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.

Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis - relationship with the reason for withdrawal from the previous treatment.

OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.

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.

Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network.

OBJECTIVE: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. RESULTS: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). CONCLUSION: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.

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.

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.

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.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). METHODS: Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. RESULTS: Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. CONCLUSION: Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

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.

Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors: Data from the EuroSpA collaboration.

OBJECTIVES: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. METHODS: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. RESULTS: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97-0.98), men vs. women: 1.88 (1.60-2.22), current vs. non-smoking: 0.76 (0.63-0.91), HLA-B27 positive vs. negative: 1.51 (1.20-1.91), TNF start year 2015-2018 vs. 2009-2014: 1.24 (1.06-1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25-1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58-1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99-1.00) and 0.99 (0.99-1.99), respectively CONCLUSION: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.

Diagnosis, management, and outcome of cardiac sarcoidosis and giant cell myocarditis: a Swedish single center experience.

BACKGROUND: Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM. METHOD: We compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020. RESULTS: The median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5-60.9] and 2.98 [0.6-40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001). CONCLUSION: GCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.

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.

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.

One-Year Treatment Outcomes of Secukinumab Versus Tumor Necrosis Factor Inhibitors in Spondyloarthritis: Results From Five Nordic Biologic Registries Including More Than 10,000 Treatment Courses.

OBJECTIVE: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. METHODS: This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj ] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score <2.1, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] <40 mm, crude/LUNDEX-adjusted, adjusted logistic regression analyses with odds ratios [ORs]) stratified by line of biologic treatment (first, second, and third plus). RESULTS: In total, 10,853 treatment courses (842 secukinumab and 10,011 TNFi, of which 1,977 were adalimumab) were included. The proportions of patients treated with secukinumab during the first, second, and third-plus lines of treatment were 1%, 6%, and 22%, respectively). Extraarticular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a 1-year retention comparable to adalimumab as a first or second line of treatment but poorer as a third-plus line of therapy (secukinumab 56% [95% confidence interval (95% CI) 51-61%] versus adalimumab 70% [95% CI 64-75%]; HRadj 1.43 [95% CI 1.12-1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score <2.1 OR 0.56 [95% CI 0.35-0.90]; BASDAI <40 mm OR 0.62 [95% CI 0.41-0.95]). Treatment outcomes varied across the 5 TNFi. CONCLUSION: Secukinumab was mainly used in biologics-experienced patients with SpA. Secukinumab and adalimumab performed similarly in patients who had failed a first biologic, although with increasing prior biologic exposure, adalimumab was superior.

Lifestyle Factors and Disease Activity Over Time in Early Axial Spondyloarthritis: The SPondyloArthritis Caught Early (SPACE) Cohort.

OBJECTIVE: Our aim was to study the importance of baseline BMI, smoking, and alcohol consumption (AC) for disease activity (DA) over 1 year in early axial spondyloarthritis (axSpA), stratified by sex. METHODS: In the SPondyloArthritis Caught Early cohort (patients with chronic back pain onset at age < 45 yrs, with pain for ≥ 3 months and ≤ 2 yrs), the Ankylosing Spondylitis Disease Activity Score (ASDAS) was recorded at inclusion, 3, and 12 months. All patients included in the analysis had axSpA based on a high physician's level of confidence at baseline. Differences in ASDAS over 1 year by BMI (normal < 25 kg/m2, overweight 25-29.9 kg/m2, and obese ≥ 30 kg/m2), smoking history (never/previous/current), and AC (none, 0.1-2 units/week, 3-5 units/week, and ≥ 6 units/week) at baseline were estimated using mixed linear regression models. RESULTS: There were 344 subjects (mean age of 30.3 yrs; 49.4% men). In women, obesity was associated with 0.60 (95% CI 0.28-0.91) higher ASDAS compared to normal BMI. In both sexes, AC tended to be associated with lower DA over 1 year, with a significant association only in women with the highest AC (mean difference of -0.55, 95% CI -1.05 to -0.04). Smoking was associated with higher ASDAS over 1 year compared to never smoking in both sexes, although the difference reached statistical significance only in female former smokers. Results were similar in multivariable analysis, adjusted for all lifestyle factors and other confounders. CONCLUSION: In early axSpA, BMI and smoking are associated with higher DA over 1 year, and AC with lower DA. The magnitude of the modest associations may differ between men and women.

Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter?

BACKGROUND: The effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi). METHODS: Patients with SpA starting secukinumab or a TNFi 2015 through 2018 were identified in the Swedish Rheumatology Quality Register. Occurrence of AU was identified based on diagnosis codes in outpatient ophthalmology care in the National Patient Register. The main outcomes were crude rates of AU-diagnoses per 100 patient-years, and adjusted HRs for AU, during treatment, in patients without AU during the year before treatment start (in order to reduce confounding by indication). HRs were adjusted for age, sex, history of AU and patient global assessment of disease activity. RESULTS: Based on 4851 treatment starts (456 secukinumab; 4395 any TNFi), the rate of AU-diagnoses per 100 patient-years was 6.8 (95% CI 5.2 to 8.7) for secukinumab. Among the TNFi, the rate varied from 2.9 (95% CI 2.1 to 3.7) for infliximab and 4.0 (95% CI 3.3 to 4.9) for adalimumab to 7.5 (95% CI 6.7 to 8.4) for etanercept. The adjusted HRs for first AU (adalimumab as reference) were: secukinumab 2.32 (95% CI 1.16 to 4.63), infliximab 0.99 (95% CI 0.49 to 1.96), etanercept 1.82 (95% CI 1.13 to 2.93), golimumab 1.59 (95% CI 0.90 to 2.80) and certolizumab 1.12 (95% CI 0.44 to 2.83). Sensitivity analyses confirmed the pattern of higher AU rates with secukinumab and etanercept versus monoclonal TNFi. CONCLUSION: As used in clinical practice in SpA, secukinumab appears to be associated with a higher risk of AU, compared with the monoclonal TNFi and a similar risk compared with etanercept.

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.

BACKGROUND: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. METHODS: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. RESULTS: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. CONCLUSION: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.