SAT0424 Axial disease in psoriatic arthritis: burden of underdiagnosed disease and risk factors in real life

At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)- Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a pilot investigator-initiated study protocol to test electronic case report forms (eCRFs) and proposed Standardized Operating Procedures (SOPs) to evaluate biomarkers of psoriatic arthritis (PsA) associated with axial disease. The progress on 3 studies was also presented: BioDAM PsA (Biomarkers as Predictors of structural DAMage in PsA; to validate soluble biomarkers as predictors of structural damage in PsA), PreventPsA (examining the development of PsA and risk factors among patients with psoriasis and no arthritis), and PredictORPsA (Predicting Treatment respOnse in patients with eaRly PsA; in collaboration with Pfizer using samples from the Oral Psoriatic Arthritis TriaL [OPAL], to identify biomarkers of treatment response). GRAPPA-CRN funding partnerships and applications are also underway with both the Innovative Medicines Initiative (IMI) in Europe and Accelerating Medicines Partnerships (AMP) 2.0 in the USA, and the progress of these applications and associated objectives were presented.

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POS1015 ANTI-TNF DRUGS AND CARDIOVASCULAR EVENTS IN PATIENTS WITH SPONDYLOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4133 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 775.2-776

Author(s):

C. W. S. Chan ◽

P. H. LI ◽

C. S. Lau ◽

H. Y. Chung

Keyword(s):

Risk Factors ◽

Psoriatic Arthritis ◽

Cardiovascular Events ◽

Clinical Information ◽

Incidence Rates ◽

Major Adverse Cardiovascular Events ◽

Cross Sectional ◽

Cerebrovascular Events ◽

Cardiovascular Morbidity And Mortality

Background:Cardiovascular (CVS) diseases are the leading cause of death worldwide and patients with rheumatic diseases have an increased CVS risk including stroke and myocardial infarction (MI) (1-3). CVS risk factors and CVS events are common in SpA (4). Delineating the CVS risk and the association with medications in patients with SpA would be useful.Objectives:The objective of this study was to delineate the CVS risk and the association with medications in patients with SpA.Methods:Patients with SpA and patients with non-specific back pain (NSBP) were identified in rheumatology and orthopedics clinics respectively. Clinical information and CVS events were retrieved. Incidence rates were calculated. Association analysis was performed to determine the CVS risk of SpA and other modifiable risk factors.Results:A total of 5046 patients (SpA 2616 and NSBP 2430) were included from eight centers. Over 56 484 person-years of follow-up, 160 strokes, 84 MI and 262 major adverse cardiovascular events (MACE) were identified. Hypercholesterolemia was more prevalent in SpA (SpA 34.2%, NSBP 28.7%, P<0.01). Crude incidence rates of stroke and MI were higher in SpA patients. SpA was associated with a higher risk of MACE (HR 1.66, 95%CI 1.22-2.27, P<0.01) and cerebrovascular events (HR 1.42, 95%CI 1.01-2.00, p=0.04). The use of anti-tumor necrosis factor (TNF) drugs was associated with a reduced risk of MACE (HR 0.37, 95%CI 0.17-0.80, P=0.01) and cerebrovascular events (HR 0.21, 95%CI 0.06-0.78, P=0.02).Conclusion:SpA is an independent CVS risk factor. Anti-TNF drugs were associated with a reduced CVS risk in these patients.References:[1]Crowson CS, Liao KP, Davis JM, 3rd, Solomon DH, Matteson EL, Knutson KL, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622-8 e1.[2]Verhoeven F, Prati C, Demougeot C, Wendling D. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine. 2020;87(5):413-8.[3]Liew JW, Ramiro S, Gensler LS. Cardiovascular morbidity and mortality in ankylosing spondylitis and psoriatic arthritis. Best Pract Res Clin Rheumatol. 2018;32(3):369-89.[4]Molto A, Etcheto A, van der Heijde D, Landewe R, van den Bosch F, Bautista Molano W, et al. Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study. Ann Rheum Dis. 2016;75(6):1016-23.Disclosure of Interests:None declared.

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Cumulative Risks from Stressor Exposures and Personal Risk Factors in the Workplace: Examples from a Scoping Review

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18115850 ◽

2021 ◽

Vol 18 (11) ◽

pp. 5850

Author(s):

Mary A. Fox ◽

Richard Todd Niemeier ◽

Naomi Hudson ◽

Miriam R. Siegel ◽

Gary Scott Dotson

Keyword(s):

Risk Factors ◽

Risk Assessment ◽

Scoping Review ◽

Multiple Stressors ◽

Cumulative Risk ◽

Real Life ◽

Personal Factors ◽

Exposure Limits ◽

Personal Risk ◽

Personal Risk Factors

Protecting worker and public health involves an understanding of multiple determinants, including exposures to biological, chemical, or physical agents or stressors in combination with other determinants including type of employment, health status, and individual behaviors. This has been illustrated during the COVID-19 pandemic by increased exposure and health risks for essential workers and those with pre-existing conditions, and mask-wearing behavior. Health risk assessment practices for environmental and occupational health typically do not incorporate multiple stressors in combination with personal risk factors. While conceptual developments in cumulative risk assessment to inform a more holistic approach to these real-life conditions have progressed, gaps remain, and practical methods and applications are rare. This scoping review characterizes existing evidence of combined stressor exposures and personal factors and risk to foster methods for occupational cumulative risk assessment. The review found examples from many workplaces, such as manufacturing, offices, and health care; exposures to chemical, physical, and psychosocial stressors combined with modifiable and unmodifiable determinants of health; and outcomes including respiratory function and disease, cancers, cardio-metabolic diseases, and hearing loss, as well as increased fertility, menstrual dysfunction and worsened mental health. To protect workers, workplace exposures and modifiable and unmodifiable characteristics should be considered in risk assessment and management. Data on combination exposures can improve assessments and risk estimates and inform protective exposure limits and management strategies.

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POS0239 ROOT JOINT INVOLVEMENT IN SPONDYLOARTHRITIS: A POST-HOC ANALYSIS FROM THE INTERNATIONAL ASAS-PERSPA STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.651 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 340.1-341

Author(s):

N. Ziade ◽

J. El-Hajj ◽

J. Rassi ◽

S. Hlais ◽

C. López-Medina ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Positive Answer ◽

Categorical Variables ◽

Joint Involvement ◽

Main Diagnosis ◽

Post Hoc Analysis ◽

Wall Distance ◽

History Of ◽

Axial Disease ◽

Post Hoc

Background:In patients with spondyloarthritis (SpA), root joint diseases (RJD), i.e. hip or shoulder involvement, may be associated with a distinct disease phenotype compared to those with other affected joints. The ASAS-PerSpA study (PERipheral involvement in SPondyloArthritis) [1], offers a unique opportunity to study the phenotypes of patients with RJD in a global cohort.Objectives:Primary objective was to compare the clinical characteristics of SpA patients with and without RJD. Secondary objectives were to compare the prevalence of RJD across the different SpA subtypes and the different regions of the world, compare the severity of axial disease as well as the disease burden in SpA patients with and without RJD.Methods:This is a post-hoc analysis of the ASAS-PerSpA study, which included 4,465 patients with any subtype of SpA (axial SpA (axSpA), peripheral SpA (pSpA), psoriatic arthritis (PsA), inflammatory bowel disease associated SpA (IBD-SpA), reactive arthritis (ReA) and Juvenile SpA (Juv-SpA)) according to the rheumatologist’s diagnosis. RJD was defined as a positive answer by the investigator to the following question: “Do you consider that the patient has ever suffered from RJD (e.g. hip, shoulder) related to SpA?” In case of a positive answer, a potential specific treatment (e.g. Total Articular Replacement) was investigated. The patient’s characteristics were compared between those with and without RJD involvement, using Chi-2 or Fisher exact test for the categorical variables and t-test for the continuous variables. Two separate multivariable stepwise binary logistic regression analyses were conducted to identify factors associated with the dependent variables “hip involvement” and “shoulder involvement”.Results:RJD occurred in 1,503 patients (33.7%), with more prevalent hip (24.2%) than shoulder (13.2%) involvement. The prevalence of RJD as a group was the highest in Juv-SpA (52.7%), followed by pSpA (44.3%) and axSpA (33.9%). The highest prevalence of RJD was found in Asia and the lowest in Europe and North America. Among patients with hip involvement, 6.0% had a history of hip replacement (highest in the Middle East and North Africa and Latin America); among patients with shoulder involvement, 0.8% had a history of shoulder replacement. Hip had a distinct pattern of associations compared to shoulder involvement (Figure 1). Hip involvement was significantly associated with the SpA main diagnosis (highest in pSpA, lowest in PsA), younger age at first SpA symptom, lower prevalence of family history of psoriasis, positive HLA-B27, occiput-to-wall distance>0, and treatment with cs-DMARDs and b-DMARDs. Shoulder involvement was associated with the SpA main diagnosis (highest in Juv-SpA and pSpA, lowest in axSpA), older age at first SpA symptom, higher prevalence of enthesitis, dactylitis, tender joints count, IBD, occiput-to-wall distance>0, EQ5D score and treatment with cs-DMARDs.Conclusion:Hip involvement was more prevalent than shoulder involvement in patients with SpA, and had a distinct phenotype resembling axial disease whereas shoulder involvement was mostly associated with features of peripheral disease. Hip and shoulder involvement should be analyzed separately in future studies rather than under the RJD entity.References:[1]Lopez-medina, C. et al. Prevalence and Distribution of Peripheral Musculoskeletal Manifestations in Axial Spondyloarthritis, Peripheral Spondyloarthritis and Psoriatic Arthritis: Results of the International, Cross-sectional ASAS-PerSpA Study. RMD Open; 2021;7:e001450.Disclosure of Interests:None declared

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FRI0015 PHENOTYPE AND FUNCTION OF THE PERIPHERAL BLOOD DENDRITIC CELLS OF PSORIASIS PATIENTS WITH AND WITHOUT ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4296 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 578.1-579

Author(s):

S. Schnitte ◽

A. Fuchs ◽

T. Funk ◽

A. C. Pecher ◽

D. Dörfel ◽

...

Keyword(s):

Risk Factors ◽

Flow Cytometry ◽

Dendritic Cells ◽

Psoriatic Arthritis ◽

T Lymphocytes ◽

Peripheral Blood ◽

Surface Proteins ◽

Research Support ◽

Cross Sectional ◽

Cell Counts

Background:Psoriasis is a frequent skin disease that can appear with an arthritic manifestation in approximately 30% of the cases [1]. The underlying excessive immune reaction caused by pro-inflammatory cytokines can be triggered by several risk factors [2]. Various subgroups of Dendritic cells (DCs) in the skin play a crucial role in the induction of the dermal inflammatory response [3].Objectives:As the role of peripheral blood DCs remains unknown and the cause of an arthritic manifestation is still not completely understood [4], this project aimed to detect differences in phenotype or function of peripheral blood DCs in psoriatic patients with or without arthritis.Methods:We analyzed peripheral blood cells of 60 psoriasis patients with and without arthritis. Different DC subpopulations were detected by flow cytometry. Monocyte-derived DCs were cultured with or without Lipopolysaccharides to gain immature (iDC) and mature (mDC) cells. The DC phenotype was determined by staining with CD80, CD83, CD86, CD206, CCR7, CD1a, HLA-DR, CD40, GPN-MB, DC209 and CD14. Their T-cell stimulatory capability was analyzed by co-incubation with Carboxyfluorescein succinimidyl ester stained lymphocytes and the quantification of CD4+ T-lymphocytes afterwards. To measure the migration capacity DCs were seated into transwell chambers with a semipermeable membrane and partly supplemented with Macrophage Inflammatory Protein 3 Beta (Mip3b). Migrated cells were detected by flow cytometry. Measured cell counts were normalized to cell counts without Mip3b stimulation.Results:Comparing the factor of increase of migrated mDC counts due to mip3b stimulation, we detected a significant lower rate in samples of patients with arthritis (PsA) compared to those of patients without (Ps). Assays of mDCs without mip3b stimulation showed a significant higher count of migrated cells in the samples of the arthritic group [Figure 1]. Cell counts with Mip3b stimulation did vary slightly in the groups. The DC subpopulations and the expression of analyzed cell surface proteins did not show significant differences. The amounts of stimulated T-Lymphocytes did not differ significantly.Figure 1.Migration essay showing mDCs following Mip3b (+miß3b) as multiples of mDCs without stimulation (-mip3b). The factor of increase is significantly lower in patients with arthritis (PsA) compared to patients without (Ps). Absolute counts of migrated mDCs without Mip3b are significantly higher in the arthritic group. Cell counts with stimulation do not differ significantly (data not shown). N=24, p<0.05Conclusion:CCL19 (Mip3b) is a potent ligand to the CCR7 receptor inducing migration of DCs towards the lymphatic node [5]. The CCR7 amounts on the DC surface did not differ significantly in the groups. The mDCs without CCL19 stimulation migrated in higher amounts in samples of arthritic patients. Cell counts of stimulated DCs showed only slight differences. These results could be generated by a different appearance of the DCs of arthritic patients that might facilitate migration. Further experiments focusing on this aspect should be performed. A possible effect of disruptive factors (age, sex, medication…) needs to be clarified.References:[1]Henes, J.C., et al.,High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study.Rheumatol Int, 2014.34(2): p. 227-34.[2]Lee, E.B., et al.,Psoriasis risk factors and triggers.Cutis, 2018.102(5s): p. 18-20.[3]Kim, T.G., S.H. Kim, and M.G. Lee,The Origin of Skin Dendritic Cell Network and Its Role in Psoriasis.Int J Mol Sci, 2017.19(1).[4]Veale, D.J. and U. Fearon,The pathogenesis of psoriatic arthritis.Lancet, 2018.391(10136): p. 2273-2284.[5]Ricart, B.G., et al.,Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4.J Immunol, 2011.186(1): p. 53-61.Acknowledgments:This project was financially supported by Novartis Pharma GmbH.Disclosure of Interests:Sarah Schnitte Grant/research support from: Reaserch grant by Novartis, Alexander Fuchs: None declared, Tanja Funk: None declared, Ann-Christin Pecher: None declared, Daniela Dörfel: None declared, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,

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Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study

RMD Open ◽

10.1136/rmdopen-2020-001519 ◽

2021 ◽

Vol 7 (1) ◽

pp. e001519

Author(s):

Roberta Ramonda ◽

Mariagrazia Lorenzin ◽

Antonio Carriero ◽

Maria Sole Chimenti ◽

Raffaele Scarpa ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Adverse Events ◽

Disease Activity ◽

Biological Treatment ◽

Retention Rate ◽

Real Life ◽

Drug Retention ◽

Group A ◽

Group B ◽

Drug Retention Rate

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) diﬀerences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

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