Comparative effectiveness of biologics in patients with rheumatoid arthritis stratified by body mass index: a cohort study in a Swiss registry.

OBJECTIVES Obesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). In patients with obesity, abatacept was suggested as a preferable option to tumour necrosis factor-alpha inhibitors. We aimed to assess the comparative effectiveness of etanercept, infliximab and abatacept, compared with adalimumab, in patients with RA with obesity. Secondarily, we also investigated this in patients with overweight and normal weight for completeness. DESIGN Observational cohort study. SETTING Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997-2019). PARTICIPANTS Adult patients with RA from the SCQM registry who received etanercept, infliximab, abatacept or adalimumab as their first biological or targeted synthetic disease-modifying antirheumatic drug were classified based on their body mass index (BMI) at the start of that treatment in three cohorts: obese, overweight, normal weight. They were followed for a maximum of 1 year. EXPOSURE The study exposure of interest was the patients' first biological, particularly: etanercept, infliximab and abatacept, compared with adalimumab. PRIMARY AND SECONDARY OUTCOME MEASURES The primary study outcome was remission within 12 months, defined as 28-joint Disease Activity Score (DAS28) <2.6. Missingness was addressed using confounder-adjusted response rate with attrition correction. Logistic regression was used to compare the effectiveness of etanercept, infliximab and abatacept versus adalimumab. Each BMI cohort was addressed and analysed separately. RESULTS The study included 443 obese, 829 overweight and 1243 normal weight patients with RA. There were no statistically significant differences in the odds of DAS28-remission at ≤12 months for etanercept, infliximab and abatacept, compared with adalimumab, in any of the BMI cohorts. CONCLUSIONS No differences in DAS28-remission were found between the study drugs and adalimumab as first biologic in patients with RA, independently of the BMI cohort. We did not find evidence that treatment with abatacept increased the likelihood of remission compared with adalimumab among obese patients with RA

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

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

JAK-inhibitors and risk on serious viral infection, venous thromboembolism and cardiac events in patients with rheumatoid arthritis:A protocol for a prevalent new-user cohort study using the Danish nationwide DANBIO register

Janus Kinase inhibitors (JAKis) are targeted synthetic disease-modifying antirheumatic drugs and represent an important alternative to treat patients with moderate to high rheumatoid arthritis (RA) disease activity. Safety concerns associated with increased risk for venous thromboembolism (VTE), serious viral infection, and, more recently, major adverse cardiovascular events (MACE) in JAKi users have emerged worldwide. However, as the exact mechanisms to explain these safety concerns remain unclear, the increased risk of VTE, MACE, and serious viral infection in JAKi users is heavily debated. In light of the need to enrich the safety profile of JAKis in real-world data, we aim to quantify the incidence and risk of MACE, VTE, and serious viral infections in RA patients registered in the Danish DANBIO registry, a nationwide registry of biological therapies used in rheumatology. Therefore, we will conduct a population-based cohort study using a prevalent new-user design. We will identify all RA patients in the DANBIO, ≥ 18 years old, receiving a JAKi or a tumor necrosis factor α inhibitor (TNF-αi) from January 2017 to December 2022. Prevalent and new users of JAKis will be matched to TNF-αi comparators with similar exposure history using time-conditional propensity scores (TCPS). We will describe the cumulative incidence of the outcomes (VTE, MACE, serious viral infection) in each exposure group (JAKi users; TNF-αi users), stratified by outcome type. Additionally, the Aalen-Johansen method will be used to estimate the time-to-event survival function stratified by outcome type. We will also estimate the hazard ratio (HR) with 95% confidence interval (CI) of each outcome in both exposure groups using the time-dependent Cox proportional hazards model. Results will enrich the safety profile of JAKis in real-world data

Lower odds of remission among women with rheumatoid arthritis: A cohort study in the Swiss Clinical Quality Management cohort

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

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications

Although sex and gender are recognized as major determinants of health and immunity, their role israrely considered in clinical practice and public health. We identified six bottlenecks preventing theinclusion of sex and gender considerations from basic science to clinical practice, precision medicineand public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex andgender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-relatedbottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and genderidentity. (iii) A translational bottleneck, limited by animal models and the underrepresentation ofgender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statisticalanalyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation ofpregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemicbias and discriminations affect not only academic research but also decision makers. We specifyguidelines for researchers, scientific journals, funding agencies and academic institutions to addressthese bottlenecks. Following such guidelines will support the development of more efficient andequitable care strategies for all

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications.

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all

Drug Triggers and Clinic of Acute Generalized Exanthematous Pustulosis (AGEP): A Literature Case Series of 297 Patients

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were &ge;25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging

Comparison of Psoriatic Arthritis and Rheumatoid Arthritis Patients across Body Mass Index Categories in Switzerland.

Abnormal body mass index (BMI) was associated with worse rheumatic markers in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Aiming to describe PsA and RA patients stratified by BMI, we performed a descriptive study in PsA and RA patients (two distinct cohorts) in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry. New users of biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) were stratified by BMI at the start of their treatment (underweight, normal weight, overweight, obese). The PsA underweight and normal weight categories were merged. Age at disease onset and further characteristics at the start of the first b/tsDMARD treatment were compared across BMI categories vs. the corresponding normal weight group. The study included 819 PsA (36.5% overweight, 23.8% obese) and 3217 RA patients (4.4% underweight, 31.8% overweight, 17.0% obese). Compared to the corresponding normal weight group, PsA and RA obese patients had significantly (p < 0.05) higher C-reactive protein, worse disease activity, and lower quality of life (QoL). Obese PsA patients had significantly worse skin manifestation and pain, while obese RA patients had significantly higher erythrocyte sedimentation rate and tender joint counts, as well as lower seropositive prevalence. To conclude, obese PsA and RA patients presented worse disease activity and poorer QoL than those with normal weight