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Purpose With increased concomitant chronic diseases in type 2 diabetes mellitus (T2DM), the use of multiple drugs increases as well as the risk of drug–drug interactions (DDI) and adverse drug reactions (ADR). Nevertheless, how medication patterns vary in T2DM patients across different sex and age groups is unclear. This study aims to identify and quantify common drug combinations in first-time metformin users with polypharmacy (≥5 co-medications). Methods New users of metformin were identified from the IQVIA Medical Research Data incorporating data from THIN, A Cegedim Database (2016–2019). A descriptive cohort study explored prescription patterns in patients with polypharmacy. The Apriori algorithm, used to find frequent item-sets in databases, was first-time applied to identify and quantify drug combinations of up to seven drugs to investigate potential harmful polypharmacy patterns. Results The cohort included 34 169 new-users of metformin, of which 20 854 (61.0%) received polypharmacy. Atorvastatin was the most frequently co-prescribed drug with metformin overall (38.7%), in women (34.3%) and men (42.6%). In the stratified analysis, a higher proportion of women received polypharmacy (65.6%) compared to men (57.4%). Moreover, the proportion of patients receiving polypharmacy increased with age (18–39 years = 30.4%, 40–59 years = 50.5%, 60–74 years = 70.9%, and ≥75 years = 84.3%). Conclusion This study is the first to identify and quantify commonly prescribed combinations of drugs compounds in patients with polypharmacy using the Apriori algorithm. The high polypharmacy prevalence at all strata indicates the need to optimize polypharmacy to minimize DDI and ADR., Pharmacoepidemiology and Drug Safety, 32 (3), ISSN:1053-8569, ISSN:1099-1557

BackgroundObesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). Among obese patients, abatacept was suggested as a preferable option to tumour necrosis factor alpha (TNF) inhibitors. Sex and gender differences in RA were described.ObjectivesTo assess the comparative effectiveness of etanercept, infliximab, and abatacept, compared to adalimumab, in patients with RA stratified by body mass index (BMI) and sex.MethodsObservational cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997-2019). RA patients were classified in BMI-based cohorts: obese, overweight, and normal weight. Each BMI cohort was studied overall and stratified by sex. The study outcome was remission within 12-months, defined as a disease activity score (DAS28) ResultsThe study included 443 obese, 829 overweight, and 1243 normal weight RA patients. Across the BMI cohorts, there were no significant differences in the odds of remission at ≤12-months for the study drugs compared to adalimumab. However, among females, an inverse effect for infliximab was found, whereby overweight patients had higher odds of remission, while obese patients had lower odds of remission, compared to the respective adalimumab users.ConclusionsDespite the previous hypothesis, treatment with abatacept showed similar odds of remission compared to adalimumab in all BMI cohorts. Conversely, compared to adalimumab, infliximab performed better in overweight female patients but worse in female patients with obesity. However, further validation is needed.

To assess the impact of elevated body mass index (BMI) in the achievement of minimal disease activity (MDA) and several definitions of remission in patients with psoriatic arthritis (PsA) in Switzerland. Secondarily, to assess the overlapping across the study outcomes.This observational cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included patients with PsA starting their first biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) from 1997 to 30 June 2018. Exposure was BMI category at b/tsDMARD start: overweight, obese, and normal weight (reference). Logistic regression was used to assess the achievement of MDA and remission at ≤12 months, as well as treatment persistence at 1 year, in overweight patients and patients with obesity compared with the normal weight group. Remission was defined by Disease Activity for Psoriatic Arthritis (DAPSA), clinical DAPSA (cDAPSA) and 28-joint Disease Activity Score (DAS28). Additionally, overlapping across study outcomes was investigated.The study included 306 (39.5%) normal weight patients, 285 (36.8%) overweight patients and 183 (23.6%) patients with obesity. Compared with the normal weight group, patients with obesity had lower odds of achieving MDA at ≤12 months (adjusted OR (ORadj) 0.45, 95% CI 0.24 to 0.82). This was consistent with the observed reduced odds of achieving DAPSA-remission (ORadj 0.42, 95% CI 0.21 to 0.85), cDAPSA-remission (ORadj 0.51, 95% CI 0.27 to 0.96) and DAS28-remission (ORadj 0.51, 95% CI 0.32 to 0.81) in patients with obesity versus normal weight patients. Among the 125 patients achieving MDA, the majority (81.8% normal weight, 80.0% overweight, 78.9% obese) achieved cDAPSA-remission. No differences were observed in the odds to achieving treatment persistence between the BMI strata.Obesity halved the likelihood of achieving MDA and remission in patients with PsA with b/tsDMARDs compared with those with normal weight, while it did not impact treatment persistence. High overlapping of patients achieving the outcomes MDA and cDAPSA-remission was observed across every BMI group.

We aimed to assess the association between bariatric surgery and incident Dupuytren's disease (DD) using propensity score-matched cohort studies among Swedish nationwide healthcare registries. Patients aged 30-79 years who underwent bariatric surgery 2006-2019 were matched on their propensity scores, up to two obese bariatric surgery-free (unexposed) patients. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CI) for the risk of DD overall, in subgroups of age, sex, bariatric surgery type and duration of follow-up. Among 34,959 bariatric surgery patients and 54,769 propensity score-matched obese patients, the risk of DD was increased in bariatric surgery patients compared with obese unexposed patients (HR 1.30, 95% CI 1.02-1.65), among women (HR 1.36; 1.00-1.84); those undergoing gastric bypass (HR 1.33; 1.04-1.71) and those with >5 years follow-up (HR 1.63; 1.14-2.34). Our results suggest that substantial weight loss is associated with an increased risk of DD in an obese population., Journal of Hand Surgery (European Volume), 47 (3), ISSN:1753-1934, ISSN:2043-6289

Obesity is considered a risk factor for cataracts. The association between weight loss and a cataract among patients with obesity has not been assessed to date.To assess the association between weight loss following bariatric surgery and cataracts.Nationwide Swedish healthcare registries between 2006 and 2019.We performed a population-based cohort study. Patients aged 40-79 years who underwent bariatric surgery were matched on their propensity score (PS) to up to 2 patients with obesity ("unexposed patients"). Cox proportional hazard regression analyses calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of developing cataracts following bariatric surgery, compared with unexposed patients. Subgroup analyses by age, sex, bariatric surgery type, and duration of follow-up were conducted.In total, 22,560 bariatric surgery patients were PS-matched to 35,523 unexposed patients. The risk of cataracts was decreased in bariatric surgery patients compared with unexposed patients (HR .71, 95% CI .66-.76). We observed the lowest risk of cataracts among bariatric surgery patients aged 40-49 years (HR .52, 95% CI .44-.75) but a null result for patients aged ≥60 years. Gastric bypass or duodenal switch were associated with decreased risks of cataracts, whereas sleeve gastrectomy yielded a null result. Subgroups of sex and duration of follow-up showed no evidence of effect modification (hazards were proportional throughout follow-up).Our results suggest that substantial weight loss following bariatric surgery is associated with a decreased risk of cataracts, especially if bariatric surgery was performed before age 60.

Objectives To assess completeness and validity of bariatric surgery codes in the UK Clinical Practice Research Datalink (CPRD) GOLD compared with Hospital Episodes Statistics (HES). Methods We conducted a validation study among patients in the UK-based CPRD GOLD with linkage to HES (1998 to 2017). Since the same surgery codes are used for bariatric and other gastrointestinal surgery we assessed code distribution patterns used in patients with bariatric versus other gastrointestinal surgery by presence of other conditions such as obesity and gastrointestinal cancer. We developed algorithms to identify bariatric surgery and calculated validity measures (i.e. positive/negative predictive value [PPV/NPV], sensitivity, and specificity) of each in CPRD GOLD compared with HES (gold standard). Results Among 7 357 007 available patients we identified 10 190 patients who had a total of 14 046 potential bariatric surgery codes in CPRD GOLD and/or HES. Surgery code patterns differed between bariatric surgery and assumed other gastrointestinal surgery. The sensitivity of CPRD GOLD bariatric surgery coding improved from an overall of 56% to 69-71% when applying stricter algorithms (i.e. in obese patients or obese, gastrointestinal disease/complication free patients) but PPVs remained at 53-55%. NPVs and specificities of CPRD GOLD bariatric surgery coding achieved ≥99.8% for all algorithms. Conclusion Our results suggest that using CPRD GOLD and HES data and a wide selection of surgery codes will result in the most complete and accurate capture of bariatric surgery events. Validity measures of CPRD GOLD bariatric surgery codes were identical in obese patients and more restrictive populations.

Objectives A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA. Methods Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1. Results Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings. Conclusions These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA., Arthritis Research & Therapy, 23 (1), ISSN:1465-9905, ISSN:1465-9913, ISSN:1478-6362, ISSN:1478-6354

Background Statins are effective lipid-lowering drugs for the prevention of cardiovascular disease, but muscular adverse events can limit their use. Hydrophilic statins (pravastatin, rosuvastatin) may cause less muscular events than lipophilic statins (e.g. simvastatin, atorvastatin) due to lower passive diffusion into muscle cells. Objective To compare the risk of muscular events between statins at comparable lipid-lowering doses and to evaluate if hydrophilic statins are associated with a lower muscular risk than lipophilic statins. Design/Setting Propensity score-matched cohort study using data from the United Kingdom-based Clinical Practice Research Datalink (CPRD) GOLD. Patients New statin users. Cohort 1: pravastatin 20-40 mg (hydrophilic) vs simvastatin 10-20 mg (lipophilic), cohort 2: rosuvastatin 5-40 mg (hydrophilic) vs atorvastatin 10-80 mg (lipophilic), and cohort 3: simvastatin 40-80 mg vs atorvastatin 10-20 mg. Main Measures The outcome was a first record of a muscular event (myopathy, myalgia, myositis, rhabdomyolysis) during a maximum follow-up of 1 year. Key Results The propensity score-matched cohorts consisted of 1) 9,703, 2) 7,032, and 3) 37,743 pairs of statin users. Comparing the risk of muscular events between low-intensity pravastatin vs low-intensity simvastatin yielded a HR of 0.86 (95% CI 0.64-1.16). In the comparison of moderate- to high-intensity rosuvastatin vs equivalent doses of atorvastatin, we observed a HR of 1.17 (95% CI 0.88-1.56). Moderate- to high-intensity simvastatin was associated with a HR of 1.33 (95% CI 1.16-1.53), when compared with atorvastatin at equivalent doses. Limitations We could not conduct other pairwise comparisons of statins due to small sample size. In the absence of a uniform definition on the comparability of statin doses, the applied dose ratios may not fully match with all literature sources. Conclusions Our results do not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins at comparable lipid-lowering doses.

Background Elective total knee replacement (TKR) is a safe and cost-effective surgical procedure for treating severe knee osteoarthritis (OA). Although complications following surgery are rare, prediction tools could help identify those patients who are at particularly high risk who could then be targeted with preventative interventions. We aimed to develop a simple model to help inform treatment choices. Methods We trained and externally validated adverse event prediction models for patients with TKR using electronic health records (EHR) and claims data from the US (OPTUM, CCAE, MDCR, and MDCD) and general practice data in the UK (IQVIA Medical Research Database ([IMRD], incorporating data from The Health Improvement Network [THIN], a Cegedim database). The target population consisted of patients undergoing a primary TKR, aged ≥40 years and registered in any of the contributing data sources for ≥1 year before surgery. LASSO logistic regression models were developed for four adverse outcomes: post-operative (90-day) mortality, venous thromboembolism (VTE), readmission, and long-term (5-year) revision surgery. A second model was developed with a reduced feature set to increase interpretability and usability. Findings A total of 508,082 patients were included, with sample size per data source ranging from 1,853 to 158,549 patients. Overall, 90-day mortality, VTE, and readmission prevalence occurred in a range of 0.20%-0.32%, 1.7%-3.0% and 2.2%-4.8%, respectively. Five-year revision surgery was observed in 1.5%-3.1% of patients. The full model predicting 90-day mortality yielded AUROC of 0.78 when trained in OPTUM and yielded an AUROC of 0.70 when externally validated on THIN. We then developed a 12 variable model which achieved internal AUROC of 0.77 and external AUROC of 0.71 in THIN. The discriminative performances of the models predicting 90-day VTE, readmission, and 5-year revision were consistently poor across the datasets (AUROC Interpretation We developed and externally validated a simple prediction model based on sex, age, and 10 comorbidities that can identify patients at high risk of short-term mortality following TKR. Our model had a greater discriminative ability than the Charlson Comorbidity Index in predicting 90-day mortality. The 12-feature mortality model is easily implemented and the performance suggests it could be used to inform evidence based shared decision-making prior to surgery and for appropriate precautions to be taken for those at high risk. The other outcomes examined had low performance. Funding This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The sponsor of the study did not have any involvement in the writing of the manuscript or the decision to submit it for publication. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013-13-012). TDS is funded by the Department of Health of the Generalitat de Catalunya under the Strategic Plan for Research and Innovation in Health (PERIS; SLT002/16/00308). The views expressed in this publication are those of the authors and not those of the NHS, the National Institute for Health Research or the Department of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Key Points Question Is it possible to predict adverse events following total knee replacement? Findings Mortality was the only adverse event studied that we were able to predict with adequate performance. We produced a 12 variable prediction model for 90-day post-operative mortality that achieved an AUROC of 0.77 on internal test validation (Optum) and 0.71 when externally validated in THIN. The model also showed adequate calibration. Meaning Patients can now be presented with an accurate risk assessment for short term mortality such that they are well-informed before the decision for surgery is taken. Importance Total Knee Replacement is generally a safe, effective procedure that is performed on thousands of patients each year. However, a small number of those patients will experience adverse events. Due to the surgery’s elective nature, a well calibrated, high performing risk model could pre-emptively inform the patient and clinician decision making process and help to guide preventative treatment.

Background There is uncertainty around whether to use unicompartmental knee replacement (UKR) or total knee replacement (TKR) for individuals with osteoarthritis confined to a single compartment of the knee. We aimed to emulate the design of the Total or Partial Knee Arthroplasty Trial (TOPKAT) using routinely collected data to assess whether the efficacy results reported in the trial translate into effectiveness in routine practice, and to assess comparative safety. Methods We did a population-based network study using data from four US and one UK health-care database, part of the Observational Health Data Sciences and Informatics network. The inclusion criteria were the same as those for TOPKAT; briefly, we identified patients aged at least 40 years with osteoarthritis who had undergone UKR or TKR and who had available data for at least one year prior to surgery. Patients were excluded if they had evidence of previous knee arthroplasty, knee fracture, knee surgery (except diagnostic), rheumatoid arthritis, infammatory arthropathies, or septic arthritis. Opioid use from 91–365 days after surgery, as a proxy for persistent pain, was assessed for all participants in all databases. Postoperative complications (ie, venous thromboembolism, infection, readmission, and mortality) were assessed over the 60 days after surgery and implant survival (as measured by revision procedures) was assessed over the 5 years after surgery. Outcomes were assessed in all databases, except for readmission, which was assessed in three of the databases, and mortality, which was assessed in two of the databases. Propensity score matched Cox proportional hazards models were fitted for each outcome. Calibrated hazard ratios (cHRs) were generated for each database to account for observed differences in control outcomes, and cHRs were then combined using meta-analysis. Findings 33 867 individuals who received UKR and 557 831 individuals who received TKR between Jan 1, 2005, and April 30, 2018, were eligible for matching. 32 379 with UKR and 250 377 with TKR were propensity score matched and informed the analyses. UKR was associated with a reduced risk of postoperative opioid use (cHR from meta-analysis 0·81, 95% CI 0·73–0·90) and a reduced risk of venous thromboembolism (0·62, 0·36–0·95), whereas no difference was seen for infection (0·85, 0·51–1·37) and readmission (0·79, 0·47–1·25). Evidence was insufficient to conclude whether there was a reduction in risk of mortality. UKR was also associated with an increased risk of revision (1·64, 1·40–1·94). Interpretation UKR was associated with a reduced risk of postoperative opioid use compared with TKR, which might indicate a reduced risk of persistent pain after surgery. UKR was associated with a lower risk of venous thromboembolism but an increased risk of revision compared with TKR. These findings can help to inform shared decision making for individuals eligible for knee replacement surgery.

Background:Higher prevalence of obesity has been observed in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) versus the general population, and abnormal body mass index has been associated with worse rheumatic markers.Objectives:To describe PsA and RA patients in Switzerland, stratified by body mass index (BMI) category.Methods:We performed a descriptive cohort study in PsA and RA patients registered in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) database. Two distinct cohorts were generated based on patient diagnosis (PsA or RA) and analysed separately but using similar approaches. In both cohorts, we included patients treated for the first time with biologics or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), and considered the treatment start as index date. Patients without baseline BMI were excluded. Patients were stratified by BMI category at the start of biologic/tsDMARD treatment, defined as underweight (BMI12months from treatment start, and illustrated the prescription patterns for first and second biologic/tsDMARD treatment, stratifying by BMI.Results:We identified 819 PsA [39.7% normal weight, 36.5% overweight, 23.8% obese] and 3217 RA patients [4.4% underweight, 46.8% normal weight, 31.8% overweight, 17.0% obese]. Figure 1 illustrates the prevalence of overweight and obesity in each cohort stratified by sex, compared to the national average. When comparing obese patients to those with normal weight, both PsA and RA obese patients had significantly higher C-reactive protein, worse disease activity score, lower quality of life (QoL) measures, and more frequent cardiovascular disease and diabetes. Among PsA patients, the overweight and obese had worse physician-assessed skin manifestation and patient-reported pain compared to the normal weight group. While in RA, the obese patients had higher erythrocyte sedimentation rate, smaller prevalence of seropositive patients, lower frequency of fractures/surgeries, and higher tender joint counts, but similar swollen joint counts, when compared to the normal weight group.Adalimumab and etanercept, were the most commonly prescribed drugs as first biologic/tsDMARD treatment in both PsA and RA cohorts and among every BMI category. Overall, 55% PsA and 56% RA patients had recorded treatment stop/switch. Among RA patients, significantly fewer obese patients reported treatment stop/switch at >12 months from treatment start, compared to the normal weight group. Adalimumab and etanercept were also the most commonly prescribed second biologic/tsDMARD treatment, but for the obese group among PsA patients (adalimumab, golimumab) and the obese group in the RA cohort (adalimumab, rituximab).Conclusion:In this national wide study, we observed that the prevalence of obesity in RA and PsA was higher than that of the general Swiss population. Obese PsA/RA patients starting first biologic/tsDMARD treatment presented worse disease activity and poorer QoL than normal weight patients. Results suggest to take BMI into consideration when treating PsA and RA patients.Acknowledgements:We would like to thank all patients and rheumatologists contributing to the SCQM registry, as well as the entire SCQM staff. A list of rheumatology offices and hospitals which contribute to the SCQM registry can be found at http://www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found at http://www.scqm.ch/sponsors.Disclosure of Interests:Enriqueta Vallejo-Yagüe: None declared, Theresa Burkard: None declared, Burkhard Moeller Speakers bureau: AbbVie, Bristol Myers, Eli Lilly, Janssen, Pfizer, Roche, Novartis, Merck, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Grant/research support from: Pfizer, BMS, Novartis, Andrea Michelle Burden: None declared

Background:Dupuytren disease (DD) is multifactorial, with several genetic and environmental risk factors contributing to disease susceptibility. High body mass index, however, was suggested to be protective of DD.1 The impact of weight loss among obese patients on DD has not been assessed to date.Objectives:To assess the association between bariatric surgery and DD in a secondary care setting.Methods:We performed a propensity score (PS)-matched cohort study using data from Swedish nationwide healthcare registries (patient registry [secondary care], causes of death registry, prescribed drug registry). Patients aged 30-79 years who underwent bariatric surgery between 2006 and 2019 were matched to up to 2 obese bariatric surgery-free patients (called unexposed patients) based on their PS. PS-matching was carried out in risk set sampling to reduce selection bias, within 4 sequential cohort entry blocks to account for time trend biases. The outcome DD was defined as a diagnosis of DD in secondary care or partial or total fasciotomy of wrist or hand. After a 1-year run-in period, patients were followed in an “as-treated” approach. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CIs) of incident DD among bariatric surgery patients when compared to obese unexposed patients overall, and in subgroups of age, sex, bariatric surgery type, and by duration of follow-up.Results:A total of 34 959 bariatric surgery patients were PS-matched to 54 769 obese unexposed patients. A total of 71.6% of bariatric surgery patients were women. Bariatric surgery patients had a mean age of 45.5 years and a mean follow-up of 6.9 years. All patient characteristics in obese unexposed patients were highly similar. We observed 126 and 136 severe DD cases among bariatric surgery and obese unexposed patients, respectively. The risk of DD was significantly increased in bariatric surgery patients compared to obese unexposed patients (HR = 1.30, 95% CI 1.02-1.65). The risk of DD was higher in women (HR = 1.36, 95% CI 1.00-1.84) than in men (HR = 1.05, 95% CI 0.70-1.58). Age did not modify the risk of DD among bariatric surgery patients compared to obese unexposed patients. Malabsorptive bariatric surgery yielded an increased risk of DD when compared to obese unexposed patients (HR = 1.33, 95% CI 1.04-1.71), while restrictive bariatric surgery yielded a null result. The risk of DD increased with duration of follow-up (>5 years of follow-up: HR = 1.63, 95% CI 1.14-2.34, null result in earlier follow-up).Conclusion:Our results suggest that substantial weight loss is associated with a latent increased risk of severe DD in an obese population. This observation further strengthens current evidence that high body mass index is protective against DD. The latency of risk increase of DD after bariatric surgery may suggest that slowly adapting metabolic changes may be part of the mechanism of DD emergence.References:[1]Hacquebord JH, Chiu VY, Harness NG. The Risk of Dupuytren Surgery in Obese Individuals. J Hand Surg Am. 2017, 42: 149–55.Acknowledgements:We thank Prof. Dr. Jesper Lagergren (Karolinksa Institutet, Stockholm, Sweden) for hosting Dr. Theresa Burkard for a research stay at the Upper Gastrointestinal Surgery Group and making the data available for use. Furthermore, we thank Dr. Giola Santoni (Karolinksa Institutet, Stockholm, Sweden) for her technical support.Disclosure of Interests:None declared

Background:Biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARD) may be stopped for several reasons such as non-response, adverse events, remission, or other reasons (e.g. major surgery). Understanding the reasons and consequences of b/tsDMARD therapy cessation may contribute towards therapy decision guidance. Moreover, identifying patient characteristics leading to the re-start of b/tsDMARD therapy may guide decision-making as to which patients should remain on continuous b/tsDMARD therapy versus who may potentially stop b/tsDMARD therapy.Objectives:To describe and follow rheumatoid arthritis (RA) patients who stopped b/tsDMARD therapy, stratified by cessation reason.Methods:We conducted a descriptive cohort study among adult RA patients in the longitudinal Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) between 1997 and 2019. RA patients who stopped their first b/tsDMARD therapy were eligible, with therapy stop date defining cohort entry. We followed all eligible patients from cohort entry until b/tsDMARD re-start (the outcome) or censoring due to end of patient record. All analyses were carried out stratified by cessation reason (non-response, adverse events, remission, other reasons, unknown reasons). We described patient characteristics (demographics, lifestyle factors, clinical information, other medication use, relevant comorbidities) at cohort entry. Furthermore, we estimated Kaplan Meier curves to describe differences in cumulative incidences of b/tsDMARD re-start. Finally, we assessed patient characteristics at b/tsDMARD re-start and compared them with those at cohort entry.Results:Among 2559 eligible RA patients, the majority stopped their b/tsDMARD due to non-response (982, 38%), followed by adverse events (475, 19%), other reasons (445, 17%), unknown reasons (444, 17%), and remission (213, 8%). Mean age at b/tsDMARD stop was around 56.2 years except in patients who stopped due to remission (mean age of 58.1 years). The majority of patients were women (78%), stopping due to an adverse event had the highest proportion of women (84%), stopping due to remission had the lowest proportion of women (70%). Compared to patients who stopped b/tsDMARD therapy due to non-response or adverse events, patients who stopped due to remission were generally more physically active, better educated, less likely to have a family history of rheumatic diseases, and had shorter median disease duration. A total of 2086 patients (82%) re-started b/tsDMARD therapy during follow-up. Of these, the majority did so after stopping due to non-response (94%), followed by adverse events (82%), unknown reasons (79%), other reasons (74%), and remission (47%). The median cumulative incidence of re-starting b/tsDMARD therapy was shortest after non-response (30 days), followed by unknown reasons (31 days), adverse events (94 days), other reasons (212 days), and remission (1597 days). The population who stopped b/tsDMARD therapy due to remission or other reasons yielded increased RA disease activity and an increase in proportions of women, cardiac diseases, degenerative joint disease, other auto-immune diseases, and of patients with family history of rheumatic diseases at the date of b/tsDMARD re-start. However, among patients who stopped b/tsDMARD therapy due to non-response or adverse events, patient characteristics at b/tsDMARD re-start were unchanged compared to those at b/tsDMARD stop.Conclusion:Observed differences in patient characteristics at b/tsDMARD stop may yield insight into why the patient was not responding, had an adverse event, or achieved remission. Observed changes in patient characteristics from the date of b/tsDMARD stop to re-start identified which ones may lead to a worsening of RA activity in the absence of b/tsDMARD therapy.Acknowledgements:We would like to thank Dr. Almut Scherer, Monika Hebeisen, and Eleftherios Papagiannoulis from SCQM for providing the data and answering questions thereto. A list of rheumatology offices and hospitals that are contributing to the SCQM registries can be found on www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors.Disclosure of Interests:Theresa Burkard: None declared, Enriqueta Vallejo-Yagüe: None declared, Thomas Hügle Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: GSK, Jansen, Pfizer, Abbvie, Novartis, Roche, MSD, Sanofi, BMS, Eli Lilly, UCB, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: Pfizer, BMS, Novartis, Grant/research support from: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Andrea Michelle Burden: None declared

Background:Osteoarthritis (OA) is a slowly developing chronic joint disease mainly characterized by joint pain which may lead to physical disability. OA in weight bearing joints, such as the hip and knee, was suggested to be susceptible to high body weight. In end-stage disease, hip and knee OA are often treated with arthroplasty. The impact of weight loss among obese patients on hip and knee arthroplasty has not been assessed to date.Objectives:To assess the association between bariatric surgery and hip or knee arthroplasty. As a secondary aim, we assessed the association between bariatric surgery and hip or knee OA in a secondary care setting.Methods:We performed a propensity score (PS)-matched cohort study using data from Swedish nationwide healthcare registries (patient registry [secondary care], causes of death registry, prescribed drug registry). Patients aged 18-79 years who underwent bariatric surgery between 2006 and 2019 were matched to up to 2 obese bariatric surgery free patients (called unexposed patients) based on their PS. PS-matching was carried out in risk set sampling to reduce selection bias, within 4 sequential cohort entry blocks to account for time trend biases. The primary outcome was hip or knee arthroplasty. The secondary outcome was a diagnosis of hip or knee OA in secondary care. We excluded patients with differential indications for arthroplasty or OA (e.g. rheumatoid arthritis, septic arthritis). After a 1-year run-in period, patients were followed in an “as-treated” approach until the outcome or censoring due to onset of an exclusion criterion, change of exposure status, or end of study period. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CIs) of hip or knee arthroplasty, and separately of hip or knee OA, among bariatric surgery patients when compared to obese unexposed patients. Additionally, we performed analyses in subgroups of age, sex, joint location, bariatric surgery type, and by duration of follow-up.Results:A total of 39 392 bariatric surgery patients were PS-matched to 61 085 obese unexposed patients. The study population had a mean age of 42 years, a mean follow-up of 6.5 years, and 72.5% of patients were women. We observed 1138 and 1108 hip or knee arthroplasties among bariatric surgery and obese unexposed patients, respectively. We observed an overall increased risk of hip or knee arthroplasty among bariatric surgery patients (HR of 1.43, 95% CI 1.32-1.55), compared to obese unexposed patients. The risk for knee arthroplasty was higher than that for hip arthroplasty among bariatric surgery patients (HR of 1.58, 95% CI 1.42-1.76, and HR of 1.21, 95% CI 1.06-1.39, respectively). Patients who underwent combined malabsorptive and restrictive bariatric surgery yielded highest risks of hip or knee arthroplasty (HR of 3.58, 95% CI 1.34-9.54). Risks of hip or knee arthroplasty decreased with duration of follow-up (highest risks 1-3 years post-bariatric surgery, HR of 1.79, 95% CI 1.56-2.07). In secondary analyses, risks of secondary care hip or knee OA were decreased among bariatric surgery versus obese unexposed patients (HR of 0.84, 95% CI 0.79-0.90). We observed lower risks for knee OA (HR of 0.82, 95% CI 0.76-0.88) than for hip OA (HR of 0.90, 95% CI 0.79-1.01) and observed lowest risks of hip or knee OA in early follow-up (1-3 years post-bariatric surgery) with a HR of 0.79, 95% CI 0.71-0.88, stable thereafter at a HR of 0.87, 95% CI 0.78-0.97.Conclusion:Our results suggest that substantial weight loss among obese patients is associated with decreased risks of secondary care hip and knee OA. Increased risks of hip and knee arthroplasty after bariatric surgery are likely the result of increased operability of patients who have lost a substantial amount of excess body weight. Stronger associations for the knee than for the hip in both arthroplasty and OA are consistent with existing literature suggesting a stronger impact of body weight on knee than on hip joints.Acknowledgements:We thank Prof. Dr. Jesper Lagergren (Karolinksa Institutet, Stockholm, Sweden) for hosting Dr. Theresa Burkard for a research stay at the Upper Gastrointestinal Surgery Group and making the data available for use. Furthermore, we thank Dr. Giola Santoni (Karolinksa Institutet, Stockholm, Sweden) for her technical support.Disclosure of Interests:Theresa Burkard: None declared, Dag Holmberg: None declared, Thomas Hügle Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: GSK, Jansen, Pfizer, Abbvie, Novartis, Roche, MSD, Sanofi, BMS, Eli Lilly, UCB, Andrea Michelle Burden: None declared

Background:Carpal tunnel syndrome (CTS) is a chronic compression neuropathy caused by entrapment of the median nerve in the wrist causing pain and sensory loss. Prior observational research suggested that obesity increased the risk of CTS. However, the impact of weight loss among obese patients on CTS has not been assessed to date.Objectives:To assess the association between bariatric surgery and CTS in a secondary care setting.Methods:We performed a propensity score (PS)-matched cohort study using data from Swedish nationwide healthcare registries (patient registry [secondary care], causes of death registry, prescribed drug registry). Patients aged 18-79 years who underwent bariatric surgery between 2006 and 2019 were matched to up to 2 obese bariatric surgery-free patients (called unexposed patients) based on their PS. PS-matching was carried out in risk set sampling to reduce selection bias, within 4 sequential cohort entry blocks to account for time trend biases. The outcome CTS was defined as a diagnosis of CTS in secondary care or carpal tunnel decompression surgery. After a 1-year run-in period, patients were followed in an “as-treated” approach. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CIs) of CTS among bariatric surgery patients when compared to obese unexposed patients overall, and in subgroups of age, sex, bariatric surgery type, and by duration of follow-up.Results:A total of 40 619 bariatric surgery patients were PS-matched to 63 540 obese unexposed patients. A total of 72.3% of bariatric surgery patients were women. Bariatric surgery patients had a mean age of 41.7 years and a mean follow-up of 6.8 years. All patient characteristics in obese unexposed patients were highly similar. We observed 1 356 and 1 938 severe CTS cases among bariatric surgery and obese unexposed patients, respectively. Bariatric surgery was not associated overall with CTS (HR of 0.98, 95% CI 0.91-1.05). However, the risk of CTS seemed to decrease with age at bariatric surgery – the lowest CTS risk was observed among bariatric surgery patients aged 18-34 years (HR of 0.87, 95% CI 0.74-1.01), when compared to obese unexposed patients. Sex did not modify the risk of CTS among bariatric surgery patients compared to obese unexposed patients. Restrictive bariatric surgery yielded lower risks of CTS (HRs of 0.81, 95% CI 0.69-0.88) than did malabsorptive bariatric surgery (HR of 0.95, 95% CI 0.88-1.02) when compared to obese unexposed patients. The risk of CTS increased with duration of follow-up. The lowest risk was observed 1-3 years after bariatric surgery (HR of 0.77, 95% CI 0.68-0.88) and the highest risk 6-13 years after bariatric surgery (HR of 1.20, 95% CI 1.05-1.36) when compared to obese unexposed patients.Conclusion:Our results suggest that substantial weight loss is not overall associated with severe CTS in an obese patient population. However, bariatric surgery was associated with an initial decreased risk of CTS after bariatric surgery followed by an increased risk in later follow-up. Furthermore, restrictive bariatric surgery but not malapsorptive bariatric surgery was associated with a decreased risk of CTS.Acknowledgements:We thank Prof. Dr. Jesper Lagergren (Karolinksa Institutet, Stockholm, Sweden) for hosting Dr. Theresa Burkard for a research stay at the Upper Gastrointestinal Surgery Group and making the data available for use. Furthermore, we thank Dr. Giola Santoni (Karolinksa Institutet, Stockholm, Sweden) for her technical support.Disclosure of Interests:None declared.

To describe the long-term trends in hormone therapy (HT) use in UK general practice after evidence of associated increased risks of cardiovascular disease (CVD) and breast cancer, subsequent guideline changes in 2003/2004 advising individualized HT prescribing, and halving of HT use between 2002 and 2005.We conducted a descriptive study to quantify annual proportions of overall and new HT use in women aged 40 to 79 years, using the UK-based Clinical Practice Research Datalink (1996-2015). We further described HT utilization patterns (drug type, administration route, dose) within 2-year blocks overall and within subpopulations with pre-existing CVD or breast cancer.Overall HT use continued to decline from 9.4% in 2006 to 7.5% in 2015. Between 1998 and 2001, the proportion of HT initiation was around 1.7%, which halved by 2005 (0.8%), and increased again up until 2015 (1.0%). The mean age of HT users increased from 54.7 in 1996/1997 to 56.6 in 2002/2003, and leveled off at 57 to 58 years in 2014/2015. The prevalence of CVD in HT users decreased from a peak of 5.8% in 2002/2003 to 4.5% in 2014/2015, whereas breast cancer prevalence continuously increased from 0.9% in 1996/1997 to 1.9% in 2014/2015. Overall, we observed trends towards use of estrogen therapy, vaginal HT, and lower HT dose after 2002/2003, which were stronger among subpopulations with pre-existing CVD or breast cancer.Our study suggests that the HT guideline changes implemented in UK clinical practice resulted in safer HT use, particularly in women with pre-existing CVD or breast cancer.

Objective To investigate the association between statin therapy initiation and incident hand osteoarthritis (OA). Methods We performed a propensity score-matched cohort study using data from the UK-based Clinical Practice Research Datalink. Statin initiators had ≥1 statin prescription between 1996 and 2015 and were matched 1:1 on their propensity score to noninitiators within 10 sequential 2-year cohort entry blocks. After a 180-day run-in period, patients were followed in an as-treated approach until a recorded diagnosis of hand OA or until censoring (change in exposure status, development of an exclusion criterion, or maximum follow-up of 5.5 years). We applied Cox proportional hazard regression to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs) overall and in subgroups of sex, age, statin dose, statin agent, preexisting dyslipidemia, and treatment duration. To compare results, we ran all analyses with negative and positive control outcomes and assessed generalized OA as a secondary outcome. We further performed the overall analysis with an active comparator (topical glaucoma therapy initiators). Results Among 233,608 statin initiators and the same number of noninitiators, we observed an overall HR for hand OA of 0.98 (95% CI 0.88-1.09). The observed null result remained unchanged in all subgroups. Results were highly similar for generalized OA and negative control outcomes. In addition, the active comparator analysis showed a null result with an HR for hand OA of 0.85 (95% CI 0.56-1.29). Previously known associations with positive control outcomes were observed. Conclusion There was no association between statin initiation and incident hand OA in this study.

Objective To estimate the risk of hand osteoarthritis (HOA) associated with hormone replacement therapy (HRT). Methods We conducted a nested case-control study using data from the UKbased Clinical Practice Research Datalink (1998–2017). In the study inception cohort comprised women at age 45. We matched women with incident HOA during follow-up (cases) to osteoarthritisfree controls on age and calendar date (index date, ID), in a ratio of 1:4. We applied conditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI) of HOA associated with new HRT use compared with non-use overall, and for women with recorded menopause we calculated separate ORs according to the time between menopause and HRT initiation (current users), and the time between HRT cessation and the ID (past users), versus non-users. Results There were 3440 cases and 13,760 controls (mean age: 50.9 ± 4.1 years). We observed an adjusted OR (aOR) of HOA of 1.32 (95 % CI 1.17–1.48) in HRT users (versus nonusers), which attenuated to 0.98 (95 % CI 0.85–1.14) in women with recorded menopause. Current users (versus nonusers) who initiated HRT 3 months before or after menopause had an aOR of 0.72 (95 % CI 0.55–0.96), while aORs increased with later HRT initiation. Among past users (versus non-users), we observed an aOR of 1.25 (95 % CI 0.86–1.81) when HRT use was stopped ≤18 months before the ID, approaching the null with increasing duration between HRT cessation and the ID. Conclusion Current HRT use was associated with a decreased risk of HOA if initiated around menopause, but the risk reduction disappeared after HRT cessation.