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Background: We aimed to describe the uptake of newer biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in psoriatic arthritis (PsA) in the Nordic countries and to compare their retention and effectiveness.Methods: Patients with PsA starting a b/tsDMARD in 2012-2020 in five Nordic rheumatology registers were included. Uptake and patient characteristics were described, with comorbidities identified from linkages to national patient registries. One-year retention and 6-month effectiveness (proportions achieving low disease activity (LDA) on the Disease Activity Index for PSoriatic Arthritis based on 28-joint evaluation) for the newer b/tsDMARDs (abatacept/apremilast/ixekizumab/secukinumab/tofacitinib/ustekinumab) were compared with adalimumab through adjusted regression models stratified by treatment course (first, second/third, and fourth or more).Results: In total, 5659 treatment courses with adalimumab (56% biologic-naïve) and 4767 courses with a newer b/tsDMARD (21% biologic-naïve) were included. The uptake of newer b/tsDMARDs increased from 2014 and plateaued in 2018. Patient characteristics appeared similar across treatments at treatment start. Adalimumab was more often used as the first course and newer b/tsDMARDs more often in biologic-experienced patients. Used as a second/third b/tsDMARD, the retention rate and the proportion achieving LDA were significantly better for adalimumab (rate 65%, proportion 59%) compared with abatacept (45%, 37%), apremilast (43%, 35%), ixekizumab (LDA only, 40%) and ustekinumab (LDA only, 40%), but not significantly different from other b/tsDMARDs.Conclusion: Uptake of newer b/tsDMARDs occurred mainly in biologic-experienced patients. Regardless of mode of action, only a minority of patients starting a second or later b/tsDMARD course remained on drug and achieved LDA. Superior outcomes for adalimumab indicate that the positioning of newer b/tsDMARDs in the PsA treatment algorithm remains to be established. Background: We aimed to describe the uptake of newer biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in psoriatic arthritis (PsA) in the Nordic countries and to compare their retention and effectiveness. Methods: Patients with PsA starting a b/tsDMARD in 2012-2020 in five Nordic rheumatology registers were included. Uptake and patient characteristics were described, with comorbidities identified from linkages to national patient registries. One-year retention and 6-month effectiveness (proportions achieving low disease activity (LDA) on the Disease Activity Index for PSoriatic Arthritis based on 28-joint evaluation) for the newer b/tsDMARDs (abatacept/apremilast/ixekizumab/secukinumab/tofacitinib/ustekinumab) were compared with adalimumab through adjusted regression models stratified by treatment course (first, second/third, and fourth or more). Results: In total, 5659 treatment courses with adalimumab (56% biologic-naïve) and 4767 courses with a newer b/tsDMARD (21% biologic-naïve) were included. The uptake of newer b/tsDMARDs increased from 2014 and plateaued in 2018. Patient characteristics appeared similar across treatments at treatment start. Adalimumab was more often used as the first course and newer b/tsDMARDs more often in biologic-experienced patients. Used as a second/third b/tsDMARD, the retention rate and the proportion achieving LDA were significantly better for adalimumab (rate 65%, proportion 59%) compared with abatacept (45%, 37%), apremilast (43%, 35%), ixekizumab (LDA only, 40%) and ustekinumab (LDA only, 40%), but not significantly different from other b/tsDMARDs. Conclusion: Uptake of newer b/tsDMARDs occurred mainly in biologic-experienced patients. Regardless of mode of action, only a minority of patients starting a second or later b/tsDMARD course remained on drug and achieved LDA. Superior outcomes for adalimumab indicate that the positioning of newer b/tsDMARDs in the PsA treatment algorithm remains to be established.

Background/Aims In axial spondyloarthritis, it has been shown that while some adverse lifestyle factors (smoking and high body mass index (BMI)) are less likely to respond to TNF inhibition (TNFi), those who drink alcohol are more likely to respond to treatment - a result currently unexplained, and unlikely to be causal. We aimed to investigate these associations in psoriatic arthritis (PsA) and to quantify the impact of lifestyle factors on TNFi treatment response. Methods Adults with PsA commencing TNFi were identified via the European Spondyloarthritis Research Collaboration Network (https://eurospa.eu). Participants were required to have data on lifestyle factors (smoking, alcohol consumption, and/or BMI) recorded within ±30 days of commencing TNFi. The relationship between lifestyle factors and treatment outcome (ACR-50 response criteria at 12 months) was assessed using logistic regression, adjusted for age, sex, country, year of TNFi initiation, disease duration and baseline disease activity (DAS28). The analysis was then repeated for other treatment response criteria: ACR-20, ACR-70, DAPSA28-remission, DAPSA68-remission and Minimal Disease Activity. Results From 12 PsA registries, 9409 participants were included, 21% of whom were current smokers, 54% drank alcohol, 38% were overweight and 29% were obese. Other baseline characteristics are shown in Table 1. Among smokers, 18% met ACR-50 response criteria at 12 months, versus 26% of non-smokers, an association that remained after adjusting for potential confounders (adjusted odds ratio: 0.59; 95%CI: 0.48-0.72). Participants who were overweight (adjusted odds ratio: 0.80; 0.64-0.99) or obese (0.57; 0.44-0.72) were also less likely to achieve treatment response, compared to patients of normal weight. Similar results were seen across other outcome measures. The proportion who achieved ACR-50 response did not differ between patients who did/did not consume alcohol (both 22%). Conclusion Smoking and high BMI were associated with substantial decreases in the likelihood of TNFi response. The addition of non-pharmacological therapy, including the modification of adverse lifestyle factors, may offer the potential to enhance treatment outcomes. For example, if 100 patients were able to give up smoking when commencing TNFi, an additional eight would achieve ACR-50 at 12 months. Previous findings regarding alcohol and treatment response in axSpA were not replicated in PsA. Disclosure G.T. Jones: None. O. Rotariu: None. B. Michelsen: None. B. Glintborg: None. B. Gudbjornsson: None. T.J. Love: None. D. Nordström: None. T. Sokka: None. J. Vencovský: None. P. Horák: None. Z. Rotar: None. M. Tomšič: None. M. van der Sande: None. M.J. Nissen: None. B. Möller: None. C. Codreanu: None. J.K. Wallman: None. K.M. Fagerli: None. S.H. Rasmussen: None. L.M. Ørnbjerg: None. M.J. Santos: None. P. Carvalho: None. M.L. Hetland: None. M. Østergaard: None. G.J. Macfarlane: None.

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Objectives To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment. Methods Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999–2008), B (2009–2014) and C (2015–2018). Retention, remission and response rates were assessed at 6, 12 and 24 months. Results In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months. Conclusion Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.

Objectives To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006–18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. Results We found increased aOR of PTB [1.92 (1.56–2.35)] and SGA [1.93 (1.45–2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs Conclusion During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment.

To investigate the distribution of patient-reported outcomes (PROs) in axial spondyloarthritis (axSpA) patients initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the New York criteria for ankylosing spondylitis (AS) versus non-radiographic axSpA (nr-axSpA) patients.Fifteen European registries contributed PRO scores for pain, fatigue, patient global, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) from 19,498 axSpA patients. Changes in PROs and PRO "remission" rates (definitions: ≤20 mm for pain, fatigue, patient global, BASDAI and BASFI; ≤0.5 for HAQ) were calculated at 6, 12 and 24 months of treatment.Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, six months after start of a 1st TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25), patient global (66/29/21/20), BASDAI (58/26/21/19), BASFI (46/20/16/16) and HAQ (0.8/0.4/0.2/0.2). Patients with AS, n=3281 had a slightly better response than nr-axSpA patients, n=993. LUNDEX-adjusted "remission" rates at 6 months for pain/fatigue/patient global/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the non-radiographic axSpA cohort. Better PRO responses were seen with a 1st TNFi compared to 2nd and 3rd TNFi.AxSpA patients starting a TNFi achieved high PRO "remission" rates, most pronounced in those fulfilling the modified New York criteria and for the first TNFi.

ObjectiveSeveral advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA.MethodsWe updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.ResultsThe number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab.ConclusionWe have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

ObjectivesTo evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi).MethodsWe identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naïve PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naïve PsA patients and versus the general population adjusted for age, sex, calendar period and country.ResultsDuring 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68–1.35) versus biologics-naïve PsA from CRR and an IRR of 0.84 (0.64–1.10) versus biologics-naïve PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17–1.55). The estimates were largely similar for lymphoid and myeloid malignancies.ConclusionsTreatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.

Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97–0.98), men vs. women: 1.88 (1.60–2.22), current vs. non-smoking: 0.76 (0.63–0.91), HLA-B27 positive vs. negative: 1.51 (1.20–1.91), TNF start year 2015–2018 vs. 2009–2014: 1.24 (1.06–1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectively Conclusion: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.

Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009–2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3, ≥4 or ≥5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009–2011, 2012–2013, 2014–2015, 2016–2018). In the subgroup of patients starting a first b/tsDMARD 2009–2015, baseline characteristics associated with multi-switching (within 3 years’ follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009–2015, whereof proportions treated with ≥3, ≥4 or ≥5 b/tsDMARDs within 3 years’ follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/., Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

ObjectiveThe associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients the cross-sectional and longitudinal relation of fatigue with subjective as well as objective assessments of disease activity.MethodsRA patients were consecutively included when initiating biologic disease-modifying anti-rheumatic drugs (DMARDs) and assessed at baseline, 1, 2, 3, 6, and 12 months with investigation of fatigue, patient-reported outcome measures (PROMs; joint pain and patient’s global disease activity, MHAQ, pain catastrophizing, Mental Health score), clinical examinations (examiner’s global disease activity, 28 tender and swollen joint counts), and laboratory variables (ESR, CRP, calprotectin). Ultrasound examinations (semi-quantitative scoring (0–3)) with grey scale and power Doppler were performed of 36 joints and 4 tendons. Statistics included one-way analysis of variance, Pearson’s correlations, and multiple linear and logistic regression analysis.ResultsA total of 208 RA patients (mean (SD) age 53.2 (13.2) years, disease duration 9.8 (8.5) years) were included. Fatigue levels diminished during follow-up (mean (SD) baseline/12 months; 4.8 (2.8)/3.0 (2.5) (p< 0.001)). Substantial correlations were cross-sectionally found between fatigue and PROMs (median (IQR) r=0.61 (0.52-0.71)) but not with the objective inflammatory assessments. During follow-up, baseline fatigue was associated with PROMs (p< 0.001) but not with objective inflammatory assessments. However, change of fatigue was associated with change in all variables. Higher baseline fatigue levels were associated with lower clinical composite score remission rates.ConclusionFatigue was cross-sectionally associated to subjective but not to objective disease assessments. However, change of fatigue during treatment was associated to all assessments of disease activity.Trial registration numberAnzctr.org.auidentifier ACTRN12610000284066, Norwegian Regional Committee for Medical and Health Research Ethics South East reference number 2009/1254Key Points•In this longitudinal study of patients with established RA, fatigue was associated with patient reported outcome measures at each visit, but not with objective assessments of inflammation including calprotectin and comprehensive ultrasound examinations.•Changes in fatigue during biological treatment were associated with changes in patient reported outcome measures, clinical, laboratory and ultrasound assessments.•Baseline fatigue was associated with all patient reported outcome measures, but not objective assessments of inflammation at all the prospective visits.•Higher baseline fatigue levels were associated with lower remission rates as assessed by clinical composite scores.

We aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive.TNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay. Comparisons between nADAb-positive and -negative patients were done in unadjusted analyses as well as in adjusted logistic regression and general linear models.A total of 282 patients with IA currently under treatment with TNFi were included. nADAb were identified in 11 patients (nine treated with infliximab, one with etanercept and one with certolizumab pegol). Patients with nADAb reported significantly worse joint pain, patient's global assessment, Health Assessment Questionnaire, Bath Ankylosing Spondylitis Disease Activity/Functional Index and Short-Form-36 physical functioning scale score than patients without nADAb (p 0.04, adjusted analyses). 28-joint Disease Activity Score, Simplified Disease Activity Index and Maastricht Ankylosing Spondylitis Enthesitis score were also significantly worse in the nADAb-positive patients (p 0.04, adjusted analyses), as were serum calprotectin, C-reactive protein and numbers of circulating peripheral leukocytes (p ≤ 0.001). A significantly higher proportion of nADAb-positive patients were current smokers (46 vs. 15%), in unadjusted as well as adjusted analyses (p ≤ 0.008).nADAb-positive patients were more frequently smokers and had significantly worse disease activity, physical function, and inflammatory markers, than patients without nADAb. The association between smoking and nADAb positivity warrants further examination.

Objectives Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. Methods Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP Results Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P Conclusion This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.

Objectives To investigate whether patient-reported outcomes vary across countries and are influenced by cultural/contextual factors. Specifically, we aimed to assess inter-country differences in tender joint count (TJC), pain and patient’s global health assessment (PGA), and their impact on disease activity (DAS28-CRP) in RA patients from five Nordic countries. Methods We collected data (baseline, 3- and 12-months) from rheumatology registers in the five countries comprising RA patients starting a first ever MTX or a first ever TNF inhibitor (TNFi). In order to assess the role of context (=country), we separately modelled TJC, pain and PGA as functions of objective variables (CRP, swollen joint count, age, sex, calendar period and disease duration) with linear models. Analyses were performed at each time point and for both treatments. We further assessed the impact of inter-country differences on DAS28-CRP. Results A total of 27 645 RA patients started MTX and 19 733 started a TNFi. Crude inter-country differences at MTX start amounted to up to 4 points (28 points scale) for TJC, 10 and 27 points (0–100 scale) for pain and PGA, respectively. Corresponding numbers at TNFi start were 3 (TJC), 27 (pain) and 24 (PGA) points. All differences were reduced at 3- and 12-months, and attenuated when adjusting for the objective variables. The variation in predicted DAS28-CRP across countries amounted to Conclusions Inter-country differences in TJC, pain and PGA are greater than expected based on differences in objective measures, but have a small clinical impact on DAS28-CRP across countries.

Objective: To examine the prevalence of self-reported problems with sexual activity among psoriatic arthritis (PsA) patients, and to explore potential associations of such problems with various demographic, musculoskeletal, and dermatological disease variables. Method: Consecutive PsA patients were recruited from an outpatient clinic. Data collected included demographics, measures of musculoskeletal and skin disease activity, and treatments. Perceived effect of health status on sexual activity was assessed using question number 15 from the health-related quality of life instrument 15D; this was explored in univariate and multivariate logistic regression analyses. Results: The study assessed 135 patients (mean age 52.1 years, disease duration 8.7 years, 51.1% male). Mean scores included Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 2.9, Disease Activity index for PSoriatic Arthritis (DAPSA) 18.2, patient global assessment (PGA) 36.0 mm, pain 33.7 mm, fatigue 45.1 mm, modified Health Assessment Questionnaire (mHAQ) 0.42, Psoriasis Area Severity Index (PASI) 2.5, and Dermatology Life Quality Index (DLQI) 3.4. Twenty-four patients (17.8%) reported that their health status had a large negative effect and 111 (82.2%) that it had no or little effect on their sexual activity. In univariate analyses, a statistically significant association with impaired sexual activity was found for longer disease duration and higher MASES, DAPSA, PGA, fatigue, and mHAQ scores, but not for demographic variables or variables reflecting skin psoriasis involvement (PASI, DLQI). In adjusted analyses, only PsA disease duration remained independently associated with impaired sexual activity. Conclusion: One in five PsA patients perceived that their health status had a negative impact on sexual activity. Disease duration and measures reflecting musculoskeletal involvement, but not measures reflecting skin psoriasis involvement, appeared to be associated with impaired sexual activity.

IMPORTANCE: Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. OBJECTIVE: To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. DESIGN, SETTING, AND PARTICIPANTS: Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. INTERVENTIONS: Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). MAIN OUTCOME AND MEASURES: The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. RESULTS: Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P

ObjectivesTo compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.MethodsObservational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008–2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.Results24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.ConclusionThe rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.

ObjectiveTo investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA).MethodsFifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment.ResultsHeterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/ 6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi.ConclusionPatients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

ObjectivesJoint swelling and tenderness are considered a proxy for inflammation in patients with rheumatoid arthritis (RA). With ultrasound-detected inflammation as reference, our objectives were to explore on patient and joint level the associations between ultrasound synovitis and joint swelling, tenderness and patient-reported joint pain (PRJP).Methods209 patients with established RA were examined six times during 12 months with assessment of 32 joints in upper/lower extremities for joint swelling/tenderness and Grey scale (GS)/power Doppler (PD) synovitis. PRJP was assessed on a manikin. Correlations between different sum scores were at each examination calculated using Spearman’s rho (r), agreement at joint level was examined by Cohen’s kappa and logistic regression models were used to explore the associations between joint assessment and GS/PD scores.ResultsAt patient level, swollen joints were strongly correlated with GS/PD sum scores (r=0.64–0.88), while tender joints were primarily associated with PRJP (r=0.54–0.68). At joint level, GS/PD pathology had higher agreement with swelling (kappa 0.54–0.57) than tenderness (kappa 0.20–0.21) or PRJP (0.23–0.25). Higher percentages of joints were swollen according to increasing GS/PD scores, independently of joint tenderness. However, joints being tender, but not swollen, were not associated with GS/PD scores. Receiver operating curves showed swollen but not tender joints to be associated with GS/PD scores.ConclusionsSwollen joints were strongly associated with ultrasound detected synovitis at both patient and joint level, while this association was not found for tender joints. These results may question if tender joints reflect ongoing inflammation in established RA.

Importance Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear. Objective To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. Design, Setting, and Participants Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019. Interventions Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204). Main Outcomes and Measures The primary end point was clinical remission at week 30. Results Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, −8.2% to 11.1%;P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively. Conclusions and Relevance Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates. Trial Registration ClinicalTrials.gov Identifier:NCT03074656

Contains fulltext : 251829.pdf (Publisher’s version ) (Open Access) OBJECTIVE: There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. METHODS: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. RESULTS: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (4 years), and varied significantly across the European registries. CONCLUSION: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.

Objective: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. Methods: This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015–2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score adj 1.43 [95% CI 1.12–1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score

Background:Rheumatoid Arthritis (RA) is associated with increased cardiovascular co-morbidity including acute coronary syndrome (ACS), partly due to effects of systemic inflammation. Disease-modifying anti-rheumatic drugs (DMARDs) may reduce RA disease activity, but act through several pathways and may themselves have an impact on cardiovascular risks. Whether the risks of ACS associated with biologic (b) and targeted synthetic (ts) DMARDs differ is still unknown.Objectives:To assess and compare incidences of ACS during treatment of RA with etanercept (ETA), adalimumab (ADA), infliximab (INF), certolizumab pegol (CTZ), golimumab (GOL), rituximab (RIT), abatacept (ABA), tocilizumab (TCZ), baricitinib (BAR) or tofacitinib (TOF).Methods:We defined and pooled treatment cohorts of patients starting any of the above treatments between 2008 and 2017 from clinical rheumatology registers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE). One patient could contribute several treatment episodes. Age, sex, co-medication (methotrexate, prednisolone), number of previous b/tsDMARDs, CRP, comorbidities (cardiovascular (including ACS (defined as ICD-10: I20.0, I21.0-4, I21.9) and cerebrovascular disease, thromboembolic events, diabetes, hospitalized infection, cancer, kidney failure, COPD) and associated drugs were extracted and used as adjustment in Cox regression analyses comparing the incidence of ACS between treatments. We used several follow-up lengths (1, 2, and up to 5 years) and two different risk windows (ACS on drug [ending follow-up on treatment discontinuation] and ACS ever since treatment start [disregarding any treatment discontinuation]). We also stratified by age and number of previous b/tsDMARDs.Results:We included 40850 treatment courses in 24083 patients (DK 7271, FI 3732, NO 1540, and SE 11540; around 75% women). ETA was the most common treatment (27%) whereas BAR and TOF comprised We found 780 incident ACS events during 141 326 person-years (pyrs) in the 5-year follow-up time and “ACS ever since treatment start” risk window, resulting in a crude incidence rate of 5.5 events per 1000 pyrs. No event was recorded for BAR nor TOF, which also had the shortest follow-up. Adjusted hazard ratios (HR) increased slightly with longer follow-up times, but the two risk windows provided similar HRs. For the 5-year follow-up, RIT was associated with an increased risk of ACS compared to ETA (Table), while no association was observed for shorter follow-up times. Stratifying on age did not modify the associations. Separate analyses by number of previous b/tsDMARDs suggested that ABA (HR=1.8, 95% CI 1.0-3.3), INF (HR=2.2, 95% CI 1.0-4.6) and RIT (HR=1.9, 95% CI 1.1-3.4) were associated with increased risks of ACS compared to ETA in the subgroup of patients with two or more previous bDMARDs (Figure), whereas no differences were found among patients starting either drug as 1st/2nd bDMARD.Table 1.Comparisons of risks for ACS during a 5-year follow-up since start of bDMARD treatment.DrugN eventspyrsCrude incidence rate/ 1000 pyrsHR (95% CI)1ETA175359174.9ref.ADA115240934.81.0 (0.8-1.3)CTZ54141583.80.9 (0.6-1.2)GOL4090064.41.1 (0.8-1.5)INF106178036.01.2 (0.9-1.5)ABA70107956.51.1 (0.8-1.4)RIT158166229.51.3 (1.0-1.6)TCZ62128664.80.9 (0.5-1.2)BAR036TOF030Pyrs: person-years; HR: hazards ratio1 adjustment: see text.Conclusion:In this cohort including ≥ 24,000 patients followed for up to 5 years, the ACS incidence rate was 5.5/1000 pyrs, with RIT showing an increased risk compared to ETA. In clinical practice, the choice of bDMARD does not seem to influence ACS risk in the short term. In the longer term, differences in ACS risk between bDMARDs may reflect channeling to these, or truly differential effects in subpopulations of patients.Acknowledgements:Partly funded by Nordforsk and ForeumDisclosure of Interests:Bénédicte Delcoigne: None declared, Lotta Ljung: None declared, Sella Aa. Provan Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Boehringer- Ingelheim, Bente Glintborg Grant/research support from: Pfizer, BMS, AbbVie, Kathrine Lederballe Gron Grant/research support from: BMS, Merete L. Hetland Consultant of: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Niels Steen Krogh: None declared, Nina Trokovic: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, Grant/research support from: Abbvie, Celgene, Pfizer, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Brigitte Michelsen Consultant of: Novartis (paid to employer), Grant/research support from: Novartis (paid to employer), Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system.

Background:Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bio-naïve axial spondyloarthritis (axSpA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in axSpA patients initiating a first TNFi.Methods:Prospectively collected data on bio-naïve axSpA patients starting TNFi in routine care from 15 European countries were pooled. According to year of TNFi initiation, three groups were defined a priori based on bDMARD availability: Group A (1999–2008), Group B (2009–2014) and Group C (2015–2018). Retention rates (Kaplan-Meier), crude and LUNDEX adjusted1 remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) Results:In total, 27189 axSpA patients were included (5945, 11255 and 9989 in groups A, B and C).At baseline, patients in group A were older, had longer disease duration and a larger proportion of male and HLA-B27 positive patients compared to B and C, whereas disease activity was similar across groups.Retention rates at 6, 12 and 24 months were highest in group A (88%/81%/71%) but differed little between B (84%/74%/64%) and C (85%/76%/67%).In all groups, median ASDAS and BASDAI had decreased markedly at 6 months (Table 1). The ASDAS values at 12 and 24 months and BASDAI at 24 months were higher in group A compared with groups B and C. Similarly, crude remission and response rates were lowest in group A. After adjustments for drug retention (LUNDEX), remission and response rates showed less pronounced between-group differences regarding ASDAS measures and no relevant differences regarding BASDAI measures.Conclusion:Nowadays, axSpA patients initiating TNFi are younger with shorter disease duration and more frequently female and HLA-B27 negative than previously, while baseline disease activity is unchanged. Drug retention rates have decreased, whereas crude remission and response rates have increased. This may indicate expanded indication but also a stable disease activity threshold for TNFi initiation over time, an increased focus on targeting disease remission and more available treatment options.References:[1]Arthritis Rheum 2006; 54: 600-6.Table 1.Secular trends in baseline characteristics, treatment retention, remission and response rates in European axSpA patients initiating a 1st TNFiBaseline characteristicsGroup A(1999–2008)Group B(2009–2014)Group C(2015–2018)Age, years, median (IQR)57 (49–66)51 (42–60)46 (37–56)Male, %666057HLA-B27, %877772Years since diagnosis, median (IQR)5 (1–12)2 (0–8)2 (0–7)Smokers, %232425ASDAS, median (IQR)3.5 (2.8–4.1)3.4 (2.8–4.1)3.5 (2.8–4.1)BASDAI, median, (IQR)57 (42–71)59 (43–72)57 (41–71)TNFi drug, % (Adalimumab /Etanercept / Infliximab /Certolizumab / Golimumab)22 / 35 / 43 / 0 / 037 / 21 / 20 / 4 / 1827 / 28 / 24 / 8 / 13Follow up6 months12 months24 monthsGr AGr BGr CGr AGr BGr CGr AGr BGr CRetention rates, %, (95% CI)88 (88–89)84 (83–85)85 (84–86)81 (80–82)74 (74–75)76 (75–76)71 (70–72)64 (63–65)67 (66–68)ASDAS, median, (IQR)1.8 (1.2–2.8)1.9 (1.2–2.8)1.8 (1.2–2.6)1.9 (1.3–2.6)1.7 (1.2–2.5)1.6 (1.1–2.4)1.9 (1.4–2.6)1.7 (1.1–2.4)1.5 (1.1–2.2)ASDAS inactive disease, %, c/L28 / 2528 / 2430 / 2624 / 1932 / 2434 / 2623 / 1634 / 2039 / 23ASDAS CII, %, c/L57 / 5159 / 5063 / 5461 / 5063 / 4767 / 5159 / 4168 / 4074 / 45ASDAS MI, %, c/L31 / 2732 / 2737 / 3232 / 2637 / 2741 / 3130 / 2042 / 2546 / 28BASDAI, median, (IQR)23 (10–40)26 (11–48)24 (10–44)21 (10–38)23 (10–42)20 (8–39)22 (9–40)20 (8–39)16 (6–35)BASDAI remission, %, c/L44 / 4040 / 3443 / 3645 / 3645 / 3450 / 3844 / 3048 / 2956 / 34BASDAI 50 response, %, c/L53 / 4750 / 4253 / 4557 / 4656 / 4258 / 4457 / 3960 / 3563 / 38Gr, Group; c/L, crude/LUNDEX adjusted.Acknowledgements:Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network.Disclosure of Interests:Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Sara Nysom Christiansen Speakers bureau: BMS and GE, Grant/research support from: Novartis, Simon Horskjær Rasmussen: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Ulf Lindström: None declared, Jakub Zavada: None declared, Florenzo Iannone: None declared, Fatos Onen: None declared, Michael J. Nissen Speakers bureau: Novartis, Eli Lilly, Celgene, and Pfizer, Consultant of: Novartis, Eli Lilly, Celgene, and Pfizer, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Maria Jose Santos Speakers bureau: AbbVie, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GlaxoSmithKline, Dan Nordström Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, Roche, UCB, Manuel Pombo-Suarez: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Irene van der Horst-Bruinsma Speakers bureau: Abbvie, BMS, MSD, Novartis, Pfizer, Lilly, UCB, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Johan Askling: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen, AbbVie, Karel Pavelka Speakers bureau: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Consultant of: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Elisa Gremese: None declared, Nurullah Akkoc: None declared, Adrian Ciurea Speakers bureau: Abbvie, Eli-Lilly, MSD, Novartis, Pfizer, Eirik kristianslund: None declared, Anabela Barcelos: None declared, Gareth T. Jones Grant/research support from: Pfizer, AbbVie, UCB, Celgene, Amgen, GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Carlos Sánchez-Piedra: None declared, Ruxandra Ionescu Speakers bureau: Abbvie, Amgen, Boehringer-Ingelheim Eli-Lilly,Novartis, Pfizer, Sandoz, UCB, Ziga Rotar Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Marleen G.H. van de Sande: None declared, Arni Jon Geirsson: None declared, Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Merete L. Hetland Speakers bureau: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis.

Background:Interstitial lung disease (ILD) is an established extra-articular manifestation of rheumatoid arthritis (RA). Few studies have investigated the prevalence of ILD in patients with psoriatic arthritis (PsA). Methotrexate (MTX) is frequently used in the treatment of both RA and PsA and has been suggested to be a risk factor for the development of ILD. It is of interest to understand the interaction between disease and treatment in the development of ILD.Objectives:To compare the incidence of ILD between patient with PsA and RA treated with biologic disease modifying antirheumatic drugs (bDMARDS), with or without MTX as a co-medication.Methods:Cohorts of patients with RA and PsA starting bDMARD were identified in Nordic registers (Danish nationwide clinical register for patients with RA (DANBIO), Register on antirheumatic and biological therapy in Finland (ROB-FIN), Icelandic nationwide database of biologic therapy (ICEBIO), Norwegian Antirheumatic Drug Register (NOR-DMARD), and the Swedish Rheumatology Quality Register (SRQ)). Linkages to the National Patient Registers and to the Cause of Death Registers were performed in each country to identify cases of ILD. Each individual patient could contribute several treatment courses. ILD was identified as hospital or death certificate ICD10 codes of ILD (J84.1, J84.8, J84.9, J70.2, J70.3, J70.4, J99.0, J99.1, J99.8) given during the follow-up period which was defined as the treatment course duration, plus a 30-day wash-out period added to the end of treatment course period. MTX co-medication was specified as use of MTX at the start of bDMARD. Incidence rates (IR) for any ILD were calculated per 1000 person years at risk (PYR) for each country. The five cohorts were pooled and incidence rate ratios (IRR) for PsA vs. RA were calculated. Hazard ratios (HR) for any ILD in PsA vs. RA were estimated in Cox regression models adjusted for age, gender and repeated observations, and stratified for the use of MTX co-medication.Results:Overall 47 987 individual patients representing 89 239 bDMARD treatment courses and contributing 201 279 PYR were included in the study (Table 1). Methotrexate was reported as comedication in 29 916 (33.5 %) of the treatment courses (PsA vs. RA, 30.4 % vs 34.5 %). 970 cases of ILD were identified during the follow-up period. The risk of ILD was consistently lower in patients with PsA compared to patients with RA in all countries. In models stratified for co-medication the HR for ILD in PsA vs. RA was 0.34 (0.21-0.57) in patients treated with MTX and 0.26 (0.18-0.36) in patients not treated with MTX.Table 1.Interstitial lung disease in PsA vs. RA in five Nordic biologic registersDENMARKFINLANDICELANDNORWAYSWEDENRAPsARAPsARAPsARAPsARAPsANumber of individuals78293386494610916754701590999205966393Number of treatment courses17 07266408634184512808592379142738 27910 824Age baseline (SD)57.3 (13.1)49.0 (12.6)53.8 (13.4)48.8 (11.4)53.9 (14.2)50.1 (13.3)53.8 (13.7)48.7 (12.0)57.1 (13.7)50.6 (12.8)Female n (%)12 963 (76)3929 (59)6571 (76)933 (51)969 (76)551 (65)1815 (77)818 (57)29 635 (77)6162 (57)Number of PYR4023513986217984910451727994556265312033427412ILD-events within PYR2182213287232668028IR pr 1000 PYR5.41.66.11.61.50.77.02.35.71.0IRR PsA vs RA crude0.29 (0.18-0.45)0.27 (0.11-0.55)0.46 (0.05-2.42)0.32(0.11-0.78)0.18 (0.12-0.26)HR PsA vs RA0.31 (0.17-0.56)0.46 (0.22-0.96)0.62 (0.12-3.14)0.19 (0.06-0.54)0.25 (0.17-0.37)PYR: Patient years at risk, IR: Incidence rates, IRR: Incidence rate ratios, HR: Hazard RatiosConclusion:In these preliminary analyses, the incidence of ILD is lower in bDMARD treated PsA vs. RA patients, irrespective of co-medication with MTX. This indicates that the clinician should consider the rheumatological diagnosis when assessing the risk for future ILD in patients treated with bDMARDs and MTX.Acknowledgements:Partly funded by NordForsk and FOREUMDisclosure of Interests:Sella Aarrestad Provan Consultant of: Novartis, Grant/research support from: Boehringer-Ingelheim, Brigitte Michelsen: None declared, Lotta Ljung: None declared, Thorarinn Jonmundsson: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Daniela Di Giuseppe: None declared, Merete Lund Hetland Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Consultant of: Eli Lilly, Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Guðrún Björk Reynisdóttir: None declared, Bente Glintborg: None declared, Eirik kristianslund: None declared, Heikki Relas: None declared, Kalle Aaltonen: None declared, Dan Nordström Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi., Consultant of: AbbVie, Amgren, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi., Johan Askling Grant/research support from: Abbvie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, and Sanofi

Background:In clinical practice, some patients with axial spondyloarthritis (axSpA) fail several consecutive biological treatments (bDMARDs). How this group of ”refractory” patients should best be defined, how common they are, and what their characteristics are, is poorly understood.Objectives:To explore the point prevalence of bDMARD refractory disease in axSpA over time, according to different definitions, and to describe the characteristics of refractory vs. not-refractory patients upon start of their first bDMARD.Methods:Observational prospective cohort study. Patients with axSpA (ankylosing spondylitis/non-radiographic axial SpA) starting a first bDMARD 2009-2018 were identified in biologic registries in Denmark, Sweden, Finland, Norway and Iceland. Clinical characteristics and treatments were retrieved, and data were pooled for analysis.Refractory disease was defined based on the number of different bDMARD treatments started in individual patients: mild (≥3 bDMARDs), moderate (≥4), and strict (5 or more). Restart of same bDMARD with another bDMARD in between counted as separate courses whereas switch from originator to corresponding biosimilar was ignored.Proportions of patients fulfilling each definition of refractory disease at 2 and 5 years after the start of 1st bDMARD were calculated.Point-prevalence per calendar-year was calculated as the number of patients with refractory disease at the end of each year, divided by the total number of patients ever having starting a first bDMARD before that time-point, and who were still alive and resident in the country.Results:The point prevalence of refractory axSpA increased with calendar-time (Figure). Among 12,037 included axSpA patients (64% male), the point-prevalence of bDMARD refractory disease in 2018 was 16%/7%/3% according to mild/moderate/strict definitions (Table).Table 1.Biologic refractory axSpA according to three definitionsA.Baseline characteristics upon start 1st bDMARDRefractory definitionOverall cohortMILDMODERATESTRICTN120371969832351Age, years42 (13)41 (12)41 (12)41 (12)Male, %64%57%54%56%Disease duration, years7 (10)6 (9)6 (8)5 (8)BASDAI, 0-10053 (28)60 (29)63 (27)66 (35)ASDAS3.3 (1.1)3.5 (1.2)3.6 (1.0)3.7 (1.1)CRP, mg/L16 (23)18 (26)21 (28)23 (32)Patient global, VAS, 0-10059 (25)65 (22)66 (22)67 (23)Patient Pain, VAS, 0-10057 (24)62 (22)63 (22)63 (22)Fatigue, VAS, 0-10059 (27)66 (26)66 (26)68 (25)B.Proportions of patients having refractory disease 2 and 5 years after start of their first bDMARD2 years, %5%1%0%5 years, %13%4%1%Numbers are means (SD) unless otherwise statedUpon start of their 1st bDMARD, patients later fulfilling the definitions for refractory axSpA were more frequently women, had shorter disease duration, higher C-reactive protein and higher patient reported outcomes.Overall, 5%/1%/0% had mild/moderate/strict refractory disease 2 years after start of first bDMARD, after 5 years it was 13%/4%/1% (Table).Conclusion:In this large Nordic observational cohort of axSpA patients treated in routine care, we could demonstrate that a substantial proportion of all patients had used multiple bDMARDs. In 2018, one in six patients had received ≥3 bDMARDs, indicating a bDMARD refractory disease. Multiple switching was more frequent during later years, probably due to more bDMARDs becoming available. The characteristics of refractory axSpA, including sex and disease activity, will have to be further explored, as will the impact of refractory disease on long-term outcomes.Acknowledgements:the DANBIO, SRQ, ICEBIO, ROB-FIN and NOR-DMARD registries.Partly sponsored by Nordforsk and Foreum.Disclosure of Interests:Daniela Di Giuseppe: None declared, Ulf Lindström: None declared, Kalle Aaltonen: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, MSD, Roche, Sella Aarrestad Provan: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, 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 spondyloarthritis based on secondary use of quality data and is partly funded by Novartis., Johan Askling: None declared, Tanja Schjødt Jørgensen: None declared, Lene Dreyer Speakers bureau: Eli-Lilly and Galderma, Grant/research support from: BMS, Dan Nordström: None declared, Brigitte Michelsen: None declared, Arni Jon Geirsson: None declared, Lennart T.H. Jacobsson: None declared, Bente Glintborg Grant/research support from: Abbvie, BMS, Pfizer, Lundbeck foundation

Introduction Sleep disturbances, fatigue, and anxiety/depression in psoriatic arthritis (PsA) may be influenced by skin and musculoskeletal manifestations. All of these in turn affect the psychosocial impact of disease. The objective was to explore the occurrence of sleep disturbances, fatigue, and anxiety/depression in psoriatic arthritis (PsA) patients, and their correlates. Methods A broad data collection was performed in 137 Norwegian PsA outpatient clinic patients including demographics, disease activity measures for both skin and musculoskeletal involvement, and patient-reported outcome measures. Sleep disturbances and fatigue were defined present if the numeric rating scale (0–10) score was ≥ 5. Anxiety/depression was assessed using a questionnaire (1–3; 1 defined as no anxiety/depression). Descriptive statistics was applied, and associations were explored using univariate and adjusted linear regression analysis. Results The mean age was 52.3 years, PsA disease duration 8.8 years; 49.6% were men and 54.8% were currently employed/working. The prevalence of sleep disturbances was 38.0%, fatigue 44.5%, and anxiety/depression 38.0%. In adjusted analysis, pain, fatigue, and higher mHAQ were associated with sleep disturbances. Sleep disturbances, pain, and anxiety/depression were associated with fatigue, whereas only fatigue was associated with anxiety/depression. Conclusions The prevalence of sleep disturbances, fatigue, and anxiety/depression was frequently reported by PsA patients. No measures reflecting skin involvement or objective measures of musculoskeletal involvement were independently associated with sleep disturbances, fatigue, or anxiety/depression. Our data suggest that patients’ perceptions of musculoskeletal involvement (pain or mHAQ) play an important role causing sleep disturbances and fatigue, whereas fatigue in PsA patients is strongly associated with anxiety/depression.

Objectives To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA. Methods All patients with PsA starting secukinumab or a TNFi in 2015–2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+). Results We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar. Conclusion No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective.

BackgroundIn psoriatic arthritis (PsA), both psoriasis and musculoskeletal manifestations may impair Health-Related Quality of Life (HRQoL). Our objective was to explore the impact of the various disease manifestations and disease consequences, including psychosocial factors, on HRQoL in PsA patients treated in the biologic treatment era.MethodsData collection in the 131 outpatient clinic PsA patients assessed included demographics, disease activity measures for both skin and musculoskeletal involvement and patient-reported outcome (PRO) measures, treatment and psychosocial burden. The skin dimension of quality of life was assessed by the Dermatology Life Quality Index (DLQI) and the overall HRQoL by the 15-Dimensional (15D) Questionnaire.ResultsThe mean age was 51.9 years, PsA disease duration 8.6 years, 50.4% were men, 56.9% were employed/working and 47.7% had ≥1 comorbidities. Prevalence of monotherapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was 36.6% and with biologic DMARDs 12.2% and combination of both 22.9%. Mean DLQI was 3.3 and 15D 0.84. In adjusted analysis, not employed/working, higher scores for fatigue, sleep disturbances, anxiety and depression, Modified Health Assessment Questionnaire and presence of comorbidities were independently associated with impaired HRQoL (lower 15D scores), whereas Psoriasis Area Severity Index (PASI) and DLQI were not. Younger age and higher Psoriatic Arthritis Disease Activity Score and PASI scores were independently associated with impaired skin quality of life (higher DLQI score).ConclusionOur study highlights the negative impact the psychosocial burden, impaired physical function and comorbidities has on reduced HRQoL in PsA outpatients. Thus, to further improve HRQoL in PsA patients, not only physical concerns but also psychological concerns need to be addressed.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved., Objectives: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. Methods: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. Results: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P

Publisher's version (útgefin grein), OBJECTIVES: To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries. METHODS: Real-life data from 13 European registries participating in the European Spondyloarthritis Research Collaboration Network were pooled. Kaplan-Meier with log-rank test, Cox regression, χ² and logistic regression analyses were performed to assess 6-month and 12-month secukinumab retention, inactive disease/low-disease-activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), The EuroSpA collaboration was financially supported by Novartis. Novartishad no influence on the data collection, statistical analyses, manuscript preparationor decision to submit. The national registries have received financial support froma range of pharmaceutical companies, including Novartis. These funds are given asunrestricted grants

Background:Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bionaïve psoriatic arthritis (PsA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in PsA patients initiating a first TNFi.Methods:Prospectively collected data on bionaïve PsA patients starting TNFi in routine care from 15 European countries were pooled. According to year of TNFi initiation, three groups were defined a priori based on bDMARD availability: Group A (1999–2008), Group B (2009–2014) and Group C (2015–2018).Retention rates (Kaplan-Meier), crude and LUNDEX adjusted1 remission (Disease Activity Score (DAS28) Results:A total of 17453 PsA patients were included (4069, 7551 and 5833 in groups A, B and C).Patients in group A were older and had longer disease duration compared to B and C. Retention rates at 6, 12 and 24 months were highest in group A (88%/77%/64%) but differed little between B (83%/69%/55%) and C (84%/70%/56%).Baseline disease activity was higher in group A than in B and C (DAS28: 4.6/4.3/4.0, DAPSA28: 29.9/25.7/24.0, CDAI: 21.8/20.0/18.6), and this persisted at 6 and 12 months. Crude and LUNDEX adjusted remission rates at 6 and 12 months tended to be lowest in group A, although crude/LUNDEX adjusted ACR50 response rates at all time points were highest in group A. At 24 months, disease activity and remission rates were similar in the three groups (Table).Table 1.Secular trends in baseline characteristics, treatment retention, remission and response rates in European PsA patients initiating a 1st TNFiBaseline characteristicsGroup A(1999–2008)Group B(2009–2014)Group C(2015–2018)Age, median (IQR)62 (54–72)58 (49–67)54 (45–62)Male, %514847Years since diagnosis, median (IQR)5 (2–10)3 (1–9)3 (1–8)Smokers, %161717DAS28, median (IQR)4.6 (3.7–5.3)4.3 (3.4–5.1)4.0 (3.2–4.8)DAPSA28, median (IQR)29.9 (19.3–41.8)25.7 (17.2–38.1)24.0 (16.1–35.5)CDAI, median (IQR)21.8 (14.0–31.1)20.0 (13.0–29.0)18.6 (12.7–26.1)TNFi drug, % (Adalimumab / Etanercept / Infliximab / Certolizumab / Golimumab)27 / 43 / 30 / 0 / 036 / 31 / 14 / 5 / 1421 / 40 / 21 / 8 / 10Follow up6 months12 months24 monthsGr AGr BGr CGr AGr BGr CGr AGr BGr CRetention rates, % (95% CI)88 (87–89)83 (82–84)84 (83–85)79 (78–80)72 (71–73)72 (71–73)68 (67–69)60 (59–61)60 (59–62)DAS28, median (IQR)2.7 (1.9–3.6)2.4 (1.7–3.4)2.3 (1.7–3.2)2.5 (1.8–3.4)2.2 (1.6–3.1)2.1 (1.6–2.9)2.1 (1.6–3.1)2.0 (1.6–2.9)1.9 (1.5–2.6)DAPSA28, median (IQR)10.6 (4.8–20.0)9.5 (3.9–18.3)8.7 (3.6–15.9)9.1 (4.1–17.8)7.7 (3.1–15.4)7.6 (2.9–14.4)6.7 (2.7–13.7)6.6 (2.7–13.5)5.9 (2.4–11.8)CDAI, median (IQR)7.8 (3.0–15.2)8.0 (3.0–15.0)6.4 (2.6–12.2)6.4 (2.5–13.0)6.2 (2.5–12.1)5.8 (2.2–11.4)5.0 (2.0–11.0)5.5 (2.0–11.2)5.0 (2.0–9.0)DAS28 remission, %, c/L47 / 4255 / 4661 / 5153 / 4362 / 4566 / 4864 / 4268 / 3775 / 41DAPSA28 remission, %, c/L22 / 1926 / 2228 / 2325 / 2031 / 2232 / 2336 / 2334 / 1938 / 21CDAI remission, %, c/L23 / 2123 / 1926 / 2227 / 2127 / 2029 / 2134 / 2231 / 1735 / 19ACR50 response, %, c/L26 / 2322 / 1824 / 2027 / 2223 / 1721 / 1523 / 1518 / 1014 / 8Gr, Group; c/L, crude/LUNDEX.Conclusion:Over the past 20 years, patient age, disease duration and disease activity level at the start of the first TNFi in PsA patients have decreased. Furthermore, TNFi retention rates have decreased while remission rates have increased, especially remission rates within the first year of treatment. These findings may reflect a greater awareness of early diagnosis in PsA patients, a lowered threshold for initiating TNFi and the possibility for earlier switching in patients with inadequate treatment response.References:[1]Arthritis Rheum 2006; 54: 600-6.Acknowledgements:Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network.Disclosure of Interests:Sara Nysom Christiansen Speakers bureau: BMS and GE, Grant/research support from: Novartis, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Simon Horskjær Rasmussen: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis, Florenzo Iannone Speakers bureau: Abbvie, MSD, Novartis, Pfizer and BMS, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Michael J. Nissen Speakers bureau: Novartis, Eli Lilly, Celgene, and Pfizer, Consultant of: Novartis, Eli Lilly, Celgene, and Pfizer, Jakub Zavada: None declared, Maria Jose Santos Speakers bureau: AbbVie, Novartis, Pfizer, Manuel Pombo-Suarez: None declared, Kari Eklund: None declared, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, İsmail Sari: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Daniela Di Giuseppe: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen, AbbVie, Marco Sebastiani: None declared, Karen Minde Fagerli: None declared, Burkhard Moeller: None declared, Karel Pavelka Speakers bureau: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Consultant of: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Anabela Barcelos: None declared, Carlos Sánchez-Piedra: None declared, Heikki Relas: None declared, Ziga Rotar Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Thorvardur Love: None declared, Servet Akar: None declared, Ruxandra Ionescu Speakers bureau: Abbvie, Amgen, Boehringer-Ingelheim Eli-Lilly,Novartis, Pfizer, Sandoz, UCB, Gary Macfarlane Grant/research support from: GlaxoSmithKline, Marleen G.H. van de Sande: None declared, Merete L. Hetland Speakers bureau: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis., Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth

Background:Women with rheumatoid arthritis (RA) are at increased risks of adverse pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA). However, the link between RA disease activity, type and timing of anti-rheumatic treatment, and the risk of these outcomes remains unclear.Objectives:To explore the associations between maternal RA and PTB/SGA in relation to disease activity and use of anti-rheumatic treatment before and during pregnancy.Methods:By linking national medical birth registers to prospective clinical rheumatology registers (CRRs) in Sweden (SRQ) and Denmark (DANBIO), we identified 1739 RA-pregnancies and 17390 control-pregnancies (matched 1:10 on maternal age, birth year, and parity) with delivery 2006-2018. From CRRs and prescribed drug registers, we collected information on RA disease activity (DAS28, CRP and HAQ-score) and anti-rheumatic drugs (biologics, conventional synthetic (cs)DMARDs and oral steroids) nine months before and during pregnancy. Using logistic regression, we estimated adjusted odds ratios (ORs) with 95% confidence intervals (CI) for PTB and SGA in RA-pregnancies vs. control-pregnancies overall, and stratified by disease activity and type of anti-rheumatic treatment before and during pregnancy. Apart from the matching variables we adjusted for body mass index, smoking, educational level and country.Results:Overall, RA-pregnancies were associated with increased ORs of PTB (1.92, 95% CI 1.56-2.35) and SGA (1.93, 95% CI 1.45-2.57). High maternal disease activity during pregnancy strengthened the associations with both PTB and SGA, whereas the ORs approached 1 for low disease activity (control-pregnancies constituting the reference), Table 1. Among RA-pregnancies with available information on DAS28-CRP (n=686, 39%), OR was 2.69 (95% CI 1.37-5.26) for PTB, and 3.39 (95% CI 1.43-8.06) for SGA, comparing DAS28-CRP >=3.2 vs.Table 1.Adjusted odds ratios (ORs)1 for PTB and SGA in RA-pregnancies in relation to disease activity and functional status during pregnancy vs. control pregnanciesPreterm birthSmall for gestational age1Pregnancies, nEvents,n (%)Adjusted OR(95% CI)Pregnancies, nEvents,n (%)Adjusted OR(95% CI)Control-pregnancies217312794 (5)1 (REF)17184418 (2)1(REF)All RA pregnancies21734144 (8)1.92 (1.56-2.35)172275 (4)1.93 (1.45-2.57)DAS28-CRP3,445926 (6)1.05 (0.64-1.72)45613 (3)0.96 (0.49-1.91)3.2-5.118217 (9)2.40 (1.40-4.11)18113 (7)3.13 (1.64-5.97)>5.1435 (12)2.77 (0.86-8.87)434 (9)4.59 (1.59-13.2)No information105096 (9)2.18 (1.71-2.78)104245 (4)2.06 (1.46-2.90)HAQ-score333819 (6)1.31 (0.79-2.16)3358 (2)0.93 (0.41-2.12)0.5-0.916615 (9)2.37 (1.34-4.19)1655 (3)1.50 (0.60-3.74)≥119619 (10)1.85 (1.06-3.24)19518 (9)3.70 (2.05-6.67)No information103491 (9)2.06 (1.60-2.64)102744 (4)1.98 (1.39-2.82)CRP, mg/L345521 (5)0.91 (0.55-1.51)45214 (3)1.09 (0.57-2.07)10-2919122 (11)2.58 (1.52-4.38)19012 (6)2.68 (1.38-5.22)≥30579 (16)4.59 (2.28-9.22)575 (9)4.12 (1.68-10.1)No information103192 (9)2.10 (1.64-2.70)102344 (4)2.05 (1.44-2.90)1Missingness on small for gestational age in 12 RA-pregnancies and 128 control-pregnancies 2Only among live births, i.e. stillbirths excluded. 3Maximum value any time during pregnancy 4Defined as DAS28-CRP without patient’s global health VASConclusion:During pregnancy, disease activity rather than treatment, appears to be the most important risk factor for PTB and SGA in RA. The findings highlight the importance of monitoring RA during pregnancy, especially in women receiving extensive anti-rheumatic treatment or with residual disease activity.Acknowledgements:The Nordic clinical rheumatology registers for allowing us to use their clinical data. We also would like to acknowledge the NordForsk and FOREUM, especially the patient representatives of the NordForsk collaboration.Disclosure of Interests:Karin Hellgren Consultant of: UCB, Anne Emilie Secher: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen and BMS, Ane Lilleoere Rom: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Fredrik Granath: None declared, Merete Lund Hetland Speakers bureau: Biogen, Celltrion, Janssen Biologics B.V, MSD, Pfizer, Samsung Biopis, Consultant of: Biogen, Celltrion, Janssen Biologics B.V, MSD, Pfizer, Samsung Biopis, Grant/research support from: AbbVie, Biogen, BMS, Eli Lilly Danmark A/S, Lundbeck Fonden, Pfizer, Roche, Sandoz, Novartis

ObjectiveTo investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up.MethodsWe included 1326 patients with RA and 728 patients with PsA from the prospective observational NOR-DMARD study starting first-time tumour necrosis factor inhibitors or methotrexate. The predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models.ResultsBaseline depression/anxiety according to EuroQoL-5D-3L, Short Form-36 (SF-36) Mental Health subscale ≤56 and SF-36 Mental Component Summary ≤38 negatively predicted 28-joint Disease Activity Score ConclusionDepression and anxiety may reduce likelihood of joint remission based on composite scores in RA and PsA and should be taken into account in individual patients when making a shared decision on a treatment target.

Objective.To explore the burden of skin, joint, and entheses manifestations in a representative psoriatic arthritis (PsA) outpatient cohort in the biologic treatment era.Methods.This was a cross-sectional study of 141 PsA outpatients fulfilling the ClASsification for Psoriatic ARthritis (CASPAR) criteria and examined between January 2013 and May 2014. Selected disease activity measures were explored including Disease Activity index for PSoriatic Arthritis (DAPSA), Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Score for 28 joints (DAS28), Simplified Disease Activity Index (SDAI), and Psoriasis Area Severity Index (PASI). Dermatology Life Quality Index (DLQI), minimal disease activity (MDA), and remission criteria were assessed.Results.Median (range) DAPSA was 14.5 (0.1–76.4), CPDAI 5 (1–11), PASDAS 3.1 (2.1–4.2), DAS28-erythrocyte sedimentation rate (ESR) 3.2 (0.6–6.4), SDAI 8.6 (0.1–39.5), PASI 1.2 (0.0–19.7), and DLQI 2.0 (0–17). The MDA criteria were fulfilled by 22.9% of the patients. DAPSA ≤ 4, CPDAI ≤ 2, PASDAS < 2.4, DAS28-ESR < 2.4, SDAI < 3.3, and Boolean’s remission criteria were fulfilled by 12.1, 9.3, 7.8, 26.2, 21.3, and 5.7% of patients, respectively. The number of satisfied patients was similar regardless of whether the group was treated with tumor necrosis factor inhibitors.Conclusion.Our real-life data indicate that there is still a need for improvement in today’s treatment of PsA. Musculoskeletal inflammatory involvement was more prominent than psoriatic skin involvement. Only a few patients fulfilled the DAPSA, PASDAS, and CPDAI remission criteria, and about a quarter fulfilled the MDA criteria. Considerably fewer patients fulfilled PsA-specific remission criteria versus non-PsA specific remission criteria. Still, patient satisfaction was good and PASI and DLQI were low.

Background:Axial spondylarthritis (axSpA) patients treated with a tumour necrosis factor inhibitor (TNFi) may receive a concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), although the value of combination therapy remains unclear.Objectives:Describe the proportion and phenotype of patients with axSpA initiating their first TNFi as monotherapy compared to TNFi+csDMARD combination therapy, and to compare the 1-year TNFi retention between the two groups.Methods:Data from 13 European registries was collected. Two exposure treatment groups were defined: TNFi monotherapy at baseline (=TNFi start date) and TNFi+csDMARD combination therapy. TNFi retention rates were assessed with Kaplan-Meier curves for each country and combined. Hazard ratios (HR, 95% CI) for discontinuing the TNFi were obtained with Cox models: (i) crude; adjusted for (ii) country, and (iii) country, sex, age, calendar year, disease duration and BASDAI. Participating countries were dichotomized into two strata, depending on their 1-year retention rate being above (stratum A) or below (stratum B) the average retention rate across all countries.Results:22,196 axSpA patients were included with 34% on TNFi+csDMARD combination therapy. Baseline characteristics are presented in table 1. Overall, the crude TNFi retention rate was marginally longer in the combination therapy group (80% (79-81%)) compared to the monotherapy group (78% (77-79%)) and was primarily driven by differences in stratum B (fig. 1). TNFi retention rates varied significantly across countries (range:-11.0% to +11.3%), with a clear distinction between the 2 strata. The HRs for discontinuation over 1-year (reference=TNFi monotherapy) in the 3 models were: (i) 0.88 (0.82-0.93), (ii) 0.87 (0.82-0.92), (iii) 0.88 (0.82-0.93).Table 1Baseline characteristicsAll patients(n=22196)Country stratum ACountry stratum BTNFi mono(n=4940)csDMARD + TNFi(n=2547)TNFi mono(n=9693)csDMARD + TNFi(n=5016)Age (years), mean (SD)42.6 (12.5)43.4 (12.0)42.8 (12.2)41.6 (12.7)43.7 (12.7)Females, %41.137.738.242.044.2Disease duration (yrs), mean (SD)5.7 (8.0)6.2 (7.7)6.7 (7.4)4.9 (8.2)6.1 (8.2)Enthesitis, %50.316.733.957.859.7SJC-28, median (IQR)0 (0-1)0 (0-0)0 (0-2)0 (0-0)0 (0-2)VAS pain (0-100), mean (SD)60.9 (24.5)63.3 (26.5)67.8 (23.3)60.2 (23.4)57.2 (24.3)CRP (mg/L), median (IQR)8 (3-20)7.8 (2-20)18 (6.7-32.6)6.0 (2.7-15)8.0 (3-22)BASDAI (0-10), mean (SD)5.7 (2.1)5.7 (2.2)6.2 (2.1)5.6 (2.0)5.4 (2.2)BASFI (0-10), mean (SD)4.4 (2.5)4.4 (2.6)4.9 (2.5)4.3 (2.4)4.2 (2.9)ASDAS, mean (SD)3.5 (1.1)3.7 (1.0)4.0 (1.0)3.3 (1.0)3.3 (1.1)On Infliximab, %25.721222436Baseline csDMARD use, %-Methotrexate045063-Sulfasalazine068033-Leflunomide0801Conclusion:Considerable differences were observed across countries in the use of combination therapy and TNFi retention in axSpA patients. The overall 1-year TNFi retention was higher with csDMARD co-therapy compared to TNFi monotherapy. TNFi monotherapy had a 12-13% higher risk of treatment discontinuation.Acknowledgments:Novartis Pharma AG and IQVIAMN and BD participated equallyDisclosure of Interests:Michael Nissen Grant/research support from: Abbvie, Consultant of: Novartis, Lilly, Abbvie, Celgene and Pfizer, Speakers bureau: Novartis, Lilly, Abbvie, Celgene and Pfizer, Bénédicte Delcoigne: None declared, Daniela Di Giuseppe: None declared, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Karen Fagerli: 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, Adrian Ciurea Consultant of: Consulting and/or speaking fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer., Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Heřman Mann: None declared, Nurullah Akkoc: None declared, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Brigitte Michelsen: None declared, Gary Macfarlane: 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, Matija Tomsic: None declared, Burkhard Moeller: None declared, Pedro Ávila-Ribeiro Grant/research support from: Novartis, Carlos Sánchez-Piedra: None declared, Heikki Relas Grant/research support from: Abbvie., Consultant of: Abbvie, Celgene, and Pfizer., Speakers bureau: Abbvie, Celgene, and Pfizer., Arni Jon Geirsson: None declared, Lucie Nekvindova: None declared, Gozde Yildirim Cetin Speakers bureau: AbbVie, Novartis, Pfizer, Roche, UCB, MSD, Ruxandra Ionescu Consultant of: Consulting fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Speakers bureau: Consulting and speaker fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Niels Steen Krogh: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Ulf Lindström: None declared