ASDAS-CRP and ASDAS-ESR cut-offs for disease activity states in axial spondyloarthritis - Are they interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) is recommended over erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1 and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from axSpA patients initiating a tumour necrosis factor inhibitor from nine European registries. ASDAS-ESR cut-offs were estimated using the Youden index. Level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3,664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9 and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries.

OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

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.

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.

Are JAKis more effective among elderly patients with RA, smokers and those with higher cardiovascular risk? A comparative effectiveness study of b/tsDMARDs in Sweden.

OBJECTIVES: To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking. METHODS: Through Swedish registers, we identified 13 493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age. RESULTS: Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%). CONCLUSIONS: As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.

Comparative cardiovascular safety with janus kinase inhibitors and biological disease-modifying antirheumatic drugs as used in clinical practice: an observational cohort study from Sweden in patients with rheumatoid arthritis.

OBJECTIVES: To compare the incidence of cardiovascular (CV) events in rheumatoid arthritis (RA) treated with janus kinase inhibitors (JAKi), tumour necrosis factor inhibitors (TNFi), or other biological disease-modifying antirheumatic drugs (bDMARDs), in clinical practice, and to contextualise these findings by comparing to the Swedish RA population and general population at large. METHODS: Patients with RA initiating JAKi, TNFi and non-TNFi bDMARDs were identified in the Swedish Rheumatology Quality Register between 2016 and 2021. Through linkages to national registers, a cohort of patients with RA, general population comparators, as well as covariates and incident major acute CV event (MACE, including myocardial infarction, stroke and fatal CV events) were identified until 2022. Crude and age-sex standardised rates were calculated and HRs estimated from multivariable Cox regression models using TNFi as reference. RESULTS: We identified 13 492 patients with RA initiating a JAKi, non-TNFi bDMARD or TNFi treatment. Among 3037 JAKi-initiators, 59 MACE events were observed. The age-sex standardised rates for MACE were similar in the JAKi (0.88 per 100 person years) and TNFi (0.91) cohorts. Fully adjusted models showed no increased rate of MACE with JAKi (HR=0.71, 95% CI 0.51 to 0.99), or non-TNFi bDMARD (HR=0.98; 95% CI 0.78 to 1.23) in comparison to TNFi. We found no evidence that this HR changed over time since treatment initiation. In a CV-enriched subset, we observed higher rates but similar HRs. CONCLUSIONS: As used in present clinical practice in Sweden, we found no evidence that CV risk is higher with JAKis than TNFis in RA.

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.

Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching.

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE.

Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe.

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations.

Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study.

INTRODUCTION: We aimed to compare the proportions of patients with newly diagnosed psoriatic arthritis (PsA) and rheumatoid arthritis (RA) remaining on methotrexate (regardless of other disease-modifying antirheumatic drug (DMARD)-changes), and proportions not having started another DMARD (regardless of methotrexate discontinuation), within 2 years of starting methotrexate, as well as methotrexate effectiveness. METHODS: Patients with DMARD-naïve, newly diagnosed PsA, starting methotrexate 2011-2019, were identified from high-quality national Swedish registers and matched 1:1 to comparable patients with RA. Proportions remaining on methotrexate and not starting another DMARD were calculated. For patients with disease activity data at baseline and 6 months, response to methotrexate monotherapy was compared through logistic regression, applying non-responder imputation. RESULTS: In total, 3642/3642 patients with PsA/RA were included. Baseline patient-reported pain and global health were similar, whereas patients with RA had higher 28-joint scores and evaluator-assessed disease activity. Two years after methotrexate start, 71% of PsA vs 76% of patients with RA remained on methotrexate, 66% vs 60% had not started any other DMARD, and 77% vs 74% had not started specifically a biological or targeted synthetic DMARD. At 6 months, the proportions of patients with PsA versus RA achieving pain-scores ≤15 mm were 26% vs 36%; global health ≤20 mm: 32% vs 42%; evaluator-assessed 'remission': 20% vs 27%, with corresponding adjusted ORs (PsA vs RA) of 0.63 (95% CI 0.47 to 0.85); 0.57 (95% CI 0.42 to 0.76) and 0.54 (95% CI 0.39 to 0.75). DISCUSSION: In Swedish clinical practice, methotrexate use is similar in PsA and RA, both regarding initiation of other DMARDs and methotrexate retention. On a group level, disease activity improved during methotrexate monotherapy in both diseases, although more so in RA.

The National Prevalence of Clinically Diagnosed Psoriatic Arthritis in Sweden in 2017.

OBJECTIVE: Psoriatic arthritis (PsA) prevalence estimates vary across studies; studies based on national data are few. We aimed to estimate the prevalence of clinically diagnosed PsA in Sweden in 2017, overall and stratified by sex, age, education, and geography, and to quantify disease-modifying antirheumatic drug (DMARD) use among those in contact with specialized rheumatology care between 2015 and 2017. METHODS: Individuals who were 18 to 79 years of age, alive and residing in Sweden on December 31, 2017, and had a prior PsA diagnosis were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). PsA prevalence was estimated according to a base case (BC) definition (ie, ≥ 1 main PsA International Classification of Diseases code from rheumatology or internal medicine departments in the NPR or a PsA diagnosis in the SRQ), according to 4 sensitivity analysis definitions, and for those seen in specialized rheumatology care between 2015 and 2017. In the latter group, DMARD use during 2017 was also assessed. Data for stratifications were retrieved from national registers. RESULTS: The crude national prevalence of PsA for adults, aged 18 to 79 years, was estimated at 0.39%, according to the BC definition; 0.34% after accounting for diagnostic misclassification; and 0.32% to 0.50% across all sensitivity analyses. The prevalence was lower in males and in those with a higher level of education. The prevalence for those seen in specialized rheumatology care between 2015 and 2017 was estimated at 0.24%. During 2017, 32% of patients in this population received biologic or targeted synthetic DMARDs, and 41% received conventional synthetic DMARDs only. CONCLUSION: The prevalence of clinically diagnosed PsA in adults, aged 18 to 79 years, in Sweden in 2017 was around 0.35%. Among PsA cases in recent contact with specialized rheumatology care, almost three-fourths received DMARD therapy in 2017.

Uptake and effectiveness of newer biologic and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis: results from five Nordic biologics registries.

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

Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme.

OBJECTIVE: Longitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi). METHODS: Nationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity. RESULTS: There were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib. CONCLUSION: Data from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks.

Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries.

OBJECTIVES: The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). METHODS: Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. RESULTS: Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaïve) and 1948 with secukinumab (11% bionaïve). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39-0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. CONCLUSION: When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.

Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: a Swedish comparative safety study among patients with rheumatoid arthritis.

OBJECTIVE: To assess and compare the incidence of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitors (TNFi) or other biological disease modifying antirheumatic drugs (bDMARDs). For contextualisation, to assess VTE incidences in the Swedish general population and in the RA source population. METHODS: We performed a nationwide register-based, active comparator, new user design cohort study in Sweden from 2010 to 2021. The Swedish Rheumatology Quality Register was linked to national health registers to identify treatment cohorts (exposure) of initiators of a JAKi, a TNFi, or a non-TNFi bDMARD (n=32 737 treatment initiations). We also identified a general population cohort (matched 1:5, n=92 108), and an 'overall RA' comparator cohort (n=85 722). Outcome was time to first VTE during the follow-up, overall and by deep vein thrombosis (DVT) and pulmonary embolism (PE). We calculated incidence rates (IR) and multivariable-adjusted HRs using Cox regression. RESULTS: Based on 559 incident VTE events, the age- and sex-standardised (to TNFi) IR (95% CI) for VTE was 5.15 per 1000 person-years (4.58 to 5.78) for patients treated with TNFi, 11.33 (8.54 to 15.04) for patients treated with JAKi, 5.86 (5.69 to 6.04) in the overall RA cohort and 3.28 (3.14 to 3.43) in the general population. The fully adjusted HR (95% CI) for VTE with JAKi versus TNFi was 1.73 (1.24 to 2.42), the corresponding HR for PE was 3.21 (2.11 to 4.88) and 0.83 (0.47 to 1.45) for DVT. CONCLUSIONS: Patients with RA treated with JAKi in clinical practice are at increased risk of VTE compared with those treated with bDMARDs, an increase numerically confined to PE.

Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking.

OBJECTIVE: Lung cancer is a common malignancy in rheumatoid arthritis (RA). Since smoking is a risk factor for both (seropositive) RA and lung cancer, it remains unclear whether RA, in itself, increases lung cancer risk. METHODS: We performed a population-based cohort study of patients with RA and individually matched general population reference individuals identified in Swedish registers and from the Epidemiological Investigation of RA early RA study, prospectively followed for lung cancer occurrence 1995-2018. We calculated incidence rates and performed Cox regression to estimate HRs including 95% CIs of lung cancer, taking smoking and RA serostatus into account. RESULTS: Overall, we included 44 101 patients with RA (590 incident lung cancers, 56 per 100 000), and 216 495 matched general population individuals (1691 incident lung cancers, 33 per 100 000), corresponding to a crude HR (95% CI) of 1.76 (1.60 to 1.93). In subset analyses, this increased risk remained after adjustment for smoking (HR 1.77, 95% CI 1.06 to 2.97). Compared with general population subjects who were never smokers, patients with RA who were ever smokers had almost seven times higher risk of lung cancer. In RA, seropositivity was a significant lung cancer risk factor, even when adjusted for smoking, increasing the incidence 2-6 times. At 20 years, the risk in patients with RA was almost 3%, overall and over 4% for patients who were ever smokers and had at least one RA autoantibody. CONCLUSIONS: Seropositive RA is a risk factor for lung cancer over and above what can be explained by smoking, although residual confounding by smoking or other airway exposures cannot be formally excluded. There is a need for increased awareness and potentially for regular lung cancer screening, at least in a subset of patients with RA.

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.

Investigation of the association between coffee and risk of RA-results from the Swedish EIRA study.

BACKGROUND: Studies on the association between coffee, a modifiable lifestyle factor, and rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, have been conflicting. The aim of the present study was to study the association between coffee consumption and risk of RA in the context of different lifestyle factors. METHODS: We included 2184 cases (72% women, mean age 55 years) newly diagnosed with RA during 2005-2018 in Sweden and 4201 controls matched on age, sex, and residential area. Data on coffee consumption was collected through a food frequency questionnaire and categorized into < 2 (reference), 2-< 4, 4-< 6, and ≥ 6 cups/day. We calculated odds ratios (OR) with 95% confidence intervals (CI) for coffee consumption and risk of RA, in a crude model (taking matching factors into account), and then adjusted first for smoking and further for BMI, educational level, alcohol consumption, and physical activity. We also stratified analyses on sex, smoking, rheumatoid factor, and anti-CCP2 status. RESULTS: In the crude model, high coffee consumption was associated with increased risk of RA (OR = 1.50, 95% CI 1.20-1.88 for ≥ 6 cups/day compared to < 2 cups). After adjusting for smoking, the OR decreased and was no longer statistically significant (OR = 1.16, 95% CI 0.92-1.46) and decreased further in the full model (OR = 1.14 95% CI 0.89-1.45). This pattern held true in all strata. CONCLUSION: The findings from this large, population-based case-control study did not support a significant association between coffee consumption and risk of RA as a whole nor within different subgroups.

The impact of a csDMARD in combination with a TNF inhibitor on drug retention and clinical remission in axial spondyloarthritis.

OBJECTIVES: Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. METHODS: Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start). RESULTS: Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis. CONCLUSION: This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.