Concomitant Sjögren's disease as a biomarker for treatment effectiveness in rheumatoid arthritis - results from the Swiss clinical quality management cohort.

OBJECTIVE: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren's disease (SjD). METHODS: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders. RESULTS: We identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07-1.6]; OMA HR 1.12 [0.91-1.37]; JAKi HR 0.97 [0.62-1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46-0.84]) and JAKi (HR 0.52 [0.28-0.96]). CONCLUSION: RA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi.

Impact of sex on spinal radiographic progression in axial spondyloarthritis: a longitudinal Swiss cohort analysis over a period of 10 years.

OBJECTIVE: To investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA). METHODS: AxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Progression was defined as an increase of ≥2 mSASSS units in 2 years. The relationship between sex and progression was investigated with binomial generalised estimating equation models, considering baseline spinal damage as an intermediate covariate. Additional analyses included adjustments for explanatory variables and multiple imputations for missingness. RESULTS: In a total of 505 axSpA patients (317 men and 188 women), mean±SD radiographic progression over 2 years was 1.0±2.8 years in men and 0.3±1.1 years in women (p<0.001). Male sex was associated with enhanced progression in a small model not including baseline damage (OR 3.41, 95% CI 1.87 to 6.21). Both a direct effect of male sex on spinal progression, and an indirect effect, via enhancement of baseline spinal damage were significant (OR 2.06, 95% CI 1.15 to 3.67 and OR 1.04, 95% CI 1.01 to 1.07, respectively). A significant impact of male sex on spinal radiographic progression was still demonstrated after multiple adjustments for covariates known to potentially affect spinal radiographic progression (OR 1.97, 95% CI 1.04 to 3.71). CONCLUSIONS: Spinal radiographic progression in axSpA is more severe in men than in women, with three times higher odds of progression in male patients and an effect that is mediated in part through an increase in baseline radiographic damage.

Obesity Represents a Persisting Health Issue in Axial Spondyloarthritis, Particularly Affecting Socially Disadvantaged Patients.

OBJECTIVE: Obesity is an important comorbidity in axial spondyloarthritis (axSpA); however, the prevalence of obesity in axSpA compared with the general population and associated socioeconomic factors remain unknown. METHODS: This repeated cross-sectional study compared BMI (kg/m2) groups of patients with axSpA to the Swiss population at 3 timepoints (2007, 2012, and 2017). BMI categories were compared by different age, sex, and education categories using the chi-square goodness of fit test. Unpaired, 1-sided t tests were used to compare the BMI in patients with axSpA between the different timepoints. RESULTS: Compared to the general population, patients with axSpA had a higher proportion of overweight and obesity: 18.9% of all patients with axSpA were obese, compared to 11.3% of the Swiss population in 2017. Comparison of BMI groups within sex, age, and education groups consistently showed a trend toward higher rates of overweight and obesity in axSpA. Further, patients with axSpA, especially females, showed a trend of increasing BMI over the studied 10 years. At every time point, overweight and obese patients were significantly more likely to be male, were older, and had higher disease activity than patients with normal weight. Obesity was associated with a deprived socioeconomic status as indicated by a higher proportion of patients with manual labor jobs and lower levels of education. CONCLUSION: The prevalence of obesity was significantly higher among patients with axSpA compared to the Swiss population, with socially disadvantaged individuals being the most affected. There is an urgent need to initiate prevention strategies for obesity in patients with axSpA.

Characterisation of patients with axial psoriatic arthritis and patients with axial spondyloarthritis and concomitant psoriasis in the SCQM registry.

BACKGROUND: Within the spectrum of spondyloarthritides, axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) present with overlapping features. Axial involvement in PsA (axial PsA) is treated according to recommendations for axSpA, as specific studies in axial PsA are scarce. We compared characteristics of patients with axSpA (particularly of patients with axSpA and concomitant psoriasis (pso)) with those of patients with axial PsA. METHODS: Patients with axSpA and PsA in the Swiss Clinical Quality Management (SCQM) registry were included if information on pso and axial involvement was available. Patients with AxSpA were stratified by axSpA with and without pso (axSpA±pso) and patients with PsA were stratified to axial PsA or strictly peripheral PsA. RESULTS: Previous or current psoriasis was observed in 479/4489 patients with axSpA (10.7%). Of 2631 patients with PsA, 1153 (43.8%) presented with axial involvement (opinion of the treating rheumatologist). Compared with patients with axSpA+pso, patients with axial PsA were older at symptom onset and at inclusion in SCQM, were less frequently HLA-B27 positive, had back pain less frequently and a higher prevalence of dactylitis and peripheral arthritis. A positive family history of pso or PsA was more frequent in axial PsA, while a positive family history of axSpA was more frequent in patients with axSpA+pso. Disease activity, function and mobility were comparable in axSpA+pso versus axial PsA. CONCLUSION: Patients with axial PsA differ from patients with axSpA+pso in important demographic and clinical characteristics, and genetically, but present with a comparable disease burden. Treatment studies specifically dedicated to axial PsA seem warranted.

Anaemia is associated with higher disease activity in axial spondyloarthritis but is not an independent predictor of spinal radiographic progression: data from the Swiss Clinical Quality Management Registry.

OBJECTIVE: As anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA). METHODS: AxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values. RESULTS: A total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years. CONCLUSION: Although anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression. Key Points • Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA. • Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression.

Site-specific assessment of spinal radiographic progression improves detection of TNF blocker-associated disease modification in axial spondyloarthritis: longitudinal observational data from the Swiss Clinical Quality Management Registry.

OBJECTIVES: To analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine). METHODS: Patients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years. RESULTS: Mean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14-0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52-1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24-0.77 and 0.85, 95% CI 0.51-1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12-0.80 versus OR 0.56, 95% CI 0.26-1.24 for the cervical and lumbar spine, respectively). CONCLUSION: Disease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

HLA-B27 as a predictor of effectiveness of treatment with TNF inhibitors in axial spondyloarthritis: data from the Swiss Clinical Quality Management Registry.

OBJECTIVE: To explore the impact of the human leucocyte antigen (HLA)-B27 on the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). METHODS: A total of 1109 patients with available HLA-B27 status (831 B27+ patients and 278 B27- patients) fulfilling the Assessment of Spondyloarthritis international Society classification criteria for axSpA from the prospective Swiss Clinical Quality Management Registry initiating a first TNFi were included. Drug retention was investigated with multiple adjusted Cox proportional hazard models with imputation of missing values. Multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year. RESULTS: B27+ and B27- patients differed with regard to age, sex, BASDAI, C-reactive protein (CRP), body mass index, enthesitis, uveitis, and classification status. After adjustment for potential confounders for the relationship between HLA-B27 and drug effectiveness (sex and family history of spondyloarthritis), a higher risk of drug discontinuation was found in B27- patients (HR 1.53, 95% CI 1.27-1.83). This difference decreased after additional adjustment for parameters which may act as mediators (HR 1.30, 95% CI 1.30-1.55). Male sex and elevated C-reactive protein (CRP) levels were consistently associated with longer retention. Comparable results were obtained for BASDAI50 responses. CONCLUSION: The HLA-B27 genotype is an important predictor of treatment effectiveness. Male sex and CRP seem, however, to better describe variability of response in individual patients. This data may help avoiding potential discrimination of B27- individuals with regard to TNFi initiation. Key Points • HLA-B27 is a predictor of effectiveness of TNF inhibitors in axial spondyloarthritis. • Variability of response in individual patients is better defined by sex and objective markers of disease activity, such as C-reactive protein.

Sacroiliac joint radiographic progression in axial spondyloarthritis is retarded by the therapeutic use of TNF inhibitors: 12-year data from the SCQM registry.

OBJECTIVES: To analyse the effect of tumour necrosis factor inhibitors (TNFi) on sacroiliac joint (SIJ) radiographic progression in axial spondyloarthritis (axSpA). METHODS: Patients with axSpA in the Swiss Clinical Quality Management cohort with up to 12 years of follow-up and radiographic assessments every 2 years were included. SIJs were scored by two readers according to the modified New York criteria blinded to chronology. The relationship between TNFi use before or during a 2-year radiographic interval and SIJ progression was investigated using generalised estimating equation models with adjustment for potential confounding. Progression was defined as worsening of ≥1 grade in ≥1 SIJ and ignoring a change from 0 to 1 over 2 years, if both readers agreed. A third reading of radiographs was integrated in sensitivity analyses. RESULTS: A total of 515 patients with axSpA contributed to data for 894 radiographic intervals (24 progression events). In patients with complete covariate data, prior use of TNFi reduced the odds of progression (OR 0.21, 95% CI 0.07 to 0.65). A comparable effect was found for use of TNFi for ≥1 year within a 2-year radiographic interval (OR 0.21, 95% CI 0.08 to 0.55). The inhibitory impact of TNFi was confirmed if progression was demonstrated in 2/3 readings: OR 0.50, 95% CI 0.28 to 0.89 and OR 0.46, 95% CI 0.27 to 0.78 for TNFi treatment before and for ≥1 year within the interval, respectively. CONCLUSION: TNFi are associated with deceleration of SIJ radiographic progression in patients with axSpA if treatment is continued for ≥1 year.

Current differentiation between radiographic and non-radiographic axial spondyloarthritis is of limited benefit for prediction of important clinical outcomes: data from a large, prospective, observational cohort.

OBJECTIVE: To compare disease characteristics and outcomes between patients with axial spondyloarthritis with non-radiographic disease (nr-axSpA), bilateral grade 2 sacroiliitis (r22axSpA) and unilateral/bilateral grade 3-4 sacroiliitis (r3+axSpA) according to the modified New York criteria. METHODS: We included patients with axial spondyloarthritis with available pelvic radiographs from the Swiss Clinical Quality Management Cohort. Retention of a first tumour necrosis factor inhibitor (TNFi) was investigated with multiple adjusted Cox proportional hazards models. The proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year was assessed with multiple adjusted logistic regression analyses. Spinal radiographic progression, defined as an increase in ≥2 mSASSS units in 2 years, was assessed in generalised estimating equation models. RESULTS: From 2080 patients, those with nr-axSpA (n=485) and r22axSpA (n=443) presented with lower C reactive protein levels and less severe clinical spinal involvement compared with patients with r3+axSpA (n=1152). While TNFi retention was similar in r22axSpA and nr-axSpA, the risk of discontinuation was significantly lower in r3+axSpA (HR 0.60, 95% CI 0.44 to 0.82 vs nr-axSpA). BASDAI50 responses at 1 year were comparable in r22axSpA and nr-axSpA, with a better response associated with r3+axSpA (OR 2.05, 95% CI 1.09 to 3.91 vs nr-axSpA). Spinal radiographic progression was similar in r22axSpA and nr-axSpA and significantly higher in r3 +axSpA. CONCLUSION: Patients with r22axSpA are comparable to nr-axSpA patients but differ from patients with more severe sacroiliac damage with regard to treatment effectiveness and spinal radiographic progression. Therefore, current differentiation between nr-axSpA and radiographic disease seems of limited use for outcome prediction.

Rates of Hepatocellular Carcinoma After Start of Treatment for Chronic Hepatitis C Remain High with Direct Acting Antivirals: Analysis from a Swiss Liver Transplant Center.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. PATIENTS AND METHODS: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. RESULTS: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. CONCLUSION: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.