22/155 Oral versus intramuscular glucocorticoids in Rheumatoid Arthritis commissioning brief

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

In patients with active Rheumatoid Arthritis starting, switching or escalating DMARDS/biologics, what is the clinical and cost-effectiveness of oral versus intramuscular glucocorticoids?

1. Intervention: Oral glucocorticoids. Applicants to define and justify drug(s) and dosing regimens. 
2. Patient group: Adults with active rheumatoid arthritis initiating/escalating/switching DMARD/biologic treatment.
   Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
3. Setting: Secondary care; Rheumatology clinics.
4. Comparator: Intramuscular glucocorticoids. Applicants to define and justify drug(s) and dosing regimens. 
5. Study design: A 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.
6. Important outcomes: Disease activity (DAS 28); Quality of life; Function (HAQ); Pain (VAS).
   Other outcomes: Adverse events; Side effects; Drug discontinuation (due to adverse event and/or inefficacy); Cost effectiveness; Patient acceptability; Duration on steroid treatment.
   Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex (and other demographic factors where relevant). 
7. Minimum duration of follow-up: 6 months; To include short term measurements (e.g. 2 weeks, 1 month and 3 months). Applicants to define and justify.
   Longer-term follow up: If appropriate, researchers should consider obtaining consent to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study. 

Rationale

Rheumatoid arthritis (RA) is a disease in which the body's immune system attacks its own healthy tissue. The attack happens mostly in the joints (especially in the hands and feet) and causes pain, swelling and stiffness in the joint. In the UK approximately 1% of the population are thought to have RA. RA is a life changing diagnosis and has significant effects on quality of life and physical function. Many people with RA have restricted mobility and difficulties with activities of daily living including a person’s ability to work.

There is currently no cure for RA and treatment aims to control symptoms, improve quality of life and to prevent or reduce damage to the joints that occurs during the disease. The main treatment for RA is to use disease-modifying anti-rheumatic drugs, also known as DMARDS. DMARDS target the immune system to try and treat the immune dysregulation. Unfortunately, DMARDS can take weeks or months to have an effect and do not provide immediate relief of RA symptoms. While a person is waiting for DMARDS to take effect, steroids knowns as glucocorticoids (GCs) are often given to provide a more rapid relief from pain and stiffness. This is known as a bridging treatment. Most people with RA receive GCs at or shortly after diagnosis.

GCs can be given as oral tablets (commonly prednisolone) or a single injection into the muscle (intramuscular (IM) injection, commonly methylprednisolone). Both oral and IM GCs are used although there is considerable variation in practice in terms of choice of approach, dose and duration. Depending on individual and/or departmental practices most rheumatology clinicians will use both drugs in their clinical practice. Both oral and IM GCs have shown to be effective, but their comparative effectiveness has never been compared in a large randomised controlled trial.

There are many concerns around the use of GCs due to side effects. Side effects include but are not limited to red flushing of the face, tiredness, mood swings, weight gain, increased risk for cardiovascular diseases, infections, eye problems osteoporosis and fractures. Oral therapy can sometimes continue for months increasing the risk of side effects. IM GC injection is also sometimes associated with problems in the skin around the injection site. Because of these side effects guidelines state that GCs should be used at the most effective dose for the shortest amount of time.

There is a lack of high quality evidence looking at whether oral or IM GCs are better in terms of symptom relief, disease progression and side effects. There is also no guidance for the most effective dosing regimen for either oral or IM GCs. Trials are therefore needed to determine the best way of giving GCs. This topic has been highlighted as a research priority by a member of the HTA Prioritisation Committee: Hospital Based Care and is also a NICE research recommendation. The HTA programme therefore wishes to commission the trial outlined above. 

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. 

Your application must be submitted on-line no later than 1pm on the 29 March 2023. Applications will be considered by the HTA Funding Committee at its meeting in May 2023.

Guidance notes and supporting information for HTA Programme applications are available.

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 September 2023.

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: htacommissioning@nihr.ac.uk