AB0228 GABAPENTINOID USE AND THE RISK OF FRACTURES IN PEOPLE WITH INFLAMMATORY ARTHRITIS: NESTED CASE-CONTROL STUDY IN THE CLINICAL PRACTICE RESEARCH DATALINK (CPRD) AURUM

Scott, I.; Daud, N.; Bailey, J.; Twohig, H.; Hider, S.; Mallen, C.; Jordan, K.; Muller, S.

Abstract

Background: Recent observational studies suggest gabapentinoids associate with an increased risk of fractures. The potential for confounding inherent to non-randomised studies of interventions, however, alongside the conflicting findings of these studies (with some reporting an increased risk [1] and others no relationship [2] mean further confirmatory research is needed. We therefore conducted a case-control study in people with inflammatory arthritis (IA) – a population often suffering fractures and widely prescribed gabapentinoids – in which all people had received a gabapentinoid at some point, minimising confounding by indication. Objectives: To determine the risk of fractures in people with IA currently and recently receiving a gabapentinoid prescription, compared to those receiving one in the remote past. Methods: We used data from CPRD Aurum (primary care electronic health record database covering 20% of England) and linked Hospital Episode Statistics Admitted Patient Care data. Adults meeting validated criteria for a rheumatoid arthritis/psoriatic arthritis/axial spondyloarthritis diagnosis and contributing data to Aurum between 01/01/2004 and 31/12/2022, entered the cohort on first receipt of an oral gabapentinoid prescription. Cases had a coded diagnosis of an incident fracture after cohort inclusion. Risk set sampling matched them to up to five controls (on age, gender, and gabapentinoid type). Gabapentinoid exposure was categorised as: (a) current (prescription overlapped with fracture date); (b) recent (prescription ended 1 to 60 days pre-fracture date); and (c) remote (prescription ended >60 days pre-fracture date). Conditional logistic regression models determined odds ratios (ORs) with 95% confidence intervals (CIs) for fractures with current or recent gabapentinoid use vs. remote use, adjusting for confounding variables age, gender, IA type, previous fragility fracture(s)/presence of osteoporosis, presence of CKD stage III/IV/V, prednisolone use, and receipt of a current opioid prescription. Analysis was repeated stratifying exposure by gabapentinoid type and dose, and duration of current use. Results: 2,529 cases and 12,466 controls were included. More cases received gabapentin (1,526) than pregabalin (941) and more were remote (65.0%) than current (29.5%) or recent (5.5%) users (similar patterns in controls). Current any gabapentinoid use (vs. remote use) associated with a significantly increased fracture risk (OR 1.35 [95% CI 1.22, 1.50]). Similar risks were seen with gabapentin (OR 1.31 [1.13, 1.52]) and pregabalin (OR 1.44 [1.22, 1.70]). Recent use of any gabapentinoid, gabapentin, and pregabalin also associated with a significantly increased fracture risk with ORs of 1.47 (1.20, 1.81), 1.38 (1.04, 1.81), and 1.61 (1.13, 2.30). Examining risk by dosing showed that for gabapentin, the association was only observed with low dose current use (OR 1.42 [1.15, 1.75]); this may have arisen from confounding by use duration (with gabapentin requiring up-titration, and therefore low dose use more likely in those starting gabapentin more recently). For pregabalin, a significantly increased risk of fractures was seen for low (OR 1.68 [1.27, 2.24]), moderate (OR 1.35 [1.09, 1.67]), and high (OR 1.40 [1.06, 1.85]) dose current use. Examining risk by duration of use revealed strongest associations for those currently using gabapentinoids for <12-months. Conclusion: In people with IA, the risk of fractures is significantly increased in those currently using gabapentinoids, after accounting for both measured (through model adjustment) and time-invariant unmeasured (through comparing risk to remote gabapentinoid users) confounding. When considered alongside a lack of evidence for efficacy and widespread prescribing - with 10% of people with IA in England prescribed a gabapentinoid in 2020 (3) - our findings support the role of existing safer gabapentinoid prescribing initiatives, particularly in people with IA.

Citation

Scott, I., Daud, N., Bailey, J., Twohig, H., Hider, S., Mallen, C., …Muller, S. (2024). AB0228 GABAPENTINOID USE AND THE RISK OF FRACTURES IN PEOPLE WITH INFLAMMATORY ARTHRITIS: NESTED CASE-CONTROL STUDY IN THE CLINICAL PRACTICE RESEARCH DATALINK (CPRD) AURUM. Annals of the Rheumatic Diseases, 83(Issue Suppl 1), 1352-1353. https://doi.org/10.1136/annrheumdis-2024-eular.4000

• Journal Article Type: Meeting Abstract
• Conference Name: EULAR 2024 European Congress of Rheumatology, 12-15 June. Vienna, Austria
• Conference Location: Vienna
• Acceptance Date: Jun 10, 2024
• Online Publication Date: Jan 2, 2025
• Publication Date: 2024-06
• Deposit Date: Sep 10, 2024
• Journal: Annals of the Rheumatic Diseases
• Print ISSN: 0003-4967
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 83
• Issue: Issue Suppl 1
• Pages: 1352-1353
• DOI: https://doi.org/10.1136/annrheumdis-2024-eular.4000
• Public URL: https://keele-repository.worktribe.com/output/919150
• Publisher URL: https://ard.bmj.com/content/83/Suppl_1/1352.2