Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study.

OBJECTIVES: To compare all-cause mortality and causes of death between patients with psoriatic arthritis (PsA) and the general population in Sweden. METHODS: Adults with at least one main PsA diagnosis (International Classification of Diseases-10: L40.5/M07.0-M07.3) from outpatient rheumatology/internal medicine departments 2001-2017 were identified from the National Patient Register. Each case was matched to five population comparator-subjects on sex/county/age at the case's first arthritis diagnosis. Follow-up ran from 1 January 2007, or from first PsA diagnosis thereafter, until death, emigration or 31 December 2018. Mortality was assessed overall, and stratified by sex and duration since diagnosis (diagnosis before/after 1 January 2007), using matched Cox proportional hazard regression (excluding/including adjustments for comorbidity) or Breslow test, as appropriate. Incidence rate ratios (IRR) of death, overall and stratified by sex/duration since diagnosis/age, as well as causes of death in PsA cases and comparator-subjects were also described. RESULTS: All-cause mortality was elevated in PsA (HR: 1.11 (95% CI: 1.07 to 1.16); IRR: 1.18 (95% CI: 1.13 to 1.22)), mainly driven by increased risks in women (HR: 1.23 (95% CI: 1.16 to 1.30)) and cases with longer time since diagnosis (HR: 1.18 (95% CI: 1.12 to 1.25)). IRR of death were significantly increased for all ages except below 40 years, with the numerically highest point-estimates for ages 40-59 years. When adjusted for comorbidity, however, the elevated mortality risk in PsA disappeared. Causes of death were similar among PsA cases/comparator-subjects, with cardiovascular disease and malignancy as the leading causes. CONCLUSIONS: Mortality risk in PsA in Sweden was about 10% higher than in the general population, driven by excess comorbidity and with increased risks mainly in women and patients with longer disease duration.

Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients.

OBJECTIVE: To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA. METHODS: A cohort of 275 patients with early RA, recruited in 2012-2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0-100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis. RESULTS: After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures. CONCLUSION: A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA.

Adherence to dietary guidelines, and the risk of developing rheumatoid arthritis: results from a nested case-control study.

OBJECTIVES: To examine the relationship between adherence to dietary guidelines and the risk of developing RA. METHODS: Participants in the Malmö Diet and Cancer Study (MDCS) cohort diagnosed with RA were identified through register linkage and validated in a structured review. Four controls per case were selected, matched for sex, year of birth, and year of inclusion in the MDCS. Diet was assessed at baseline (1991-1996) using a validated diet history method. A Diet Quality Index (DQI) based on adherence to the Swedish dietary guidelines including intakes of fibre, vegetables and fruits, fish and shellfish, saturated fat, polyunsaturated fat, and sucrose, was used. The associations between the DQI and its components and the risk of RA were assessed using conditional logistic regression analysis, adjusting for total energy intake, smoking, leisure time physical activity and alcohol consumption. RESULTS: We identified 172 validated cases of incident RA in the cohort. Overall adherence to the dietary guidelines was not associated with the risk of RA. Adherence to recommended fibre intake was associated with decreased risk of RA in crude and multivariable-adjusted analyses, with odds ratios (ORs) 0.60 (95% CI 0.39, 0.93) and 0.51 (95% CI 0.29, 0.90), respectively, compared with subjects with non-adherence. CONCLUSIONS: Reaching the recommended intake level of dietary fibre, but not overall diet quality, was independently associated with decreased risk of RA. Further studies are needed to assess the role of different food sources of dietary fibre in relation to risk of RA and the underlying mechanisms.

Associations between plasma metabolism associated proteins and future development of giant cell arteritis: results from a prospective study.

OBJECTIVE: To investigate the relation between biomarkers associated with metabolism and subsequent development of giant cell arteritis (GCA). METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), who were subsequently diagnosed with GCA, were identified in a structured process. Matched GCA-free controls were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. RESULTS: There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, Adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated (odds ratio (OR) per standard deviation (SD) 1.67; 95% CI 1.08-2.57), and Fructose-1,6-bisphosphatase 1 (FBP1) negatively associated (OR per SD 0.59; 95% CI 0.35-0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those sampled closest to diagnosis with a decreasing trend with longer time to GCA (p= 0.03). In the hypothesis generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. CONCLUSION: Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.

Circulating Interleukin 17A and Other Inflammatory Proteins May Predict Cardiovascular Disease in Early Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early rheumatoid arthritis (RA). METHODS: This study included consecutive patients with early RA recruited between 1995 and 2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were predesignated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (ie, factor loading > 0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. RESULTS: Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of interleukin 17A (IL-17A) were associated with CVD (hazard ratio 1.35, 95% CI 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking, and erythrocyte sedimentation rate [ESR]), although not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes, but only in crude models. No associations were observed for IL-6, tumor necrosis factor, monocyte chemotactic protein-1, or IL-8. In the exploratory analyses, MCP-3 in particular had significant associations with both outcomes in crude models. CONCLUSION: Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude the possibility that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Further, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA.

Disability Related to the Upper Extremities in Early Rheumatoid Arthritis - Long-term Course and Disease Parameter Impact: a cohort study.

OBJECTIVE: To investigate the course of disability related to the upper extremities (UE) in early rheumatoid arthritis (RA), and to assess correlations between such disability and clinical parameters, including grip force. METHODS: In an inception cohort of patients with early RA (diagnosed 1995-2005, N=222, follow-up 10 years), disability of the UE was assessed using a subscore of the Health assessment questionnaire disability index (HAQ-DI), and average grip force of the dominant hand was measured. Changes between consecutive follow-up visits in the HAQ-DI-UE subscore, and correlations at each visit with key clinical parameters, were assessed. The relation between joint involvement and HAQ-DI-UE was examined using multivariate linear regression analysis. RESULTS: The HAQ-DI-UE decreased significantly from inclusion to the 6-month follow-up (mean change -0.26; 95% CI -0.18 to -0.34), and increased significantly after 2 years. There were fairly strong correlations for HAQ-DI-UE with grip force (r:-0.50 to -0.62), patient's global assessment (r: 0.58 to 0.64) and patient's assessment of pain (r:0.54 to 0.60) at all time points through 5 years, but only moderate to weak correlations with swollen joints, CRP and ESR. At inclusion wrist synovitis and tender proximal interphalangeal (PIP) joints had both an independent impact on HAQ-DI-UE, whereas tenderness of the shoulder and the wrist had a greater importance at 6 months. CONCLUSION: Disability related to the upper extremities decreased significantly during the first 6 months, and increased again after 2 years. The correlations with clinical parameters underline the major impact of pain and impaired hand function in early RA.

Incidence of Clinically Diagnosed Psoriatic Arthritis in Sweden.

OBJECTIVE: Prior incidence estimates of psoriatic arthritis (PsA) vary considerably. We aimed to assess the annual incidence of clinically diagnosed PsA among adults in Sweden in 2014-2016, overall and stratified by age/sex/education/geography, and to investigate potential time trends in incidence in 2006-2018. Use of disease-modifying antirheumatic drugs (DMARDs) during the 2 years after diagnosis was also examined. METHODS: Patients (aged ≥ 18 years) with incident clinically diagnosed PsA in Sweden were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). Population statistics, stratification variables, and DMARD information were retrieved from other nationwide registers. Incidence was estimated according to a base case (BC) definition (ie, ≥ 1 main International Classification of Diseases, 10th revision, diagnosis of PsA [L40.5/M07.0-M07.3] from rheumatology/internal medicine in NPR, or a PsA diagnosis in SRQ during the relevant year, and no prior such diagnoses) and 4 different sensitivity analysis case definitions. RESULTS: The mean annual incidence of clinically diagnosed PsA among adults in Sweden in 2014-2016 was estimated at 21.77 per 100,000 person-years (PYs) at risk, according to the BC definition; 17.41 per 100,000 PYs at risk after accounting for diagnostic misclassification; and 15.78 to 28.83 per 100,000 PYs at risk across all sensitivity analyses. Incidence was slightly higher in female individuals, was lower in those with higher education (aged > 12 years), and peaked during the ages of 50 to 59 years. No apparent increasing or decreasing time trend was observed in 2006-2018. Within 2 years of diagnosis, 71.03% of patients had received DMARD therapy (22.37% biologic or targeted synthetic DMARDs). CONCLUSION: From 2014 to 2016, the annual incidence of clinically diagnosed PsA in the adult Swedish population was approximately 20 per 100,000 PYs at risk. Two years after diagnosis, almost three-quarters of patients had received DMARD therapy.

Giant cells in temporal artery biopsies and the risk of large vessel involvement in patients with giant cell arteritis.

OBJECTIVES: Giant cell arteritis (GCA) is a systemic disease with variable vascular involvement. The objective was to investigate predictors of time-dependent large vessel involvement (LVI) in a population-based cohort of patients with GCA. METHODS: GCA patients with positive temporal artery biopsies (TAB) between 1997- 2010 were identified through a regional pathology register. A structured review of histopathology reports and relevant imaging studies was performed. Cases with LVI through July 2016 were identified. Patients were followed to first LVI, death, migration from the area or July 29, 2016. Event free survival by clinical and histopathologic features was estimated using the Kaplan-Meier method. Potential predictors of LVI were examined using Cox regression models. RESULTS: A total of 274 patients were included. The mean age at GCA diagnosis was 75.7 years. Fifty-one patients (19 %) had documented LVI during the follow-up, corresponding to an incidence rate of 2.4/100 person-years. The median time from GCA diagnosis to the diagnosis of LVI was 4.5 years (interquartile range 0.6-7.4). Thirty-four patients had aortic involvement (67% of those with LVI; 12% of all GCA cases). Survival free of LVI was longer in patients with giant cells in the TAB (75th percentile 14.0 vs 6.7 years; p=0.014). In age-adjusted analysis, the presence of giant cells in the TAB was associated with reduced risk of LVI (hazard ratio 0.48; 95 % confidence interval 0.27-0.86). CONCLUSIONS: The negative association with giant cells in the TAB suggests that patients with LVI constitute a subset of GCA with particular disease mechanisms.

Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis: a prospective study.

OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of GCA. METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447), established 1991-96, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth and year of screening were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on eigenvalues, proteins with a factor loading of >0.50 were investigated. RESULTS: Ninety-four cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA [odds ratio (OR) per s.d. 1.52; 95% CI 1.00, 2.30]. Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14, 4.92) and monocyte chemotactic protein 3 (MCP3) (OR 4.27; 95% CI 1.26, 14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25. CONCLUSION: Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.

Genome-wide investigation of persistence to treatment with methotrexate in early rheumatoid arthritis.

OBJECTIVES: To investigate the influence of genetic factors on persistence to treatment of early rheumatoid arthritis (RA) with methotrexate (MTX) monotherapy. METHODS: We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early RA patients initiating MTX in DMARD-monotherapy as their first ever DMARD. The outcome, short- and long-term persistence to this treatment, was defined as remaining on MTX at one and at three years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus. RESULTS: No individual SNP reached genome-wide significance (p < 5e-8), neither for persistence at one nor at three years. The RA PRS was not significantly associated with persistence at one (RR = 0.98 (0.96-1.01)) nor three years (RR = 0.96 (0.93-1.00)). The heritability for persistence was estimated to be 0.45 (0.15-0.75) at one year and 0.14 (0-0.40) at three years. Results in seropositive RA were comparable to those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA. CONCLUSIONS: Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, persistence to MTX monotherapy was lower in patients with a greater genetic disposition, per the PRS, towards RA.

Lower Frequency of Comorbidities Prior to Onset of Giant Cell Arteritis: A Population-Based Study.

OBJECTIVE: To assess the frequency of comorbidities and metabolic risk factors at and prior to giant cell arteritis (GCA) diagnosis. METHODS: This is a retrospective case control study of patients with incident GCA between January 1, 2000, and December 31, 2019, in Olmsted County, Minnesota. Two age- and sex-matched controls were identified, and each assigned an index date corresponding to an incidence date of GCA. Medical records were manually abstracted for comorbidities and laboratory data at incidence date, 5 years, and 10 years prior to incidence date. Twenty-five chronic conditions using International Classification of Diseases, 9th revision, diagnosis codes were also studied at incidence date and 5 years prior to incidence date. RESULTS: One hundred and twenty-nine patients with GCA (74% female) and 253 controls were identified. At incidence date, the prevalence of diabetes mellitus (DM) was lower among patients with GCA (5% vs 17%; P = 0.001). At 5 years prior to incidence date, patients were less likely to have DM (2% vs 13%; P < 0.001) and hypertension (27% vs 45%; P = 0.002) and had a lower mean number (SD) of comorbidities (0.7 [1.0] vs 1.3 [1.4]; P < 0.001) compared to controls. Moreover, patients had significantly lower median fasting blood glucose (FBG; 96 mg/dL vs 104 mg/dL; P < 0.001) and BMI (25.8 vs 27.7; P = 0.02) compared to controls. Multivariable logistic regression analysis revealed negative associations for FBG with GCA at 5 and 10 years prior to diagnosis/index date. CONCLUSION: DM prevalence and median FBG and BMI were lower in patients with GCA up to 5 years prior to diagnosis, suggesting that metabolic factors influence the risk of GCA.

An update on polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2-3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL-6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15-25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC-related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease-modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment.

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.

Effectiveness of baricitinib and tofacitinib compared with bDMARDs in RA: results from a cohort study using nationwide Swedish register data.

OBJECTIVES: To describe the use of baricitinib and tofacitinib by Swedish RA patients and to compare their effectiveness with that of biologic DMARDs (bDMARDs). METHODS: RA patients who initiated baricitinib (n = 1420), tofacitinib (n = 316), abatacept (n = 1050), IL-6 inhibitors (IL-6is; n = 849), rituximab (n = 1101) or TNF inhibitors (TNFis; n = 6036) between January 2017 and November 2019 were followed for a minimum of 1 year using data from several linked Swedish national registers. Proportions reaching a good EULAR 28-joint DAS (DAS28) response, HAQ Disability Index (HAQ-DI) improvement >0.2 units and Clinical Disease Activity Index (CDAI) remission were compared at 1 year, imputing discontinued treatments as 'non-response'. Additionally, we compared drug retention and changes in DAS28, HAQ-DI and CDAI from baseline to 3 months after treatment initiation. RESULTS: On average, baricitinib, and particularly tofacitinib, were initiated as later lines of therapy and more frequently as monotherapy compared with rituximab and TNFi. Adjusted 1 year response proportions were consistently lower on TNFi compared with baricitinib, with differences of -4.3 percentage points (95% CI -8.7, 0.1) for good EULAR response, -9.9 (-14.4 to -5.4) for HAQ-DI improvement and -6.0 (-9.8 to -2.2) for CDAI remission. Comparisons with non-TNFi bDMARDs also favoured baricitinib, but not consistently. Treatment responses for tofacitinib were only marginally lower than those for baricitinib and generally similar to those of bDMARDs, with precision limited by low power. Comparisons of drug retention and changes in disease activity from baseline to 3 months supported the 1 year findings. CONCLUSIONS: Baricitinib and tofacitinib showed at least equivalent effectiveness compared with bDMARDs after exploring several different effectiveness measures.

Proteomic Data Analysis for Differential Profiling of the Autoimmune Diseases SLE, RA, SS, and ANCA-Associated Vasculitis.

Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), and healthy controls to identify candidate biomarker signatures for differential classification. A total of 316 serum samples collected from patients with SLE, RA, SS, or SV and from healthy controls were analyzed using 394-plex recombinant antibody microarrays. Differential protein expression profiling was examined using Wilcoxon signed rank test, and condensed biomarker panels were identified using advanced bioinformatics and state-of-the art classification algorithms to pinpoint signatures reflecting each disease (raw data set available at https://figshare.com/s/3bd3848a28ef6e7ae9a9.). In this study, we were able to classify the included individual IRDs with high accuracy, as demonstrated by the ROC area under the curve (ROC AUC) values ranging between 0.96 and 0.80. In addition, the groups of IRDs could be separated from healthy controls at an ROC AUC value of 0.94. Disease-specific candidate biomarker signatures and general autoimmune signature were identified, including several deregulated analytes. This study supports the rationale of using multiplexed affinity-based technologies to reflect the biological complexity of autoimmune diseases. A multiplexed approach for decoding multifactorial complex diseases, such as autoimmune diseases, will play a significant role for future diagnostic purposes, essential to prevent severe organ- and tissue-related damage.

Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population: a nationwide Swedish cohort study.

OBJECTIVES: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies. METHODS: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression. RESULTS: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited. CONCLUSIONS: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.

Evaluation of revised classification criteria for giant cell arteritis and its clinical phenotypes.

BACKGROUND: GCA is a systemic vasculitis of the elderly, viewed by many as a disease with multiple and overlapping clinical phenotypes. Retrospective studies have shown differences in clinical presentation between these phenotypes. To reflect the heterogeneity of GCA and novel diagnostic methods, new classification criteria have been proposed. METHODS: This is a retrospective study of newly diagnosed patients with GCA at the outpatient rheumatology clinics at Skåne University Hospital (Malmö and Lund) between 2012 and 2018. All patients were evaluated using two sets of classification criteria, the ACR classification criteria from 1990 and a proposed revision of these criteria requiring objective findings (positive biopsy or imaging) for classification. Patients were further classified as one of four widely used clinical phenotypes. RESULTS: A total of 183 patients with a new diagnosis of GCA were identified. The diagnosis was confirmed by one or two experienced rheumatologists in 116 of these patients during a review of medical records. The ACR criteria were more sensitive than the revised criteria (93.1% vs 72.4%), but the revised criteria had higher specificity (94.0% vs 28.4%). The revised criteria tended to have higher sensitivity in the phenotype with constitutional symptoms compared with cranial GCA (P = 0.08). CONCLUSION: The specificity of the ACR classification criteria for GCA can be improved by using revised criteria requiring objective findings of vasculitis. In addition, the wider symptoms covered by the revised criteria may improve classification of patients with a phenotype characterized by constitutional symptoms.

Epidemiology of biopsy-confirmed giant cell arteritis in southern Sweden-an update on incidence and first prevalence estimate.

OBJECTIVE: To characterize the epidemiology of temporal artery biopsy-positive (TAB+) GCA, including trends in incidence, seasonal variation and prevalence in Skåne, the southernmost region of Sweden. METHODS: All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date. RESULTS: One thousand three hundred and sixty patients were diagnosed with TAB+ GCA (71% female). The average annual incidence 1997-2019 was 13.3 (95% CI: 12.6, 14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95% CI: 16.7, 18.9) than in males (8.2; 95% CI: 7.4, 9.0). The age- and sex-standardized incidence declined from 17.3 in 1997 to 8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95% CI: 0.98, 0.99). A seasonal variation was observed with higher incidence during spring than winter [IR = 1.19 (95% CI: 1.03, 1.39)]. The overall point-prevalence of TAB+ GCA was 127.1/100 000 (95% CI: 117, 137.3) and was 75.5 (95% CI: 67.7, 83.3) when including only patients receiving immunosuppressants. CONCLUSION: Over the past 2 decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.

The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries.

OBJECTIVES: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. METHODS: We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. RESULTS: Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). CONCLUSION: Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.

2018 Update of the EULAR recommendations for the management of large vessel vasculitis.

BACKGROUND: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.