Interstitial Lung Disease in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Initiating Biologics and Controls: Data From 5 Nordic Registries.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most common pulmonary manifestations of rheumatoid arthritis (RA), but its prevalence has not been investigated in psoriatic arthritis (PsA). The role of methotrexate (MTX) in ILD development remains under debate. This study (1) compares the incidences of ILD in patients with RA or PsA initiating a first biologic disease-modifying antirheumatic drug (bDMARD) to that in the general population, and (2) investigates the role of MTX comedication on ILD incidence. METHODS: Patients were identified in 5 rheumatology registries. Demographics, MTX use, and disease activity were retrieved. Matched subjects from the general population were available from 4 countries. Incidence of ILD during follow-up of up to 5 years was assessed through national patient registries. Subjects with prior ILD were excluded. Adjusted hazard ratios (HRs) were calculated for ILD incidence in patients vs the general population, and for MTX users vs nonusers. RESULTS: During follow-up of 29,478 patients with RA and 10,919 patients with PsA initiating a first bDMARD and 362,087 population subjects, 225, 23, and 251 cases of ILD were identified, respectively. HRs for ILD (vs population subjects) were 9.7 (95% CI 7.97-11.91) in RA and 4.4 (95% CI 2.83-6.97) in PsA. HRs for ILD with MTX comedication (vs nonuse) were 1.0 (95% CI 0.72-1.25) in RA and 0.9 (95% CI 0.38-2.05) in PsA. CONCLUSION: Among patients with RA and PsA initiating a bDMARD, the risk of ILD was higher than in the general population, and was highest in RA. MTX comedication was not a risk determinant for ILD.

Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries.

OBJECTIVES: To 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. METHODS: Observational 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. RESULTS: 24 083 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. CONCLUSION: The 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.

Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden.

OBJECTIVES: Pulmonary manifestations in RA are common comorbidities. Interstitial lung disease (ILD), both idiopathic and in RA, has been associated with several genetic variants. We assessed pulmonary fibrosis (PF) in an inception cohort of RA patients in relation to genetic variants and disease-related factors. METHODS: A total of 1466 early RA patients were consecutively included and followed prospectively from the index date until death or 31 December 2016. Clinical and laboratory data and treatment were continuously registered according to the Swedish Rheumatology Quality Register. DNA was available from 1184 patients and 571 151 genome-wide single-nucleotide polymorphisms (SNPs) were analysed. Thirteen identified genetic variants were extracted. At follow-up, the patients answered a questionnaire regarding disease progression and lung involvement that was validated by reviewing medical records and analysing radiological examinations. RESULTS: The prevalence of PF was 5.6% and the annualized incidence rate was 5.0/1000 (95% CI 3.80, 6.54). Four SNPs were associated with PF in RA: rs35705950 [MUC5B; OR 2.5 (95% CI 1.5, 4.0), adjusted P-value = 0.00016, q-value = 0.0021]; rs111521887 [TOLLIP; OR 1.9 (95% CI 1.3, 2.8), adjusted P-value = 0.0014, q-value = 0.0092]; rs2609255 [FAM13A; OR 1.7 (95% CI 1.1, 2.5), adjusted P-value = 0.013, q-value = 0.055] and rs2736100 [TERT; OR 1.5 (95% CI 1.0, 2.2), adjusted P-value = 0.046, q-value = 0.15]. Older age and RF positivity were associated with increased risk, while MTX treatment was associated with a lower risk of PF. CONCLUSIONS: Development of PF in an inception cohort of RA patients was associated with 4 of 12 ILD risk genes. RA-related factors except for age at diagnosis and RF positivity were of limited importance in PF development.

Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis.

OBJECTIVES: Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. METHODS: A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. RESULTS: In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60-75, fibrinogen (Fib)ß62-78 (72), Fibα621-635, Bla26, collagen (C)II359-369 and F4-CIT-R (P < 0.01 to P < 0.05). The number of ACPA specificities was also related to PF development (P < 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P < 0.05 in all models), anti-Vim60-75 (P < 0.05, in all models), anti-Fibß62-78 (72) (P < 0.001 to P < 0.05), anti-CII359-369 (P < 0.05 in all models) and anti-F4-CIT-R AQ4 (P < 0.01 to P < 0.05), anti-Fibα621-635 (P < 0.05 in one) and anti-Bla26 (P < 0.05 in two) were significantly associated with PF development. CONCLUSION: The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome.

OBJECTIVES: To investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA. METHODS: By linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996-2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations. RESULTS: We identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations. CONCLUSION: Siblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).

Mortality following new-onset Rheumatoid Arthritis: has modern Rheumatology had an impact?

OBJECTIVE: To investigate if, and when, patients diagnosed with rheumatoid arthritis (RA) in recent years are at increased risk of death. METHODS: Using an extensive register linkage, we designed a population-based nationwide cohort study in Sweden. Patients with new-onset RA from the Swedish Rheumatology Quality Register, and individually matched comparators from the general population were followed with respect to death, as captured by the total population register. RESULTS: 17 512 patients with new-onset RA between 1 January 1997 and 31 December 2014, and 78 847 matched general population comparator subjects were followed from RA diagnosis until death, emigration or 31 December 2015. There was a steady decrease in absolute mortality rates over calendar time, both in the RA cohort and in the general population. Although the relative risk of death in the RA cohort was not increased (HR=1.01, 95% CI 0.96 to 1.06), an excess mortality in the RA cohort was present 5 years after RA diagnosis (HR after 10 years since RA diagnosis=1.43 (95% CI 1.28 to 1.59)), across all calendar periods of RA diagnosis. Taking RA disease duration into account, there was no clear trend towards lower excess mortality for patients diagnosed more recently. CONCLUSIONS: Despite decreasing mortality rates, RA continues to be linked to an increased risk of death. Thus, despite advancements in RA management during recent years, increased efforts to prevent disease progression and comorbidity, from disease onset, are needed.

Acute coronary syndrome in new-onset rheumatoid arthritis: a population-based nationwide cohort study of time trends in risks and excess risks.

BACKGROUND: Acute coronary syndrome (ACS) and other cardiovascular diseases are the main drivers of the increased morbidity and preterm mortality in rheumatoid arthritis (RA). ACS in RA has been linked to inflammation and RA severity. During recent years and with new therapeutic options and treat-to-target strategies, increasing efforts have been made to reach RA remission as soon as possible after diagnosis, and the average level of RA disease activity has declined. Whether this has resulted in declining excess risks for RA comorbidities remains unclear. METHODS: We performed a nationwide population-based cohort study of patients with new-onset RA from 1997 to 2014, and matched general population comparators. In the Swedish healthcare system, all residents have equal access to healthcare services. Healthcare is monitored using high-quality population-based registers that can be linked together. 15 744 patients with new-onset RA, identified from the Swedish Rheumatology Quality Register, and 70 899 general population comparator subjects were included. RESULTS: Seven hundred and seventy two patients with RA developed an ACS during 103 835 person-years of follow-up (crude incidence, 7.4 per 1000), corresponding to an overall HR versus the general population of 1.41 (95% CI 1.29 to 1.54). Whereas the ACS incidence declined over calendar time in both the RA and the general population cohort, the excess and the relative risks of ACS remained the same. CONCLUSIONS: Despite improved disease control in new-onset RA, the elevated risk of ACS in RA remains a concern.

Response to biological treatment and subsequent risk of coronary events in rheumatoid arthritis.

OBJECTIVES: Whether the increased risk of comorbidities, such as cardiovascular disease, in rheumatoid arthritis (RA) can be reverted by particular antirheumatic therapies, or response to these, is unclear but of critical clinical importance. We wanted to investigate whether response to tumour necrosis factor inhibitors (TNFi) translates into a reduced risk for acute coronary syndrome (ACS). METHODS: A cohort of patients with RA initiating a first TNFi 2001-2012 was identified in the Swedish Biologics Register. The association between European League Against Rheumatism (EULAR) response after 3-8 months of treatment (assessed using the first, the best and the measurement closest to 5 months, respectively), and the risk of incident ACS during the subsequent year was analysed in Cox regression models. Adjustments included cardiovascular risk factors, joint surgery, RA duration, education and work disability. RESULTS: During 6592 person-years among TNFi initiators (n=6864, mean age 55 years, 77% women), 47 ACS occurred. The adjusted HRs (95% CI), which were similar to the crude HRs, of the 1-year risk of ACS among EULAR good responders compared with non-responders were 0.5 (0.2 to 1.4), 0.4 (0.2 to 0.9) and 0.5 (0.2 to 1.2), for the first, the best and the evaluation closest to 5 months, respectively. EULAR moderate responders had equal risk to that of EULAR non-responders, who, compared with the general population referents (n=34 229), had a more than twice the risk of ACS. For good responders, there was no statistically significant difference in risk versus the general population. CONCLUSIONS: Optimised RA disease control has the potential to revert otherwise increased risks for ACS in RA.

Incidence and predisposing factors of extra-articular manifestations in contemporary rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis [RA) is a chronic inflammatory disease, with potential for extra-articular manifestations (ExRA). The incidence and predisposing factors for ExRA and the mortality were evaluated in an early RA inception cohort. METHODS: Patients (n = 1468; 69 % females, mean age (SD) 57.3(16.3) years) were consecutively included at the date of diagnosis, between 1 January 1996 and 31 December 2016, and assessed prospectively. In December 2016 development of ExRA was evaluated by a patient questionnaire and a review of medical records. Cumulative incidence and incidence rates were compared between 5-year periods and between patients included before and after 1 January 2001. Cox proportional hazard regression models were used to identify predictors for ExRA, and models with ExRA as time-dependent variables to estimate the mortality. RESULTS: After a mean (SD) follow-up of 9.3(4.9) years, 238 cases (23.3 %) had ExRA and 151 (14.7 %) had ExRA without rheumatoid nodules. Most ExRA developed within 5 years from diagnosis. Rheumatoid nodules (10.5 %) and keratoconjunctivitis sicca (7.1 %) were the most frequent manifestations, followed by pulmonary fibrosis (6.1 %). The ExRA incidence among more recently diagnosed patients was similar as to the incidence among patients diagnosed before 2001. Seropositivity, smoking and early biological treatment were associated with development of ExRA. After 15 years 20 % had experienced ExRA. ExRA was associated with increased mortality, HR 3.029 (95 % CI 2.177-4.213). CONCLUSIONS: Early development of ExRA is frequent, particularly rheumatoid nodules. Predisposing factors were age, RF positivity, smoking and early biological treatment. The patients with ExRA had a 3-fold increase in mortality.

Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of ischemic heart disease, in both early and established RA. Data on the risk of ischemic heart disease in relation to therapy with tumor necrosis factor (TNF) antagonists (anti-TNF) are conflicting in patients with established RA and essentially lacking in those with early RA. In established RA, the risk of myocardial infarction has been linked to the response to anti-TNF therapies. The aim of this study was to determine the risk of acute coronary syndromes (ACS) in patients with early RA in relation to treatment with, and response to, anti-TNF. METHODS: A cohort consisting of patients in whom RA was diagnosed between 1999 and 2007 was identified from the Swedish Rheumatology Register (n=6,000), from which information on disease activity and pharmacologic treatments was extracted. In a cohort study, the risk of first occurrence of an ACS was compared between patients treated with anti-TNF and those without exposure to anti-TNF, using hazard ratios (HRs). In a nested case-control study, the relationship between response to anti-TNF according to the European League Against Rheumatism (EULAR) response criteria and the risk of ACS was investigated. RESULTS: In the cohort study, treatment with anti-TNF was not related to any statistically significant alteration in the risk of ACS (HR 0.80, 95% confidence interval [95% CI] 0.52-1.24). In the nested case-control study, a good or moderate EULAR treatment response at 3 months and at 6 months was not associated with a risk of ACS (odds ratio [OR] 1.7, 95% CI 0.5-5.1 and OR 1.5, 95% CI 0.3-6.9, respectively), when adjusted for disease activity before treatment start. CONCLUSION: In this study of patients treated with anti-TNF within the first years of RA, neither treatment with, nor response to, anti-TNF therapy could be linked to any statistically significant decrease in the risk of ACS.

Time Trends of Cardiovascular Disease in the General Population and Inflammatory Arthritis.

Cardiovascular diseases (CVDs) are the leading causes of death in the world, but declining trends for cardiovascular (CV) mortality and morbidity have been observed during the last decades. Reports on secular trends regarding the excess CV mortality and morbidity in rheumatoid arthritis show diverging results. Data support that also patients with inflammatory arthritis have benefited from improved treatment and prevention for CVD, which can be observed, for example, in decreased case fatality after CV event. However, several recent studies indicate a remaining excess CV risk in patients with inflammatory arthritis.

Individual Regression Modeling of Spinal Mobility Measurements in Long-Term Ankylosing Spondylitis: In-Depth Analyses With Comparison to Norm Data.

OBJECTIVE: Normal age-related decline and temporary restrictions in mobility complicate the understanding of spinal mobility deterioration over time in patients with ankylosing spondylitis (AS). In this study, we aimed to determine whether spinal mobility deterioration occurred linearly in patients with AS. We also aimed to compare patterns of change with corresponding age-related normal values and analyze variations in temporary fluctuations in mobility measurements over time. METHODS: We included 111 men and 30 women (median age 20.9 years at symptom onset), who were followed for a median of 34 years since symptom onset. This inclusion resulted in 9,697 spinal mobility measurements for analysis. Individual linear regression models for development of lateral spinal flexion (LSF), the 10-cm Schober test (ST10), chest expansion (CE), and cervical rotation (CR) were analyzed and compared with normal age-related decline over time. RESULTS: The median values for the constants of all measurements were significantly lower than the norm data. However, LSF, ST10, and CE followed a yearly linear decline comparable to the norm data, whereas CR declined approximately twice as fast as expected from the norm data (beta median -0.62° [25th-75th percentile -1.16, -0.22] and -0.35° [25th-75th percentile -0.35, -0.35], respectively). Temporary fluctuations in LSF and CE were significantly higher during the early phase of the disease, with decreasing residuals over time. CONCLUSION: Based on median constants of our data, mobility restrictions related to AS seem to mainly occur during the first years of disease, indicating a narrow window of opportunity for prevention.

How does current disease activity in rheumatoid arthritis affect the short-term risk of acute coronary syndrome? A clinical register based study from Sweden and Norway.

OBJECTIVES: To estimate short-term risks of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) as a function of current RA disease activity including remission. METHODS: Data from clinical visits of RA patients in Sweden (SE) and Norway (NO) between January 1st 2012 until December 31st 2020 were used. At each visit, patient's disease activity was assessed including remission status (measured with several metrics). Through linkage to national health and death registers, patients were followed up for incident ACS up to six months from each visit. We compared the short-term risk of ACS in patients not in remission vs. in remission using Cox regression analyses with robust standard errors, adjusted for country and covariates (e.g., age, sex, prednisolone use, comorbidities). We also explored disease activity categories as exposure. RESULTS: We included 212,493 visits (10,444 from Norway and 202,049 from Sweden) among 41,250 patients (72% women, mean age at visit 62 years). During the 6-month follow-ups, we observed 524 incident ACS events. Compared to patients in remission, patients currently not in remission had an increased rate of ACS: adjusted hazard ratio (95% confidence interval) 1.52 (1.24-1.85) with DAS28 metric. The crude absolute six-month risks were 0.2% for patients in remission vs. 0.4% for patients with DAS28 high disease activity. The use of alternative RA disease activity and remission metrics provided similar results. CONCLUSION: Failure to reach remission is associated with elevated short-term risks of ACS, underscoring the need for CV risk factor optimization in these patients.

Commonalities and differences in set-up and data collection across European spondyloarthritis registries - results from the EuroSpA collaboration.

BACKGROUND: In European axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) clinical registries, we aimed to investigate commonalities and differences in (1) set-up, clinical data collection; (2) data availability and completeness; and (3) wording, recall period, and scale used for selected patient-reported outcome measures (PROMs). METHODS: Data was obtained as part of the EuroSpA Research Collaboration Network and consisted of (1) an online survey and follow-up interview, (2) upload of real-world data, and (3) selected PROMs included in the online survey. RESULTS: Fifteen registries participated, contributing 33,948 patients (axSpA: 21,330 (63%), PsA: 12,618 (37%)). The reported coverage of eligible patients ranged from 0.5 to 100%. Information on age, sex, biological/targeted synthetic disease-modifying anti-rheumatic drug treatment, disease duration, and C-reactive protein was available in all registries with data completeness between 85% and 100%. All PROMs (Bath Ankylosing Spondylitis Disease Activity and Functional Indices, Health Assessment Questionnaire, and patient global, pain and fatigue assessments) were more complete after 2015 (68-86%) compared to prior (50-79%). Patient global, pain and fatigue assessments showed heterogeneity between registries in terms of wording, recall periods, and scale. CONCLUSION: Important heterogeneity in registry design and data collection across fifteen European axSpA and PsA registries was observed. Several core measures were widely available, and an increase in data completeness of PROMs in recent years was identified. This study might serve as a basis for examining how differences in data collection across registries may impact the results of collaborative research in the future.

Neither low social support nor low decision latitude at work is associated with disease remission among patients with rheumatoid arthritis: results from the Swedish EIRA study.

OBJECTIVES: To investigate the association between psychosocial vulnerability, defined as either low social support or low decision latitude at work, and disease remission at 3, 12, and 60 months in patients with rheumatoid arthritis (RA). METHODS: This cohort study included all patients enrolled in both the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) 1996-2015 and the Swedish Rheumatology Quality Register (SRQ, n = 2820). Information on social support and decision latitude at work at RA diagnosis were identified from the EIRA questionnaire. Indexes for levels of social support and decision latitude at work, respectively, were calculated based on the questionnaire. Low social support and low decision latitude at work, respectively, were identified by a score in the lowest quartile and compared with the three other quartiles (not low). Disease-activity parameters were retrieved from SRQ at 3, 12, and 60 months. The associations between social support or decision latitude at work, respectively, and Disease Activity Score 28 joint count with C-reactive protein (DAS28-CRP) remission were analysed using logistic regression models adjusted for age, sex, smoking habits, alcohol habits, symptom duration, and educational level. RESULTS: Having low social support (n = 591) was not associated with DAS28-CRP remission at 3 (OR 0.93, 95% CI 0.74-1.16), 12 (OR 0.96, 95%CI 0.75-1.23), or 60 (OR 0.89, 95%CI 0.72-1.10) months compared to not low social support (n = 2209). No association was observed for low (n = 212) versus not low (n = 635) decision latitude at work and DAS28-CRP remission at 3 (OR 0.84, 95%CI 0.54-1.31), 12 (OR 0.81, 95%CI 0.56-1.16), or 60 (OR 1.37, 95%CI 0.94-2.01) months. CONCLUSION: In a country with general access to healthcare, psychosocial vulnerability does not influence the likelihood of achieving remission in early RA.

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study.

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 µg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology.