Daniela Di Giuseppe

Objectives: This study aimed to, in patients with rheumatoid arthritis (RA), describe patterns and changes in healthy lifestyle habits (HLHs: alcohol use, smoking and physical activity) from diagnosis of RA to three years post-diagnosis, and to identify factors associated with having multiple HLHs. Methods: Patients’ data were collected from the Swedish Epidemiological Investigation of RA (EIRA). Physical activity (PA) was categorized to be on a healthy level if >120 min/week at moderate intensity. Smoking was categorized as smoking/non-smoking. Alcohol consumption of <120 g/week was deemed healthy. Participants were grouped by number of HLHs: none, one, two or three. Factors associated with having three HLHs at year three were analysed using logistic factor regression. Results: Among 1097 participants, 56% had three HLHs at baseline, increasing slightly to 58% at year three. Non-smoking increased from 77% to 83%, and healthy alcohol use from 85% to 97%. However, the proportion of participants who achieved a healthy level PA decreased from 84% to 71%. Having three HLHs at year three was associated with younger age [OR = 2.45 (95% CI = 1.50–4.00) for <35 vs 55–65 years] and living with another adult age [OR = 1.68 (95% CI = 1.25–2.26)]. Conclusion: More than half of the participants had three HLHs at diagnosis and maintained them after three years. Smoking and alcohol habits improved, but the proportion of participants who achieved a healthy level PA decreased. Older patients may need more support in adopting and maintaining HLHs.

Objectives: To investigate associations between cardiometabolic comorbidities and clinical characteristics, prescription patterns and retention of first biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) in patients with psoriatic arthritis (PsA). Methods: Patients with PsA initiating a first b/tsDMARD treatment in 2015 or later were identified in eight European rheumatology registries. Patients with information on five cardiometabolic comorbidities (obesity, dyslipidaemia, diabetes, hypertension, ischaemic heart disease) at treatment start (baseline) were included. All analyses were conducted according to patients’ comorbidity burden (count: 0/1/≥2) and status (presence/absence of each comorbidity). Patient characteristics and prescription patterns were described. Twelve-month treatment retention rates were estimated and compared using Kaplan-Meier plots, log-rank tests and multivariable Cox regression analyses. Results: Among 5299 patients, 36% had at least one cardiometabolic comorbidity. Patients with comorbidity were older, had higher disease activity and more disability. Regardless of comorbidity, most patients were prescribed a tumour necrosis factor inhibitor (76%). The use of interleukin-17 inhibitors increased with comorbidity burden (0/1/≥2 comorbidities: 13%/18%/19%), whereas Janus kinase inhibitor use declined (2.3%/1.6%/0.8%). Retention rates were marginally lower with higher comorbidity burden (80%/76%/78%) (log-rank, p=0.036) and obesity (absent 79% vs present 77%) (log-rank, p=0.04). The risk of treatment withdrawal was only marginally higher in patients with higher comorbidity burden (one comorbidity: HR 1.19; 95% CI 1.02 to 1.40; ≥2 comorbidities: HR 1.18; 0.98 to 1.42). Conclusion: Patients with cardiometabolic comorbidities had higher disease activity at treatment initiation of the first b/tsDMARD. Prescription patterns varied with comorbidity burden. Cardiometabolic comorbidity burden, especially obesity, was associated with marginally lower treatment retention.

Objectives: Rheumatoid arthritis (RA) is a disease with a heterogeneous phenotype. Partly, this heterogeneity may be concealed by metrics such as 28-joint disease activity score (DAS28) that may assign similar scores to dissimilar phenotypes. To explore how individual patient profiles may be separated, we developed three classification schemes and compared these with DAS28 in newly diagnosed RA. Methods: We selected patients aged 18–100 years, newly diagnosed with RA between 2012 and 2022 and registered in the Swedish Rheumatology Quality Register. We devised three alternative classifications based on (i) a subjective-objective decomposition of the DAS28 (seven levels), (ii) clinical experience-based cut-offs for each of the DAS28 components (five levels) and (iii) a data-driven Gaussian Mixture Model (five clusters). For each classification, we calculated descriptive statistics for clinical characteristics, demographic variables and comorbidity histories, and contrasted these with those based on DAS28 categories in our study population. Results: We identified 6624 patients with complete data on all included variables. In each of the alternative classifications, subjectively dominated and objectively dominated subsets captured differences regarding comorbidity histories not detectable in the DAS28 categories. Across all alternative classifications, subjectively dominated subsets had lower work ability than objectively dominated subsets and included 50%–300% more patients with pain and psychiatric diagnoses prior to RA diagnosis. Conclusions: Separating subjective and objective dimensions reveals different RA patient profiles that are grouped together by DAS28, demonstrating the extent to which DAS28 is confounded by factors beyond RA disease activity. Disentangling and treating heterogeneous RA patient profiles may therefore require more granular disease activity classification systems.

Objective: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is widely used for assessing disease activity in patients with axial spondyloarthritis (axSpA), particularly in settings where markers of inflammation are unavailable. As no consensus on BASDAI cut‐off values exists for disease activity states in axSpA, we aimed to develop and validate such cut‐offs against external criteria. Methods: Routine care patients with axSpA initiating a biologic disease‐modifying antirheumatic drug in eight European registries were included. Receiver operating characteristic analyses against external criteria were performed to determine optimal BASDAI values for separating remission, low disease activity (LDA), high disease activity (HDA), and very high disease activity (VHDA). Follow‐up data at 6 months were used to select BASDAI cut‐off values between remission and LDA and between LDA and HDA, whereas baseline data were used to select the cut‐off for VHDA. The level of agreement between disease activity states based on BASDAI and Axial Spondyloarthritis Disease Activity Score (ASDAS) cut‐off values was assessed using the proportion of discordance and weighted kappa. Results: In this cohort of 4,633 patients, the optimal BASDAI cut‐off values between remission, LDA, HDA and VHDA were estimated to be 4,600 patients. These cut‐off values can be used for assessing disease activity and monitoring patients with axSpA, particularly when laboratory markers are unavailable.

Objectives: Multiple discontinuations of biologic (b-) or targeted synthetic (ts-) disease-modifying antirheumatic drugs (DMARDs) may indicate difficult-to-treat disease. We aimed to assess the occurrence of b/tsDMARD discontinuations in patients with rheumatoid arthritis (RA), specifically how this varies by definition, across patient subsets and over time. Methods: Observational cohort study using data from the Swedish Rheumatology Quality Register on patients diagnosed with RA between 2010 and 2019. We identified three populations: (1) newly diagnosed (N=17 780), (2) initiating a first-ever DMARD (N=18 038) and (3) initiating a first-ever b/tsDMARD (N=8075). In each, we assessed the proportions and characteristics of patients fulfilling either of seven alternative DMARD discontinuation criteria (each encompassing a unique combination of number and type(s) of b/tsDMARD). Results: At 4.5 years of follow-up, 10% in populations (1) and (2), and 25% in (3), had discontinued ≥2 b/tsDMARDs with different modes of action. The proportions meeting each of the other six definitions ranged from 0.3% to 10% in (1) and (2), and 1% to 25% in (3). Regardless of definition or time, the characteristics of discontinuers across populations (1) through (3) remained largely similar. Conclusions: Applying treatment discontinuation-based definitions to an unselected RA population identifies widely varying proportions of patients with largely similar characteristics. Quantitatively, treatment-based definitions, follow-up time and study population must be clearly specified; qualitatively, the specific definition may be less critical.

To investigate a patient-level single imputation approach for patient reported outcomes (PROs) that express similar contents or associated PROs, where a PRO whose value is missing at a particular timepoint is substituted by another PRO whose value is available at the same timepoint. We performed a simulation study on registry-based spondyloarthritis data to explore the potential interchangeability between the patient pain (PPA) and fatigue (PFA) assessment scores and relevant Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) individual questions, and between PPA, PFA and patient global assessment (PGA). Performance was assessed per imputation method in terms of relative bias and coverage. Sample size, level of missingness and missing data pattern were included as parameters in the simulations. All applied scenarios to interchange PPA with BASDAI question 2 (axial pain), BASDAI question 3 (peripheral joint pain/swelling) or their average failed. Interchangeability between PFA and BASDAI question 1 (fatigue/tiredness) was acceptable for partially (up to 50%) missing data. When interchanging patient assessment scores (PPA, PFA and PGA), we observed inconsistent results in terms of performance. The performance of the applied methods depended on the sample size and the level of missingness, but not heavily on the underlying missing data pattern. Interchanging PFA and the BASDAI fatigue question was justified for partially missing data, while interchangeability between PPA, PFA and PGA, and between PPA and the BASDAI pain questions was not advised. Our findings suggest that registering patient assessment scores and BASDAI questions is recommended.

Aims/hypothesis: Some studies find an increased risk of type 1 diabetes in children exposed to antibiotics. We investigated if exposure to antibiotics increases the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Methods: We used data from a Swedish case–control study (Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes [ESTRID]: LADA, n=597; type 2 diabetes, n=2065; control participants matched on participation time, n=2386) and a case–control study nested within the Norwegian Trøndelag Health Study (HUNT) (n=82/1279/2050). Anatomical Therapeutic Chemical (ATC) codes indicating antibiotic dispensations were retrieved from the Swedish National Prescribed Drug Register and Norwegian Prescription Database. Multivariable adjusted ORs with 95% CIs were estimated by conditional logistic regression and pooled using fixed-effects inverse-variance weighting. Results: We observed no increased risk of LADA with exposure to antibiotics up to 1 year (OR_pooled 1.15, 95% CI 0.93, 1.41) or 1–5 years (OR_pooled 0.98, 95% CI 0.80, 1.20) prior to diagnosis/matching for one or more vs no dispensation of any type of antibiotic. An increased risk was observed for one or more vs no dispensations of narrow-spectrum antibiotics, but not broad-spectrum antibiotics, 6–10 years prior to LADA diagnosis (OR_pooled 1.39, 95% CI 1.01, 1.91), which was driven by the Swedish data. There was little evidence of an increased risk of type 2 diabetes associated with antibiotic exposure 1–10 years prior to diagnosis. Conclusions/interpretation: We found no evidence that exposure to broad-spectrum antibiotics up to 10 years prior to diagnosis increases the risk of LADA. There was some indication of increased LADA risk with exposure to narrow-spectrum antibiotics, which warrants further investigation. Graphical