Title: PERISCOPE: PERIoperative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations
Funder: Department of Health and Social Care

Abstract: Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are common forms of inflammatory arthritis. They are caused by an overactive immune system and are treated with medicines that reduce pain and inflammation. In recent years, special immune-suppressing medicines, called biologics, have been developed, which are very effective in controlling the arthritis disease process and symptoms but can increase the risk of some infections. _x000D_ _x000D_ People with inflammatory arthritis often need orthopaedic surgery (e.g. joint replacement) to relieve pain and improve function due to the damage caused by arthritis. The potential for increased risk for surgical site infections is a particular concern for patients undergoing orthopaedic surgery as these can be associated with long-term pain and need for further surgery. Currently, biologics are usually stopped before any planned operation to try and reduce the risk of infection and other complications such as slow wound healing. However, stopping biologics increases the risk of the painful and debilitating flares and delay recovery from surgery. Flares are often treated with steroids, which can increase the infection risk and delay wound healing. There are no randomised trials to support current guidance of stopping biologics before surgery. _x000D_ _x000D_ We have designed this study proposal together with our Patient Advisory Group, which includes several people with arthritis treated with biologics and experience of orthopaedic surgery. We conducted a national survey of rheumatologists and surgeons and reviewed related previous research. All agreed that this important area needs further research._x000D_ _x000D_ We propose a study involving 394 people with inflammatory arthritis on biologics from several centres across the UK who require orthopaedic surgery. Participants will be randomly allocated to either stopping or continuing their biologics before undergoing orthopaedic surgery. For those that stop, we will follow the current national guidelines. Based on our Patient Advisory Group input and survey findings, we decided to include all types of orthopaedic surgery, from minor operations to major joint replacements. _x000D_ _x000D_ Following the advice from our Patient Advisory Group, we will conduct regular patient assessments for the first 12 weeks following surgery. This will give a complete picture during the recovery period after the operation. Patients stressed the importance of using a broad measure of health, rather than just focussing on pain or disease activity. So we are using PROMIS-29; a quality of life questionnaire as the main study outcome. We will also ask patients about their health and wellbeing periodically over the next 12 months. We will record complications (infections, flares), disease activity, medications, how often people seek care and who with. We will compare costs and interview participants and clinicians to understand their views and experiences. _x000D_ _x000D_ We will share our work with policymakers, national societies and publish it in journals. We will use social media platforms to make sure the results are visible to a large audience. With the Patient Advisory Group, we will develop patient information leaflets to explain the study results and act as a decision aid for future patients undergoing orthopaedic surgery. The findings will guide patients, carers, policy makers and clinicians on whether to stop or continue biologics when people with inflammatory arthritis undergo orthopaedic surgery.

Lay abstract: Research Question: What are the benefits and harms of continuation versus stoppage of biologics in patients with inflammatory arthritis (IA) undergoing orthopaedic surgery?_x000D_ _x000D_ Background: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionised the treatment of IA. However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to a risk of flares and loss of disease control. This issue has not been explored in an RCT._x000D_ _x000D_ Aims/Objectives: To determine the clinical effectiveness, cost effectiveness and acceptability of continuation versus stoppage of bDMARDs in patients with IA undergoing planned orthopaedic surgery._x000D_ _x000D_ Methods: We will conduct a multi-centre, superiority RCT with an internal pilot and nested qualitative study. This pragmatic study will be conducted across 20 NHS sites and include diverse populations. It will include adults with Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis and Juvenile Inflammatory Arthritis who are currently prescribed bDMARDs. 394 patients will be randomised 1:1, stratified by site, disease, surgery (soft tissue/metalwork/joint replacement) and sex. Patients will be followed for the first 12 months post-surgery. The primary outcome will be PROMIS-29 during the first 12 weeks after surgery. Secondary outcomes include assessment of physical function, disease activity, medications use (steroids, antibiotics, additional drugs), health care resource use and costs. Adverse events and patient satisfaction will be recorded. The primary and secondary outcomes will be compared using a covariance pattern mixed-effect linear regression model, incorporating post-randomisation time points. Delayed wound healing and surgical site infections will be compared using a generalised linear model; risk differences and relative risk will be reported. Cost-effectiveness will be evaluated using a within-trial cost-utility analysis from NHS and personal social services perspectives over 12 months. We will interview 30 patients and 20 clinicians to establish acceptability and experience of the potential trade-off between infection risk and disease control. We will explore ways in which information relating to risks and benefits could best be described in a clinical setting. This research has been co-produced at all stages by our PPI advisory group (PAG), including members from underserved populations. _x000D_ _x000D_ Timelines: An embedded pilot phase (9 months) will enable assessment of the recruitment strategy. The study will take 52 months in total._x000D_ _x000D_ Dissemination: The qualitative study will inform how the evidence should be described to key stakeholders to facilitate patient and clinician decision making as part of high-quality patient-centred care. With the PAG, we will co-develop a patient information sheet and decision aid to inform future patients and explain the risks/benefits in an accessible pictorial format. We will publish our findings in high-impact journals, which will be used to develop national and international guidelines. We will present at professional society events and organise press releases through NHS organisations. We will engage with rheumatology/orthopaedic communities, patient advocacy groups and charities in all disease areas to ensure broad adoption and implementation of the research findings

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM