Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany

Objective Data on uveitis in juvenile psoriatic arthritis (JPsA), a category of juvenile idiopathic arthritis (JIA), are scarce. We describe prevalence and risk factors for JPsA-associated uveitis (JPsA-U). Methods Cross-sectional data from the National Pediatric Rheumatological Database (from 2002 to 2014) were used to characterize JPsA-U and assess risk factors for uveitis development. Results Uveitis developed in 6.6% of 1862 JPsA patients. JPsA-U patients were more frequently female (73.0 vs 62.9%, p=0.031), ANA positive (60.3 vs 37.0%, p<0.001), younger at JPsA onset (5.3 ± 4.1 vs 9.3 ± 4.4 years, p<0.001), and received DMARD (disease modifying antirheumatic drug) treatment significantly more frequently than JPsA patients without uveitis. On multivariable analysis of a subgroup of 655 patients, mean cJADAS during study documentation was significantly associated with uveitis development. Children with early onset of JPsA were significantly more frequently ANA positive (48.4% vs 35.7% for those younger than 5 years at JPsA onset versus those aged 5 years and older, p<0.001), less often affected by skin disease (55.3% vs 61.0%, p=0.032), but more frequently by uveitis (17.3% vs 3.8%, p<0.001), and required DMARD treatment more frequently (52.9% vs 43.8%, p<0.001). Conclusion The characteristics of JPsA patients developing uveitis are similar to those of patients with uveitis in other JIA categories, such as oligoarticular JIA. Especially those children with early onset of JPsA seem to be at a higher risk for ocular involvement. Our data support the notion of a major clinical difference between those patients with early versus late onset of JPsA.

Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases—An Interim Report from a Danish Prospective Cohort Study

Background/Purpose: In light of the current COVID-19 pandemic, whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease-modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV-2 vaccinations remains a major concern. There is an urgent need for more SARS-CoV-2 vaccine efficacy data to inform healthcare providers on the potential need for a booster vaccine. We established the ‘Detection of SARS-CoV-2 antibodies in Danish Inflammatory Rheumatic Outpatients’ study (DECODIR) in March 2021 in order to assess and compare the immunoglobulin G (IgG response) of the SARS-CoV-2 BNT162b2 vaccine (Pfizer, Groton, CT, USA/BioNTech, Mainz, Germany) and mRNA-1273 vaccine (Moderna, Cambridge, MA, USA) administered as part of the national vaccine roll out in patients with RMDs, irrespective of treatment. Patients’ SARS-CoV-2 IgG level was used as proxy to determine vaccination response. Methods: The study is a longitudinal prospective cohort study in which the SARS-CoV-2 antibody response was measured and compared at baseline and at six weeks following vaccination. The study population consisted of patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA), or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg. Bloods, patient reported outcome measurements (PROMS), clinical data, and treatment information (cs/bcs/bDMARD) were collected at baseline/6 weeks and documented in the Danish DANBIO registry. Commercially available antibody tests (ThermoFisher, Waltham, MA, USA) were used, and SARS-CoV-2 IgG levels were reported in EliA U/mL. Sufficient IgG response was defined as ≥10 EliA U/mL (manufacturers cut-off). Associations between antibody response, age, gender, disease (RA/PsA/SpA), no treatment or cs/bDMARD treatment, and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR), and bootstrapped 95% confidence interval (CI) of the median. Results: A total of 243 patients were included. We observed a significant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 34.5 EliA U/mL at 6 weeks). Seventy-two patients (32%) had an insufficient IgG response. The median IgG level in patients treated with cs/bcs/bDMARD combination therapy was significantly lower compared to patients without any DMARD treatment (12 EliA U/mL vs. 92 EilA U/mL (p < 0.01)). Conclusion: Patients treated with a combination of cs/bcs/bDMARD are at significantly higher risk of an inadequate response to SARS-CoV-2 vaccines as measured by IgG level compared to patients without DMARD treatment. IgG SARS-CoV-2 are only part of the immune response, and further data are urgently needed. At present, our results may inform healthcare providers and policy makers on the decision for the need of a booster vaccine in this particular patient group.

Assessment of the Ovarian Reserve by Serum Anti-Müllerian Hormone in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> The ovarian reserve has been reported to be diminished in patients with rheumatoid arthritis. However, these results are still controversial. Anti-Müllerian hormone (AMH) is considered a reliable biomarker for the ovarian reserve. We thus performed a meta-analysis to evaluate the AMH levels and the effect of DMARDs on the ovarian reserve in rheumatoid arthritis patients. <b><i>Methods:</i></b> PubMed, EMBASE, the Cochrane Library, and 2 Chinese databases (CNKI and Wanfang database), up to September 2021, were searched for relevant studies. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Pooled standard mean difference (SMD) with 95% confidence intervals (CIs) were determined with the random-effects model. The heterogeneity was described by <i>I</i>^<i>2</i> statistic and <i>p</i> value from the Cochrane Q test. <b><i>Results:</i></b> Eight eligible studies (679 patients and 1,460 controls) were included in the meta-analysis. Compared with healthy control, the AMH levels in RA patients were significantly lower with the pooled SMD of −0.40 (95% CI: −0.66 to −0.14). However, in comparison of AMH with and without DMARD treatment, there was no significant difference with the pooled SMD of −0.1 (95% CI: −0.39 to 0.19). <b><i>Conclusion:</i></b> The results indicated that there was an increased risk of ovarian failure in RA patients and which is not related to DMARD treatment.

Juvenile Idiopathic Arthritis and COVID-19 Pandemic: Good Compliance With Treatment, Reluctance to Return to School

Objective: The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. After national lockdowns, many patients were also concerned about their safety at school. We evaluated the impact of the pandemic on the optimal continuation of treatment and on the return to school in JIA patients.Methods: JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. The primary outcome was DMARD treatment modification in relation to the context of the pandemic but we also evaluated the pandemic's impact on the schooling.Results: One hundred and seventy three patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases. Two patients were diagnosed positive for SARS-CoV-2 infection.Conclusion: This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic and were rarely affected by symptomatic COVID-19. In contrast, parents' reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.

A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis

Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1β, SAA1γ, SAA2α, and SAA2β) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patients, and SAA2α appears to mostly mediate the pathological role of A-SAA. Levels of these variants, together with SAA1β, only decreased under biologic DMARD treatment but not under methotrexate monotherapy. This study highlights the importance to better understand the modulation of expression of these variants in ERA in order to subsequently better characterize their biological function. On the other hand, alarmin expression increased in ERA compared to controls but remained elevated after 12 months of methotrexate or biologic treatment. The work overcomes the concept of considering these proteins as biomarkers for diagnosis, demonstrating that SAA1α, SAA1β, and SAA2α variants but also S100A8 and S100A9 do not respond to all early treatment in ERA and should be rather considered as companion markers useful to improve the follow-up of treatment response and remission state. Moreover, it suggests that earlier use of biologics in addition to methotrexate may be worth considering.

POS1398 RHEUMATOLOGICAL PATIENTS PERFORMING BLOOD SELF-SAMPLING FOR DMARD THERAPY SAFETY: A PROOF OF CONCEPT STUDY COMPARING WITH VENOUS BLOOD SAMPLES

Background:Regular blood sampling is a requirement for rheumatological patients receiving csDMARD, bDMARD or tsDMARD therapies (1). The frequent blood sampling affects the patient’s life as they use a substantial amount of time at hospitals or by the general practitioner. Often visits are time-consuming with transport, waiting time, and for some patient’s costly long travels. Giving patients the option of taking the blood samples themself in their own home, as part of a patient-centred monitoring approach, could provide the patient much higher degree of independence. Further, it may increase the quality of life, cause higher compliance with taking the control samples and possibly reduce health care costs.Objectives:1. To investigate if rheumatological patients can take capillary blood samples and describe patient-reported outcomes (PRO) about the procedure. 2. Compare the venous and capillary samples’ results. 3. Test if the laboratory automated analysis equipment can handle the small capillary samples.Methods:21 rheumatological patients, underwent capillary and venous blood sampling at up to 4 occasions (1-2 months between). Instructions were available on a pictogram. PRO data were assessed by questionnaires. The patient performed blood extraction to the capillary samples from a finger after using a device making a small incision (2 mm depth and 3 mm width). Two capillary tubes (one Microtainer K2-EDTA and one Microtainer lithium heparin with gel) were filled with a total volume of approximately 1.0 mL blood. A phlebotomist took the venous sample. Blood samples were analyzed for alanine aminotransferase (ALAT), albumin, alkaline phosphatase (ALP), calcium, C-reactive protein (CRP), creatinine, potassium, lactate dehydrogenase (LDH), urate, hemolysis index, erythrocyte corpuscular volume (MCV), haemoglobin, leukocytes, differential count and platelets.Results:A total of 53 paired capillary (C) and venous (V) samples were taken. The average perceived pain of the procedure of C sampling was VAS: 10.3 (SD:14.4) (0-100) versus V sampling VAS: 8.5 (SD:11.7). 90% of patients would accept it as a future form of blood sampling.Differences in blood samples (C versus V) were: CRP (-3.4%); Hemoglobin (-1.4%); Creatinine (-4.4%), ALAT (-2.9%), neutrophils (1.43%), platelets (-16.9%).The index of hemolysis was on average 128.9 mg/dL (SD: 203) in C versus 6.7 mg/dL (SD: 4.6) in V. Results was evaluated by a rheumatologist, and 92.5% of capillary samples could be used to evaluate the safety of DMARD treatment based on the most critical samples for this: ALAT, creatinine, neutrophils and platelets (1). The 7.5 % not accepted were all due to aggregated platelets leading to low platelet count. There was hemolysis in 18% of the samples, but the analysis results could be used despite this.Conclusion:In the majority of rheumatological patients, capillary self-sampling is well tolerated.We show that it is possible to extract the needed results from the capillary samples to evaluate DMARD treatment safety, despite higher hemolysis index. Using capillary samples taken at home could be a central instrument in future rheumatological patient-centred monitoring.References:[1]Rigby WFC et al. Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs. Int J Rheumatol. 2017Disclosure of Interests:None declared

POS1314 JUVENILE IDIOPATHIC ARTHRITIS IN THE CONTEXT OF THE CORONAVIRUS DISEASE 19 PANDEMIC: IMPACT ON THE DECREASE IN TREATMENT AND THE RETURN TO SCHOOL

Background:The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. In France, after the first lockdown from March to May 2020, many parents and children were then also concerned about whether reopening plans for school could ensure the safety of students, despite data concerning children with COVID-19 seem reassuring, and very few of them develop severe forms of the disease (1, 2, 3).Objectives:Our objectives were to evaluate the impact of the COVID-19 pandemic on the therapeutic management of JIA, the frequency of returning to school after the first lockdown period and the prevalence of SARS-CoV-2 infection at the time of the survey.Methods:JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. Data regarding the general characteristics of the participants, medical history, SARS-CoV-2 infection, characteristics of JIA subtypes and treatment modifications were collected.Results:A total of 173 patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants, our results reflect good adherence of the patient/parents to their immunosuppressive treatments. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases, due to anxiety of the patient/parents regarding COVID-19. Two patients were diagnosed positive for SARS-CoV-2 infection.Conclusion:This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic. In contrast, parents’ reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.References:[1]Filocamo G, et al. “Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs.” J Rheumatol. 25 avr 2020;[2]Tagarro A, et al. “Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain.” JAMA Pediatr. 8 avr 2020;[3]Lu X, et al. « SARS-CoV-2 Infection in Children”. N Engl J Med. 23 avr 2020;382(17):1663-5.Acknowledgements:We would like to thank all the participants involved in this clinical research and six medical students who helped completing the forms: Margaux Blondel, Alice Bonnod, Marie Desval, Béatrice Dordain, Gabrielle Fagnet, and Madouc De Saint Martin Pernot.Disclosure of Interests:None declared

AB0258 DMARD-TREATMENT OF UNDIFFERENTIATED ARTHRITIS INTENSIFIED DURING THE LAST DECENNIA, BUT DID NOT RESULT IN IMPROVED LONG TERM OUTCOMES

Background:EULAR guidelines stress timely initiation of DMARD-treatment in early arthritis patients also when classification criteria are not yet fulfilled. Consequently, undifferentiated arthritis (UA) patients may be increasingly treated with disease modifying antirheumatic drugs (DMARDs), despite inadequate placebo-controlled evidence for its effectivity. Implementation of this guideline also hampers future placebo-controlled trials in UA. However, historical data, with inclusion period as instrumental variable, can provide insight whether long term outcome is improved with increased DMARD-use, and thus serve to investigate if DMARD-treatment is effective in UA.Objectives:With 25-years of observational data of newly referred UA-patients, we studied whether enhanced treatment strategies resulted in better long term outcomes for UA.Methods:Between 1993 and 2019, 1132 consecutive UA-patients, not fulfilling the 1987/2010 criteria for RA or any other distinct diagnosis, were included in the Leiden Early Arthritis Cohort; patients were divided in 5 inclusion periods (1993-1998, 1999-2005, 2006-2010, 2011-2014, 2015-2019). Frequency of DMARD-initiation after diagnosis was compared. We studied the following outcomes: the course of disease activity scores (DAS28-CRP) and Health assessment questionnaires (HAQ), progression to RA after 1-year (according to the 1987 and/or 2010 criteria) and the frequency of prolonged DMARD-free status within 10-years of follow-up (this was defined as either spontaneous remission or sustained remission after discontinuation of DMARD-treatment).Results:The current population of UA-patients, thus not fulfilling 1987 or 2010 criteria, had rather mild disease: the median SJC was 1, the median TJC 2, 95% was autoantibody-negative and the median HAQ was 0.6. These characteristics were similar in the different inclusion periods. Initiation of DMARD-treatment in UA increased over time: 18%, 35%, 38%, 43% up to 55% in respectively 1993-1998, 1999-2005, 2006-2010, 2011-2014 and 2015-2019, in which methotrexate became more common in the last decade. Frequency of progression to RA after 1-year did not decrease and was 14%, 21%, 26%, 19% and 28% in the respective inclusion periods. Long-term DAS28CRP-scores improved from 2011 onwards (range -0.18, -0.24; p<0.05). However HAQ-score over time did not improve compared to the 1993-1998 period (range -0.00, -0.08; p>0.05). Also the percentages of patients in DMARD-free status after 10-years of follow-up did not significantly improve over time: 57%, 58%, 59% (for 1993-1998, 1999-2005, 2006-2010 respectively, p=0.59).Conclusion:Intensified DMARD-treatment of patients with UA did not result in improved outcomes. These data may indicate overtreatment of UA-patients. Yet, methods to stratify which UA-patients should be treated remains warranted.Disclosure of Interests:None declared

POS1207 REAL WORLD POPULATION-BASED ASSESSMENT OF COVID-19 OUTCOMES AMONG RHEUMATOID ARTHRITIS PATIENTS USING BIOLOGIC OR SYNTHETIC DMARDs

Background:While some risk factors for severe COVID have been identified for patients with rheumatic diseases,1 few studies have investigated whether outcomes differ based on the type of rheumatoid arthritis (RA) treatment. Most existing reports have been limited to individual centers or voluntary reporting registries.2,3Objectives:To compare the occurrence of hospitalizations following COVID-19 diagnosis among patients with RA treated with various classes of DMARDs.Methods:A cohort of patients with confirmed COVID-19 (ICD10 diagnosis code or positive PCR or antigen test result) were identified within a large US electronic health record (EHR) dataset (Optum, Inc.) during the time period Feb 1, 2020 through Oct 14, 2020. From these, we identified RA patients (ICD10 RA diagnosis code) with treatment (most recent of JAK inhibitor [JAKi], biologic [bDMARD] or conventional synthetic [csDMARD] only) within the 12 months prior to COVID-19 diagnosis (i.e., index). The primary outcome was any hospitalization on or within 30 days after COVID-19 diagnosis. Multivariable logistic regression models compared users of JAKi’s to non-TNFi bDMARDs and csDMARDs (separately), as well as users of TNFi’s to non-TNFi bDMARDS and csDMARDs (separately), and were adjusted for age, gender, index month and baseline corticosteroid use. Sensitivity analyses included restriction of prevalent treatment use to within 180 days prior to COVID-19 diagnosis and restriction of csDMARDs to a group without hydroxychloroquine or chloroquine.Results:The study included 910 RA patients on DMARD treatment who were diagnosed with COVID-19 (mean age ± SD: 61±15, 80% female, 62% white. Of those, 26% (n=240) were hospitalized on or within 30 days after COVID-19 diagnosis. The proportion of patients hospitalized was highest in non-TNFi bDMARD users (37/87; 43%), followed by csDMARDs users (161/581; 28%) and lowest in JAKi (13/68; 19%) and TNFi users (29/174; 17%). In multivariable-adjusted models, no differences in risk of hospitalization were found comparing JAKi users to csDMARD users (aOR=0.71; 95% CI 0.37-1.36) or TNFi users to csDMARD users (aOR=0.67; 95%CI 0.43-1.06). Compared to non-TNFi bDMARD users, JAKi use and TNFi use was associated with reduced risk of hospitalization (JAKi aOR=0.32; 95%CI 0.14-0.71; TNFi aOR=0.34; 95%CI 0.18-0.62). Age and corticosteroid use were positively associated with 30-day hospitalization in all models. Results of sensitivity analyses were consistent with the main findings.Conclusion:In this study, roughly a quarter of RA patients with recent DMARD treatment were hospitalized within 30 days after COVID diagnosis. Patients treated with JAKi and TNFi therapies experienced the lowest risk of hospitalization, with risk of hospitalization significantly lower than non-TNFi bDMARDs. However, recent therapy recorded in the EHR may not reflect exposure at time of COVID-19 diagnosis and small sample size per treatment may limit interpretation.References:[1]Hyrich KL, Machado PM. Nat Rev Rheumatol 2020;1-2. doi:10.1038/s41584-020-00562-2[2]Gianfrancesco MA, et al. Lancet Rheumatol 2020;2(5):e250-e253. doi:10.1016/S2665-9913(20)30095-3[3]Veenstra J, et al. J Am Acad Dermatol 2020;83(6):1696-1703.Acknowledgements:Jonathan Johnson of Optum, Inc. provided dataset guidance and conducted data analyses. AbbVie funded this study, contributed to its design, participated in data collection, analysis, and interpretation of the data, and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship.Disclosure of Interests:Lani Wegrzyn Shareholder of: AbbVie, Employee of: AbbVie, Kevin Winthrop Consultant of: Pfizer, AbbVie, UCB, Eli Lilly & Company, Galapagos, GSK, Roche, Gilead, BMS, Regeneron, Sanofi, AstraZeneca, Novartis, Grant/research support from: BMS, Pfizer, Seoyoung Kim Grant/research support from: institutional research grants from Pfizer, AbbVie, Roche, BMS for unrelated studies, Yizhou Ye Shareholder of: AbbVie, Employee of: AbbVie, Carrie Huisingh Shareholder of: AbbVie, Employee of: AbbVie, Whitney Krueger Shareholder of: AbbVie, Employee of: AbbVie, anna maniccia Shareholder of: AbbVie, Employee of: AbbVie, Ryan Kilpatrick Shareholder of: AbbVie, Employee of: AbbVie.

The association between increased body mass index and response to conventional synthetic DMARD treatment in rheumatoid arthritis: Results from the METEOR database

Background Few data exist on the association between increased BMI and response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). We aimed to explore the association between increased (overweight or obese) BMI on csDMARD-prescribing, methotrexate-dose and disease activity over 12-months. Methods Participants in an international RA database were stratified into early (&lt;1year post-diagnosis) and established RA. EULAR response, DAS28 remission and treatments were recorded at baseline, 6-months and 12-months. Increased BMI was explored in early and established RA, as predictors of good EULAR response, DAS28 remission, number of csDMARDs and methotrexate-dose, using logistic and linear regression. Results Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs, compared with normal BMI. In patients taking methotrexate, overweight and obese patients with early and established RA were exposed to higher methotrexate doses (mono- and combination-therapy), with a mean dose of 20mg/week, compared to 15mg/week in those of normal BMI. Conclusion We observed, compared to patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimisation of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.