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21/25 Use of biologic drugs around the time of orthopaedic surgery commissioning briefs

 

Contents

Introduction

The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.

Research question

What are the benefits and harms of continuing biologic drugs in patients with rheumatoid arthritis undergoing orthopaedic surgery?

  • Intervention: Continuation of biologics over the perioperative period, (applicants to define and justify). 
  • Patient group: Patients with rheumatoid arthritis who use biologic disease modifying drugs and are planning to undergo elective orthopaedic surgery (applicants to define the types of elective orthopaedic procedures). Applicants may wish to justify expanding the target population to include other conditions such as ankylosing spondylitis, psoriatic arthritis and psoriasis.
    Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
  • Setting: Secondary care (applicants to specify and justify). 
  • Comparator: Discontinuation of biologic drugs over the perioperative period (to be defined and justified).  
  • Study design: A pragmatic randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop/go criteria should be provided to inform progression from pilot to full trial. Applicants should clarify their approach to concomitant non-biologic disease-modifying antirheumatic drugs and to masking. 
  • Important outcomes: Disease activity; delayed healing; surgical site infection; health-related quality of life.
  • Other outcomes and outputs: Other adverse events; use of antibiotics; use of steroids or other non-biological agents for disease control; needing a new biologic; cost-effectiveness; patient and clinician experience and acceptability; risk-benefit analysis. Applicants may wish to consider subgroup analyses if appropriate.
    Where established Core Outcomes exist, they should be included amongst the list of outcomes unless there is good reason to do otherwise. 
  • Minimum duration of follow-up: 12 months.
  • Longer-term follow-up: If appropriate, researchers should consider obtaining consent from participants to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study, e.g. to investigate periprosthetic joint infection rates and other long-term effects in relation to medication regimens.

Rationale

Rheumatoid arthritis (RA) is an inflammatory disease that largely affects synovial joints, especially the small joints of the hands and feet. The condition is more common in women than it is in men. Most patients are diagnosed between the ages of 40 and 60, but people can develop the condition at any age. RA is associated with significant morbidity, including pain and disability. It is a systemic disease that can affect the whole body (e.g. heart, lungs, and eyes), and is not limited to the joints. In addition, people with rheumatoid arthritis are at increased risk of developing complications after surgery.

People with severe or hard to control RA may be prescribed 'biologic' disease-modifying drugs (also known as 'biologics'), which are often highly effective. These drugs have immunosuppressive properties that could further increase the risk of infection. Hence, there is concern that people with RA who undergo surgery, may be at increased risk of postoperative complications such as surgical site infection or delayed healing. Some guidelines, including a guideline developed by the British Society for Rheumatology, suggest biologics could be discontinued prior to elective (planned) surgery. However, withdrawal of biologics may result in increased risk of disease flares and a decline in disease control, which may require the biologic to be changed. Steroid therapy may be prescribed to control disease flares; however, these drugs could further increase the risk of infection. Some experts believe that this risk could be higher than in biologic therapies.

Current guidelines are based on expert consensus informed by very limited and contradictory evidence. Most published studies are retrospective analyses of routine clinical data, generally reporting surgical site infections and delayed healing. In contrast, postoperative disease flares associated with withdrawal of biologics are rarely considered in the literature.

To our knowledge, the research question has not been explored in randomised controlled trials, and the perioperative management of biologics remains an area of clinical uncertainty. The HTA programme wishes to fund a study as outlined above that will generate evidence to guide future clinical practice and to inform patient choice. Applications should demonstrate buy-in from both rheumatologists and orthopaedic surgeons, and from other relevant groups to provide a strong interdisciplinary team including PPI.

The programme acknowledges that in addition to rheumatoid arthritis, it is also unclear whether patients with ankylosing spondylitis, psoriatic arthritis, or psoriasis should pause biologic drugs around the time of orthopaedic surgery. Applicants who wish to include these or other additional patient groups in the proposed study should justify their decision and explain how multiple groups would be managed within the trial.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email htaresearchers@nihr.ac.uk.

Making an application

If you wish to submit a Stage 1 application for this call, the online application form can be found on the funding opportunities page. To select this call, use the filters on the right of the screen or search using the call name and/or number.

Your application must be submitted on-line no later than 1pm on the 28 July 2021. Applications will be considered by the HTA Funding Committee at its meeting in September 2021.

Guidance notes and supporting information for HTA Programme applications are available by clicking the links.

Important: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in January 2022.

Applications received electronically after 1300 hours on the due date will not be considered.

For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team. There may be unusual circumstances where the same person could be included on more than on application eg a lead from a named charity or a unique national expert in a condition.

For such exceptions (i) each application needs to state the case as to why the same person is included (ii) the shared co-applicant should not divulge application details between teams and (iii) both teams should acknowledge in their application that they are aware that one of their co-applicants is part of a competing application and that study details have not been shared.

Should you have any queries please contact us at htacommissioning@nihr.ac.uk.