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23/153 Janus kinase inhibitors for the treatment of juvenile idiopathic arthritis


Published: 30 November 2023

Version: 1.0 November 2023

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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 is the clinical and cost-effectiveness of Janus kinase inhibitors versus anti-tumour necrosis factors drugs for the treatment of children and young people with active juvenile idiopathic arthritis?

  • Intervention: Tofacitinib (a Janus kinase inhibitor, applicants to define and justify dosage regimen).
  • Patient group: Children and young people aged 2-18 years who were diagnosed with juvenile idiopathic arthritis (JIA) before the age of 16 years, and currently have active JIA despite standard first-line treatment, and who had an inadequate response or intolerance to standard dose methotrexate (applicants to define and justify appropriate JIA subtypes, and treatment regimens).
    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:  Paediatric rheumatology centres.
  • Comparator: Adalimumab (an anti-tumour necrosis factor drug, applicants to define and justify dosage regimen).
  • 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.
  • Important outcomes: Juvenile Arthritis Disease Activity (JADAS) minimal disease activity score (<3.8), and quality of life.
    Other outcomes: JADAS inactive disease score (<1) at 6 months; change from baseline in JADAS-27 at 3, 6 and 12 months; patient and parent/carer acceptability; participation in activities of daily living; frequency of arthritis flares and requirement for additional treatments, including corticosteroids and disease-modifying antirheumatic drugs (DMARDs); adverse events; cost-effectiveness.
    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).
  • Minimum duration of follow-up: 12 months.
    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.


Juvenile idiopathic arthritis (JIA) is a term for a group of syndromes in which the onset of inflammatory arthritis occurs before the age of 16 years and lasts longer than six weeks. It is relatively rare, affecting approximately 10,000 children in the UK.

Symptoms of JIA include joint pain or stiffness, swollen joints, fatigue, and problems with eyesight. These symptoms can negatively impact on a child’s ability to participate in family, school and leisure activities, affecting the quality of life of the child and that of their family. If the inflammation is not treated successfully it can lead to cartilage and bone damage, and the risk of permanent disability.

With JIA it is important to relieve the inflammation as soon as possible, in order to try and reduce long term damage. Methotrexate, a disease-modifying antirheumatic drug (DMARD) is used to try to induce remission from active disease if the first line treatment of corticosteroids is ineffective, or if the JIA is severe or affecting major joints such as the spine and hips. However, methotrexate does not work for everyone, and some children may be unable to tolerate it. These children will need to start biologic treatment with the anti-tumour necrosis factor drug adalimumab which is given via injection. If adalimumab is not effective, or not suitable, current guidelines recommend tofacitinib, a Janus kinase inhibitor, which is in the form of a tablet.

It has been proposed that tofacitinib could be offered before starting biologic treatment, without trying adalimumab first. This would provide an oral treatment option which may be preferable to both children and their parents/carers. As such, the NIHR Clinical Research Network - Children and Young People identified this uncertainty as one of their key priorities, highlighting the need for a randomised controlled trial. Applicants should consider features to minimise the risk of bias in proposed outcomes.

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

Making an application

If you would like to apply for this call, you can begin your application via the funding opportunity page.

Your application must be submitted online no later than 1pm on 28 March 2024. Applications will be considered by the HTA Funding Committee at its meeting in May 2024.

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

Shortlisted Stage 1 applicants will be given 8 weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in September 2024.

For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team, other than in unusual circumstances (for example, a lead from a named charity or a unique national expert in a condition).

For such exceptions, each application needs to state the case as to why the same person is included. The shared co-applicant should not divulge application details between teams, and both teams should acknowledge in their application that they are aware of the situation, and that study details have not been shared.

Should you have any queries please contact