Theresa Burkard

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Burkard

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Theresa

ORCID

0000-0003-1313-4473

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Publications 1 - 10 of 17

Minimal disease activity and remission in patients with psoriatic arthritis with elevated body mass index: an observational cohort study in the Swiss Clinical Quality Management cohort
Vallejo-Yagüe, Enriqueta; Burkard, Theresa; Micheroli, Raphael; et al. (2022)
BMJ Open
Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
Patient groups in Rheumatoid arthritis identified by deep learning respond differently to biologic or targeted synthetic DMARDs
Kalweit, Maria; Burden, Andrea; Boedecker, Joschka; et al. (2023)
PLoS Computational Biology
Cycling of biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA) patients due to non-response is a problem preventing and delaying disease control. We aimed to assess and validate treatment response of b/tsDMARDs among clusters of RA patients identified by deep learning. We clustered RA patients clusters at first-time b/tsDMARD (cohort entry) in the Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) [1999-2018]. We performed comparative effectiveness analyses of b/tsDMARDs (ref. adalimumab) using Cox proportional hazard regression. Within 15 months, we assessed b/tsDMARD stop due to non-response, and separately a >= 20% reduction in DAS28-esr as a response proxy. We validated results through stratified analyses according to most distinctive patient characteristics of clusters. Clusters comprised between 362 and 1481 patients (3516 unique patients). Stratified (validation) analyses confirmed comparative effectiveness results among clusters: Patients with >= 2 conventional synthetic DMARDs and prednisone at b/tsDMARD initiation, male patients, as well as patients with a lower disease burden responded better to tocilizumab than to adalimumab (hazard ratio [HR] 5.46, 95% confidence interval [CI] [1.76-16.94], and HR 8.44 [3.43-20.74], and HR 3.64 [2.04-6.49], respectively). Furthermore, seronegative women without use of prednisone at b/tsDMARD initiation as well as seropositive women with a higher disease burden and longer disease duration had a higher risk of non-response with golimumab (HR 2.36 [1.03-5.40] and HR 5.27 [2.10-13.21], respectively) than with adalimumab. Our results suggest that RA patient clusters identified by deep learning may have different responses to first-line b/tsDMARD. Thus, it may suggest optimal first-line b/tsDMARD for certain RA patients, which is a step forward towards personalizing treatment. However, further research in other cohorts is needed to verify our results.
Increased Risk of Fracture Among Patients With Iron Overload: A Population-based Matched Cohort Study
Burden, Andrea Michelle; Martinez de la Torre, Adrian; Burkard, Theresa; et al. (2025)
The Journal of Clinical Endocrinology & Metabolism
Introduction: Iron overloading disorders are associated with decreased bone mineral density. However, evidence on fracture risk is scarce. Therefore, we evaluated the risk of fracture associated with iron overload disorders compared to matched controls. Methods: Using The Healthcare Improvement Network, a Cegedim database of UK general practice data, we identified patients >18 years with elevated iron (ferritin value >1000 mu g/L) or an eligible diagnosis code for iron overloading disorders between 2010 and 2022. The first date of elevated iron or a diagnosis code defined the index date for iron overload patients, who were matched with up to 10 controls. Time-varying confounder-adjusted Cox proportional hazard models estimated the hazard ratios (HRs) and 95% confidence intervals. Analyses were stratified by osteoporotic fracture site (hip, vertebral, humerus, forearm) and evidence of elevated serum ferritin at baseline (ferritin >1000 mu g/L), and sex. Results: We identified 20 264 eligible patients and 192 956 controls. Overall, there was a 55% increased risk of any fracture among iron overload patients (HR 1.55 [1.42-1.68]). Fracture risk was increased at all sites, with the highest risk observed for vertebral fractures (HR 1.97 [1.63-2.10]). Patients with ferritin >1000 mu g/L had a 91% increased risk of any fracture (HR 1.91 [1.73-2.16]) and a 2.5-fold increased risk of vertebral fractures (HR 2.51 [2.01-3.12]). There was no increased risk among patients without elevated serum ferritin at any site. Fracture risk was similar between sexes. Discussion: This large population-based cohort study found a 55% increased risk of fracture associated with iron overload. The risk was highest among patients with laboratory-confirmed iron overload, highlighting the importance for clinicians to consider initiating osteoporosis therapy in patients with serum ferritin >1000 mu g/L to minimize fracture risk.
Prediction of sustained biologic and targeted synthetic DMARD-free remission in rheumatoid arthritis patients
Burkard, Theresa; Williams, Ross D.; Vallejo-Yagüe, Enriqueta; et al. (2021)
Rheumatology Advances in Practice
Objectives The aim was to develop a prediction model of sustained remission after cessation of biologic or targeted synthetic DMARD (b/tsDMARD) in RA. Methods We conducted an explorative cohort study among b/tsDMARD RA treatment episode courses stopped owing to remission in the Swiss Clinical Quality Management registry (SCQM; 2008–2019). The outcome was sustained b/tsDMARD-free remission of ≥12 months. We applied logistic regression model selection algorithms using stepwise, forward selection, backward selection and penalized regression to identify patient characteristics predictive of sustained b/tsDMARD-free remission. We compared c-statistics corrected for optimism between models. The three models with the highest c-statistics were validated in new SCQM data until 2020 (validation dataset). Results We identified 302 eligible episodes, of which 177 episodes (59%) achieved sustained b/tsDMARD-free remission. Two backward and one forward selection model, with eight, four and seven variables, respectively, obtained the highest c-statistics corrected for optimism of c = 0.72, c = 0.70 and c = 0.69, respectively. In the validation dataset (47 eligible episodes), the models performed with c = 0.99, c = 0.80 and c = 0.74, respectively, and excellent calibration. The best model included the following eight variables (measured at b/tsDMARD stop): RA duration, b/tsDMARD duration, other pain/anti-inflammatory drug use, quality of life (EuroQol), DAS28-ESR score, HAQ score, education, and interactions of RA duration and other pain/anti-inflammatory drug use and of b/tsDMARD duration and HAQ score. Conclusion Our results suggest that models with up to eight unique variables may predict sustained b/tsDMARD-free remission with good efficiency. External validation is warranted.
The association of bariatric surgery and Dupuytren's disease: a propensity score-matched cohort study
Burkard, Theresa; Lane, Jennifer C.E.; Holmberg, Dag; et al. (2022)
Journal of Hand Surgery (European Volume)
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.
Lower odds of remission among women with rheumatoid arthritis: A cohort study in the Swiss Clinical Quality Management cohort
Vallejo-Yagüe, Enriqueta; Pfund, Julia N.; Burkard, Theresa; et al. (2022)
PLoS ONE
Objective To compare the likelihood of achieving remission between men and women with rheumatoid arthritis (RA) after starting their first biologic or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD). Methods This cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included RA patients starting their first b/tsDMARD (1997-31/04/2018). The odds of achieving remission at ≤12-months, defined by disease activity score 28-joints (DAS28) <2.6, were compared between men and women. Secondary analyses were adjusted for age and seropositivity, and we investigated potential mediators or factors that could explain the main findings. Results The study included 2839 (76.3%) women and 883 (23.7%) men with RA. Compared to women, men were older at diagnosis and b/tsDMARD start, but had shorter time from diagnosis to b/tsDMARD (3.4 versus 5.0 years, p<0.001), and they had lower DAS28 at b/ tsDMARD start. Compared to women, men had 21% increased odds of achieving DAS28-remission, with odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02–1.42. Adjusting for age and seropositivity yielded similar findings (adjusted OR 1.24, 95%CI 1.05–1.46). Analyses of potential mediators suggested that the observed effect may be explained by the shorter disease duration and lower DAS28 at treatment initiation in men versus women. Conclusion Men started b/tsDMARD earlier than women, particularly regarding disease duration and disease activity (DAS28), and had higher odds of reaching remission. This highlights the importance of early initiation of second line treatments, and suggests to target an earlier stage of disease in women to match the benefits observed in men.
The associations between bariatric surgery and hip or knee arthroplasty, and hip or knee osteoarthritis: Propensity score-matched cohort studies
Burkard, Theresa; Holmberg, Dag; Wretenberg, Per; et al. (2022)
Osteoarthritis and Cartilage Open
Objective To investigate the associations between bariatric surgery and hip or knee arthroplasty, and secondary care hip or knee osteoarthritis (OA). Methods We performed cohort studies using data from Swedish nationwide healthcare registries. Patients aged 18–79 years who underwent bariatric surgery between 2006 and 2019 were matched on their propensity score (PS) to up to 2 obese patients (“unexposed episodes”) in risk-set sampling. After a 1-year run-in period, episodes were followed in an “as-treated” approach. Using Cox proportional hazard regression, we calculated hazard ratios (HR) with 95% confidence intervals (CIs) of hip or knee arthroplasty overall and in subgroups of age, sex, joint location, arthroplasty type, bariatric surgery type, and by duration of follow-up if proportional hazard assumptions were violated. In a secondary cohort, we assessed the outcome incident secondary care hip or knee osteoarthritis (OA). Results Among 39‘392 bariatric surgery episodes when compared to 61’085 PS-matched unexposed episodes (47′594 unique patients), the risk of hip or knee arthroplasty was strongest increased within the first three years of follow-up (HR 1.79, 95% CI 1.56–2.07), decreased thereafter, but remained elevated throughout follow-up. In a secondary cohort of 37′929 exposed when compared to 58′600 PS-matched unexposed episodes, the risk of hip or knee osteoarthritis was decreased (HR 0.84, 95% CI 0.79–0.90). Conclusion Bariatric surgery is associated with increased risks of hip or knee arthroplasty, but also with decreased risks of secondary care OA. This contradiction supports the hypothesis that bariatric surgery may act as an enabler for hip or knee arthroplasty.
Identification of polypharmacy patterns in new‐users of metformin using the Apriori algorithm: A novel framework for investigating concomitant drug utilization through association rule mining
Faquetti, Maria Luisa; Martinez de la Torre, Adrian; Burkard, Theresa; et al. (2023)
Pharmacoepidemiology and Drug Safety
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.
The association of bariatric surgery and carpal tunnel syndrome: A propensity score-matched cohort study
Lane, Jennifer; Holmberg, Dag; Thorell, Anders; et al. (2024)
Journal of Plastic, Reconstructive and Aesthetic Surgery
Objectives: To test the hypothesis that weight loss following bariatric surgery is associated with a reduced risk of developing carpal tunnel syndrome (CTS) compared with obese patients who do not undergo bariatric surgery. Methods: We performed a cohort study using data from the Swedish nationwide healthcare registries. Patients aged 18–79 years who underwent bariatric surgery from 2006 to 2019 were propensity score (PS)–matched to up to 2 obese bariatric surgery-free patients (“unexposed patients”). Cox proportional hazard regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CIs) to compare the incidence of CTS among bariatric surgery patients to obese unexposed patients both overall and divided by subgroups of age, sex, bariatric surgery type, and duration of follow-up. Results: In total, 40,619 bariatric surgery patients were PS-matched to 63,540 obese unexposed patients who did not undergo surgery. Bariatric surgery was not associated overall with CTS (HR 0.98, 95% CI 0.91–1.05). There was a 23% decreased risk of CTS incidence observed within >1–3 years after bariatric surgery (HR 0.77, 95% CI 0.68–0.88). Decreased CTS risks were observed among bariatric surgery patients aged 18–34 years (HR 0.87, 95% CI 0.74–1.01) and those who underwent sleeve gastrectomy (HR 0.81, 95% CI 0.63–1.03), but these risks did not reach significance level compared with obese unexposed patients. However, there was a 20% increased CTS risk after 6 years (HR 1.20, 95% CI 1.05–1.36). Conclusion: Our results suggest that marked weight does not have a lasting impact on the reduction of CTS incidence.
Validity of bariatric surgery codes in the UK Clinical Practice Research Datalink (CPRD) GOLD compared with Hospital Episodes Statistics
Burkard, Theresa; Rauch, Marlene; Jick, Susan S.; et al. (2021)
Pharmacoepidemiology and Drug Safety
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 (ie, 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 (ie, 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.

Publications 1 - 10 of 17

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