motor competence tests. CONCLUSION: Motor competence and physical activity are not reduced in primary school children at 8 years of age with GJH or BJHS. It is recommended that a potential negative influence on the musculoskeletal system over time, as a result of GJH, be investigated by longitudinal studies.

To test the reproducibility of tests and criteria for generalized joint hypermobility (GJH) and benign joint hypermobility syndrome (BJHS).A standardized protocol for clinical reproducibility studies was followed using a three-phase study (with a training, an overall agreement and a test phase). An overall agreement of at least 0.80 was required to proceed to the test phase. Phases 1, 2 and 3 used 14 patients (with varying degrees of hypermobility), 20 patients (50% cases) and 40 patients (50% cases), respectively. The inclusion criterion for cases was hypermobility (patients with Ehlers-Danlos Syndrome or BJHS) and for controls, non-hypermobility (patients with shoulder and/or back pain); patients were selected from patients' files (phases 1 and 2) or included consecutively from our outpatient clinic (phase 3).The overall agreement in phase 2 was 0.95 for GJH and 0.90 for BJHS. Reproducibility for diagnosing GJH and BJHS in phase 3 showed kappa values of 0.74 and 0.84, respectively. Kappa in the Beighton tests for diagnosing GJH (currently or historically) was generally above 0.80, except for the fifth fingers and elbows (or = 0.60). In the Brighton tests for diagnosing BJHS, kappa was above 0.73, except for the skin signs (0.63). Lowest kappa was found in the Rotès-Quérol tests, where it wasor = 0.57, except for the right shoulder (0.31).We found a good-to-excellent reproducibility of tests and criteria for GJH and BJHS. Future research on the validity of the tests and criteria for joint hypermobility is urgently needed.

Background Rheumatoid arthritis (RA) is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) is measured by Digital X-ray Radiogrammetry (DXR) which has been proposed as an outcome measure for treatment effect in RA. A definition of increased HBL adjusted for age- and gender-related bone loss is lacking. Furthermore, it is unknown to which extent HBL is normalised in RA patients during treatment with tumour necrosis factor alpha inhibitors (TNF-I). Objectives To establish a reference material for HBL and to investigate whether HBL normalises in RA patients during TNF-I treatment in clinical practice. Methods Hand bone mass (DXR-BMD) was measured with DXR, a computerised method of estimating cortical bone mineral density in the diaphysis of the 2nd – 4th metacarpal bone in a reference population and a patient cohort. The reference population consisted of 1,533 men and 2618 women randomly selected from the urban county of Osterbro in Denmark who had hand x-rays performed in the cross-sectional Copenhagen Osteoarthritis Study. Linear regression analyses were used to calculate normal HBL (defined as the 95% Confidence Interval (95%CI) for the age-related mean changes in DXR-BMD between subsequent age-groups). The patient cohort was 135 patients from the DANBIO registry with hand x-rays obtained ∼2 years before start of TNF-I (pre-baseline, all patients treated with conventional synthethic Disease-Modifying Anti-Rheumatic Drugs (csDMARD)), at start of TNF-I (baseline) and ∼ 2 years after start of TNF-I (follow-up). Annual HBL during csDMARD and TNF-I treatment were calculated in individual patients and compared with the lower 95%CI of mean DXR-BMD change in the gender- and age-matched reference group to assess if increased HBL was present. Results [Table 1][1] presents the HBL reference material. The 135 RA patients (85% women, 71% IgM-RF positive, median age 55 (range 23-84) years; median disease duration 5 (range 1-53) years) had a pre-baseline median DAS28 of 4.3 (range 1.6-6.9) and a baseline DAS28 of 5.3 (1.4-8.2). TNF-I treatment was infliximab (74%), etanercept (13%) or adalimumab (13%). At follow-up (DAS28 3.1 (1.4-7.7) 59% received the initial TNF-I, 27% had switched to another biological drug and 14% had withdrawn. Compared to the reference population, 84 (62%) patients had increased HBL during csDMARD treatment and 60 (44%) had during TNF-I treatment (p=0.10,Chi-Sq). In 42 patients who had elevated HBL during csDMARD treatment HBL was normalised during TNF-I. Eighteen patients had normal HBL during csDMARD treatment but increased HBL during treatment with TNF-I. ![Figure][2] Conclusions We have established a reference material for HBL in the general population and found significant age-related decreases in DXR-BMD in both men and women. Increased HBL was present in the majority of RA patients initiating TNF-I treatment in clinical practice and was normalised in only a minority of patients during treatment. Disclosure of Interest None declared [1]: #F1 [2]: pending:yes

Background. We have developed the Major Depression Inventory (MDI), consisting of 10 items, covering the DSM-IV as well as the ICD-10 symptoms of depressive illness. We aimed to evaluate this as a scale measuring severity of depressive states with reference to both internal and external validity.Method. Patients representing the score range from no depression to marked depression on the Hamilton Depression Scale (HAM-D) completed the MDI. Both classical and modern psychometric methods were applied for the evaluation of validity, including the Rasch analysis.Results. In total, 91 patients were included. The results showed that the MDI had an adequate internal validity in being a unidimensional scale (the total score an appropriate or sufficient statistic). The external validity of the MDI was also confirmed as the total score of the MDI correlated significantly with the HAM-D (Pearson's coefficient 0·86, P[les ]0·01, Spearman 0·80, P[les ]0·01).Conclusion. When used in a sample of patients with different states of depression the MDI has an adequate internal and external validity.

Background Concurrent use of methotrexate (MTX) and a biologic is generally the standard-of-care in patients with RA who have disease activity despite MTX. It has been estimated that between 10 and 30% of RA patients are MTX-intolerant (1). For patients who are prescribed treatment with a biologic agent and not tolerating MTX, biological monotherapy may be considered. From DANBIO it has been estimated that 19% of RA patients in Denmark are in biologic monotherapy (2). Objectives To elucidate the effectiveness (CDAI remission rates) and drug adherence of bDMARD therapies prescribed as monotherapy in Danish RA patients. Methods All RA patients, treated with bDMARDs registered in DANBIO as initiating bDMARD as monotherapy, i.e. without concomitant conventional synthetic DMARDs (csDMARDs), from May 1 2011 to April 30 2013, were eligible for inclusion (2). Descriptive statistics for effectiveness and drug adherence of bDMARD monotherapy were calculated. Results 775 patients were included (77% women, disease duration (mean [SD]): 12.6 [10.8], age: 56.0 years [12.9], 71% IgM-RF positive, CDAI: 21.1 [14.5], and DAS28: 4.4 [1.6]. At 6 months follow-up CDAI remission rates were principally separated into two clusters; a group with “poor” (0-10%) remission rates (consisting of abatacept [0/11], certolizumab [1/10] and infliximab [2/32]), and a group with “good” (above 20%) remission rates (adalimumab [35/124], etanercept [46/215], golimumab [4/16] and tocilizumab [23/86]), with rituximab in between [15%; 10/69]) (Figure). Overall, DAS28 remission was achieved in 41% (242/587), with similar pattern of remission between drugs as CDAI remission rates. With the exception of patients treated with infliximab (14%) and rituximab (16%), around one third of the patients achieved an ACR50 response (105/339). After 2 years of monotherapy, the proportion of patients still on drug was more than two thirds, when excluding infliximab. As illustrated in the figure the drug adherence rate was apparently highest for etanercept and adalimumab, and in a post hoc analysis, infliximab had significantly poorer drug adherence when compared to all the other bDMARDs (p Conclusions At 6 months9 follow-up a “poor” remission rate group (abatacept, certolizumab and infliximab), and a “good” remission rate group (adalimumab, etanercept, golimumab and tocilizumab), with rituximab in between, were found in patients with RA treated with biologics in monotherapy in routine care. References Yazici Y, Shi N, John A. Utilization of biologic agents in rheumatoid arthritis in the United States: analysis of prescribing patterns in 16,752 newly diagnosed patients and patients new to biologic therapy. Bull NYU Hosp Jt Dis 2008;66(2):77-85. Jorgensen T.S. et al.The Prevalence of Biological Monotherapy among Rheumatoid Arthritis Patients (RA) in Denmark: Results from the Danish Nationwide DANBIO Registry. ACR congress 2013, poster no. 1478 Acknowledgements This study was supported by the Oak Foundation and Roche Denmark. Disclosure of Interest T. Jorgensen: None declared, L. Kristensen Consultant for: AbbVie, BMS, MSD and Pfizer, R. Christensen: None declared, H. Bliddal Grant/research support: Abbvie, Roche, Pfizer, and NOVO, Consultant for: Roche, Pfizer and BMS, T. Lorenzen Consultant for: Advisory Board member Roche and Pfizer, M. Hansen Consultant for: AbbVie and Roche, M. Ostergaard Grant/research support: Abbott, Bristol- Myers Squibb, Centocor, GlaxoSmithKline, Janssen, Merck, Mundipharma, Novo Nordisk, Pfizer, Schering-Plough, Roche UCB, and Wyeth, Consultant for: Abbott, Bristol- Myers Squibb, Centocor, GlaxoSmithKline, Janssen, Merck, Mundipharma, Novo Nordisk, Pfizer, Schering-Plough, Roche UCB, and Wyeth, J. Jensen: None declared, L. Zanjani: None declared, T. Laursen: None declared, S. Butt: None declared, M. Dam: None declared, H. Lindegaard Consultant for: Lilly, MSD, Nordpharma and Roche, J. Espesen: None declared, O. Hendricks: None declared, P. Kumar: None declared, A. Kincses: None declared, L. Larsen: None declared, M. Andersen: None declared, E. Naeser: None declared, D. Jensen: None declared, J. Grydehoj: None declared, B. Unger: None declared, N. Dufour: None declared, V. Sorensen: None declared, S. Vildhoj: None declared, I. Hansen Consultant for: Roche, Pfizer og MSD, J. Raun: None declared, N. Krogh: None declared, M. Hetland Grant/research support: Pfizer, ROche og MSD DOI 10.1136/annrheumdis-2014-eular.3651

With this study, we wanted to determine the incidence of symptom-giving pelvic girdle relaxation during pregnancy and the prevalence post partum, identify predisposing factors, and determine the frequency of sick leave. A total of 1600 pregnant women entered the study. The incidence during pregnancy was 14%, the prevalence two, six, and twelve months post partum was 5%, 4%, and 2%, respectively. Multivariate analysis indicated that the most important predisposing factor was pelvic pain in a previous pregnancy. Other factors were uncomfortable working conditions, lack of exercise, and previous low back and low abdominal pain. At least 37% of the women with symptom-giving pelvic girdle relaxation were on sick leave during pregnancy, on average for twelve weeks. Symptom-giving pelvic girdle relaxation is a considerable problem both in pregnancy and post partum. The occupational risk can possibly be prevented. The syndrome has a great social impact because of the high frequency of sick live.

Pelvic pain in pregnancy appears to be a problem on the increase. This study was undertaken to describe and analyse the relationship between subjective symptoms, daily disability, and clinical findings in women with symptom-giving pelvic girdle relaxation in pregnancy. Out of 1600 pregnant women, 238 had pelvic pain. After a clinical examination 11 women were excluded due to low back pain. The rest, 227 women, was considered to have symptom-giving pelvic girdle relaxation during pregnancy. Symptom-giving pelvic girdle relaxation in pregnancy seriously interferes with many activities of daily living such as housekeeping, walking, working, and sexual life. The women's statements of pelvic pain are well correlated to the number of positive clinical tests. Symptom-giving pelvic girdle relaxation in pregnancy causes considerable disabilities concerning daily activities.

BACKGROUND: The pregnancy associated hormone relaxin induces loosening of the pelvic ligaments in several species. This study was undertaken to evaluate whether pregnant women with symptom-giving girdle relaxation had increased serum relaxin concentrations during pregnancy.METHOD: Serum relaxin concentrations were measured in 38 pregnant women with symptom-giving pelvic girdle relaxation at the time of diagnosis, in the 30th and 38th week of pregnancy as well as 2 and 6 months after delivery. Fourteen pregnant women without symptoms served as a control group. Relaxin concentrations were measured by a homologous enzyme linked immuno-sorbent assay. All participants were clinically examined including tests for symptom-giving pelvic girdle relaxation.RESULTS: No differences in serum relaxin concentrations were found throughout pregnancy and after delivery.CONCLUSION: The present results do not suggest an important role for relaxin in symptom-giving pelvic girdle relaxation during human pregnancy.

The changes of concentrations of prostaglandins (PG) are cyclic in the uterine tissues and related to steroid ovarian hormones. The role in normal menstruation is presumably related to a local haemodynamic effect. PGF2 alpha vasoconstricts the endometrial vessels during menstruation and contracts the smooth muscle of the myometrium. PGE2 vasodilates the vessels of the endometrium, and PGI2 relaxes smooth muscle, vasodilates the vessels of the myometrium and inhibits thrombocyte aggregation. The pathological conditions dysmenorrhea and menorrhagia relates to symptoms which seem to be exaggerations of normal activities, probably due to increased PG levels. Prostaglandin synthesis inhibitors (PGSI) in women have not been able to prevent ovulation, but animal experiments have shown that the bursting of the follicle demands prostaglandins. In vitro experiments with human tissue have shown that PG is necessary for the occurrence of dissociation of connective tissue around the apex. Luteolysis is due to PG in several species, but it has not been possible to find this direct effect of PG upon luteolysis in women. However, there are indications that the PG functions as a mediator for or is mediated by catecholamines and/or oxytocin.

Hearing sensitivity was measured for tones from 1,000 through 8,000 hertz (Hz) in 534 males and 278 females who resided in rural Wisconsin and ranged in age from 16 to 85 years. The hearing sensitivity for all subjects decreased with advancing age and at higher frequencies, but hearing loss over the range most susceptible to excessive noise exposure (3,000-6,000 Hz) was much greater for males than for females at all ages. The hearing loss was greater than could be accounted for by age and was similar whether the subject was a farmer or not. The results suggested that approximately 25 percent of the males had a communication handicap due to hearing loss by age 30, and the proportion rose to 50 percent by age 50. Less than 20 percent of farmers reported consistent use of personal hearing protection in their farm-related duties. Overall, the findings suggest that men who live in rural areas, including farmers, demonstrate a high prevalence of hearing loss and associated communication problems due to excessive noise exposure. This, in turn, clearly indicates a need for intensification of educational hearing conservation programs for the rural population.

The effect of early antihypertensive treatment on survival of patients with diabetic nephropathy was evaluated by studying two cohorts of Type 1 (insulin-dependent) diabetic patients developing persistent proteinuria in I: 1957-1973 (late treatment group n = 49) and II: 1979-1983 (early treatment group n = 71). At onset of nephropathy, the two cohorts were comparable with regard to age (29(8) vs 30(8) years, mean (SD], duration of diabetes (16(6) vs 18(7) years), blood pressure (132(16)/85(11) vs 134(16)/86(8) mm Hg), proteinuria (0.8(0.5-1.2) vs 0.8(0.6-1.2) g x 24 h-1, median (quartiles] and serum creatinine (87(14) vs (85(16) mumol x 1(-1]. The patients were followed frequently at the outpatients' clinic until death or for a median duration of 8 years. In the first cohort antihypertensive treatment was seldom used, whereas, in the second cohort antihypertensive treatment was started when blood pressure reached 144(18)/93(7) mm Hg. The probability of survival with a functioning kidney for more than 8 years was 48% in the first cohort and 87% in the second cohort, p less than 0.001. The improvement of survival was due mainly to a decreased mortality from uraemia. Early antihypertensive treatment is the most likely explanation for this improvement.