The risk of inflammatory bowel disease in patients with axial spondyloarthritis treated with biologic agents : BSRBR-AS and meta-analysis

Funding: The BSRBR-AS is supported by the British Society for Rheumatology and they have received funds for the registry from Pfizer, AbbVie and UCB. These companies have no input in determining the topics for analysis or work involved in undertaking it but do receive an advance copy of the manuscript on which they may make comments. ACKNOWLEDGEMENTS: The original idea for the study was suggested by John Mansfield and discussed with Lesley Kay (both Newcastle upon Tyne Hospitals NHS Foundation Trust). All authors discussed and contributed to designing this study and the analysis plan, which was undertaken by RLB and (updated and) overseen by OR, LED and GJM. Results were reviewed by all authors. GJM, RLB, OR and LED all contributed to drafting the manuscript which was critically reviewed by all authors. RLB undertook this work while a visiting student based at the University of Aberdeen from Ludwig-Maximilians Universität (Munich).Peer reviewedPostprin

Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis

Acknowledgment We are grateful to Professor Gary Macfarlane for commenting on the manuscript. We are grateful to the staff of the BSRBR-AS register and to the recruiting staff at the clinical centres, details of which are available at: www.abdn.ac.uk/bsrbr-as. We also thank Dr Lewis Carpenter for suggesting splines for modelling time. Contribution: SSZ analysed the data and wrote the manuscript with significant input from all co- authors. GTJ is the Deputy Chief Investigator on BSRBR-AS and designed the study and oversaw its conduct. In the current project they discussed results and provided input into drafts of the manuscript. Funding: The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it.Peer reviewedPublisher PD

Comorbidity and response to TNF inhibitors in axial spondyloarthritis : longitudinal analysis of the BSRBR-AS

Acknowledgements: Funding: The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it. Disclosures: The authors declare no conflicts of interest. Contribution: SSZ analysed the data and wrote the manuscript, with significant input from all coauthors. GJM and GTJ are Chief Investigator and Deputy Chief Investigator respectively on BSRBR-AS and designed the study and oversaw its conduct. In the current project they discussed results and provided input into drafts of the manuscript. Data availability: Data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis are available to external investigators, on reasonable request. For information on how to access data, see: http://www.rheumatology.org.uk. We are grateful to the staff of the BSRBR-AS register and to the recruiting staff at the clinical centres, details of which are available at: www.abdn.ac.uk/bsrbr-asPeer reviewedPublisher PD

Association between comorbidities and disease activity in axial spondyloarthritis : results from the BSRBR-AS

Funding: The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it. We are grateful to the staff of the BSRBR-AS register and to the recruiting staff at the clinical centres, details of which are available at: http://www.abdn.ac.uk/bsrbr-as S.S.Z. analysed the data and wrote the manuscript, with significant input from all co-authors. G.J.M. and G.T.J. are Chief Investigator and Deputy Chief Investigator, respectively, on BSRBR-AS and designed the study and oversaw its conduct. In the current project they discussed results and provided input into drafts of the manuscript. Disclosure statement: The authors have declared no conflicts of interest.Peer reviewedPublisher PD

Impact of Smoking in Response to Tumor Necrosis Factor Inhibitors in Axial Spondyloarthritis : Methodologic Considerations for Longitudinal Observational Studies

We are grateful to Professor Gary Macfarlane (Chief Investigator of BSRBR-AS), the staff of the BSRBR-AS (Claudia Zabke, Elizabeth Ferguson-Jones, Maureen Heddle, Nafeesa Nazlee, and Barry Morris), and the recruiting staff at the clinical centers.Peer reviewedPostprin

Association of Diverticulitis with Prolonged Spondyloarthritis: An Analysis of the ASAS-COMOSPA International Cohort

This study examined the relationship between spondyloarthritis (SpA) duration and gastrointestinal comorbidities other than inflammatory bowel disease (IBD). We evaluated the association between SpA duration and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis using data from a large international cross-sectional study. Binary regression models were created, adjusted for age, sex, body mass index (BMI), smoking, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, IBD history and country. Subgroup analysis was performed by disease phenotype. The data of 3923 participants were analysed. The prevalence of gastrointestinal conditions were 10.7% upper gastrointestinal ulcers; 4.7% viral hepatitis and 1.5% diverticulitis. While SpA duration was not associated with upper gastrointestinal ulcers, HBV or HCV, longer SpA duration was significantly associated with diverticulitis (odds ratios (OR) = 1.18, 95% confidence interval (CI): 1.03–1.34), reflecting an 18% increase for every five years of SpA duration. Other significant associations with diverticulitis were age and high alcohol intake but not medication history. In subgroup analyses, the association was strongest with those with axial SpA. The reasons for this association of increased diverticulitis with disease duration in SpA, especially those with axial disease, are unclear but may reflect shared underlying gut inflammation. Diverticulitis should be considered, in addition to IBD, when SpA patients present with lower gastrointestinal symptoms

Smoking status and cause-specific discontinuation of tumour necrosis factor inhibitors in axial spondyloarthritis

Availability of data and materials BSRBR-AS data are held at the University of Aberdeen. Funding The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it. SZ was supported by awards from the Royal College of Physicians (John Glyn bursary) and Royal Society of Medicine (Kovacs fellowship). KY received financial support for his doctoral study from the Pharmacoepidemiology Program at the Harvard T.H. Chan School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer and ASISA) and Honjo International Scholarship Foundation. DHS was supported by grants from the National Institute of Health (NIH-P30-AR072577 (VERITY) and NIH-K24AR055989) and has received funding from Abbvie and Amgen unrelated to this work. Acknowledgements We are grateful to Professor Gary Macfarlane (Chief Investigator of BSRBR-AS) and the staff of the BSRBR-AS register who are currently Claudia Zabke, Elizabeth Ferguson-Jones, Maureen Heddle, Nafeesa Nazlee and Barry Morris, and to the recruiting staff at the clinical centres, details of which are available at: https://www.abdn.ac.uk/iahs/research/epidemiology/spondyloarthritisPeer reviewedPublisher PD

Autoantibodies to Osteoprotegerin are Associated with Low Hip Bone Mineral Density and History of Fractures in Axial Spondyloarthritis: A Cross-Sectional Observational Study

Osteoporosis is a recognised complication of axial spondyloarthritis (axSpA) and is thought to be due to functional impairment and the osteoclast-activating effects of proinflammatory cytokines. The development of autoantibodies to OPG (OPG-Ab) has been associated with severe osteoporosis and increased bone resorption in rheumatoid arthritis. In this study, we screened for the presence of OPG-Ab in axSpA and reviewed their clinical significance. We studied 134 patients, recruited from two centres in the United Kingdom. Their mean age was 47.5 years and 75% were male. Concentrations of OPG-Ab were related to bone mineral density (BMD) and fracture history using linear and logistic regression models adjusting for age, gender, disease duration and activity, body mass index and bisphosphonate use. We detected OPG-Ab in 11/134 patients (8.2%). Femoral neck and total hip BMD were significantly reduced in OPG-Ab positive patients (0.827 vs. 0.967 g/cm2, p = 0.008 and 0.868 vs. 1.028 g/cm2, p = 0.002, respectively). Regression analysis showed that the presence of OPG-Ab was independently associated with total hip osteopenia (ORadj 24.2; 95% CI 2.57, 228) and history of fractures (ORadj 10.5; 95% CI 2.07, 53.3). OPG-Ab concentration was associated with total hip BMD in g/cm2 (ß = −1.15; 95% CI −0.25, −0.04). There were no associations between OPG-Ab concentration and bone turnover markers, but free sRANKL concentrations were lower in OPG-Ab-positive patients (median 0.04 vs. 0.11 pmol/L, p = 0.050). We conclude that OPG-Ab are associated with hip BMD and fractures in axSpA suggesting that they may contribute to the pathogenesis of bone loss in some patients with this condition