Search

Objective: This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA)., Methods: This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m 2 . All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) <2.6 stratified by BMI., Results: Out of 793 people included in the present report, 161 (20%) had obesity at baseline. During follow-up, participants with baseline obesity had higher disease activity compared with those with lower BMI, despite having similar disease activity at baseline. In survival analyses, obesity was associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The effect of obesity on response to treatment was not influenced by the treatment arms., Conclusion: In people with untreated early RA followed up for up to 48 weeks, obesity was associated with a lower likelihood of good treatment response, irrespective of the type of randomised treatment received., Trial Registration Number: NCT01491815., Competing Interests: Competing interests: MLH reports research grants from AbbVie, iogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk to institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Medac, Sandoz paid to institution; participation on a Data Safety Monitoring Board or Advisory Board from AbbVie paid to institution; MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies; MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylarthritis based on secondary data and is partly funded by Novartis. DN reports personal consultancy fees from BMS, Lilly, MSD, Novartis, Pfizer and UCB, and personal study grant from MSD, outside current work. BG reports consulting fee from Novartis and Lectures fees from Novartis and Nordic Pharma. MØ reports grants from Amgen, BMS, Merck, Celgene and Novartis to institution; consulting fees from Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB; support for attending meetings and/or travel from UCB; participation on a Data Safety Monitoring Board or Advisory Board from Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB. TS-I reports research grant from Amgen paid to the institution, honoraria from Nordic Pharma. TU reports personal fees from Galapagos, Lilly, Pfizer, UCB outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Adiponectin, leptin, and resistin are thought to be involved in the pathogenesis of rheumatoid arthritis (RA). However, the causal relationship between these adipokines and the risk for RA is unclear. We performed a range of two-sample Mendelian randomisation (MR) analyses to assess the causal effect of circulating adiponectin, leptin, and resistin on RA risk in European and East Asian individuals. Different sets of adiponectin-, leptin-, and resistin-related genetic variants were used as instruments for genetically determined adipokine levels. As body mass index (BMI) is a risk factor for RA and affects adipokine levels, multivariable MR was used to calculate the causal effect of each adipokine on RA risk taking BMI into account. Several MR analyses revealed no evidence of a causal relationship between circulating adiponectin, leptin, or resistin levels and RA risk in either Europeans or East Asians. Similarly, multivariable MR did not provide evidence of any causal effect of adiponectin, leptin, or resistin on RA risk when taking BMI into account. This MR study shows for the first time that genetically determined levels of adiponectin, leptin, or resistin do not have a direct causal effect on the risk of developing RA after adjustment for BMI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vasileiadis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (β = 0.344, p = 0.021), CCL2 (β = 0.342, p = 0.012), and CXCL9 (β = 0.308, p = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (β = 0.308, p = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (β = 0.485, p = 0.001; β = 0.463, p = 0.001) and erythrocyte sedimentation rate (β = 0.442, p = 0.001; β = 0.507, p < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.

Objective The aim of the current study is to determine whether baseline serum adiponectin levels predict the development of rheumatoid arthritis (RA). Method The current report includes 3693 individuals from the Swedish Obese Subjects (SOS) study. The original SOS study is a longitudinal non-randomized controlled study aiming to assess the effect of bariatric surgery on obesity-related mortality and morbidity. Participants included in the present report had adiponectin measurement available at baseline and no prevalent RA. The diagnosis of RA was retrieved through the Swedish National Patient Register. Results During a follow-up for up to 29 years, 82 study participants developed RA. Elevated baseline adiponectin levels were associated with a higher risk of developing RA independently of other factors, including C-reactive protein (CRP) and smoking [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.12-2.60 for an increase in adiponectin of 10 mg/L, p = 0.01]. After stratifying the population according to adiponectin and CRP median at baseline, study participants with both adiponectin and CRP above the median had a higher risk of developing RA compared to subjects with adiponectin and CRP below the median (HR 2.80, 95% CI 1.25-6.31, p = 0.01). Conclusions In this cohort of subjects with obesity followed up for up to 29 years, high serum adiponectin levels at baseline were associated with an increased risk for RA. Moreover, subjects with both high adiponectin and CRP levels at baseline were at particular risk of developing RA. ClinicalTrials.gov Identifier: NCT01479452.

Objective: The aim of this study was to determine the effect of bariatric surgery on the incidence of RA in participants of the Swedish Obese Subjects (SOS) study., Methods: The SOS is a longitudinal study aiming to assess the effect of bariatric surgery on mortality and obesity-related diseases. This report includes 2002 subjects with obesity who underwent bariatric surgery and 2034 matched controls; none of them had RA at baseline. Cases of incident RA were identified through the Swedish National Patient Register by searching for International Classification of Diseases codes. Both intention-to-treat analyses and per-protocol analyses are reported. In the per-protocol analysis, participants from the control group who underwent bariatric surgery later on during follow-up were censored at the time of surgery., Results: During follow-up, 92 study participants developed RA. The median follow-up was 21 years (range 0-29). Bariatric surgery was neither associated with the incidence of RA in the intention-to-treat analysis [hazard ratio (HR) 0.92 (95% CI 0.59, 1.46), P = 0.74], nor in the per-protocol analysis [HR 0.86 (95% CI 0.54, 1.38), P = 0.53]. Weight change at the 2 year follow-up, expressed as the change in BMI compared with baseline, did not associate with the development of RA. Higher serum CRP levels and smoking associated with the future development of RA independent of other factors., Conclusions: We did not detect any association between bariatric surgery and the incidence of RA in subjects affected by obesity followed up for up to 29 years., Clinicaltrials.gov: (http://clinicaltrials.gov): NCT01479452., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)