None listed
Conditions
Brief summary
The aim is to assess at what timepoints any relevant MRI changes are seen with upadacitinib use; which aspects of rheumatoid involvement respond earliest; and if this precedes the timepoints when other clinical RA outcome measures change. Clinical response to treatment will involve assessing response to treatment on MRI of the participant’s most affected hand/wrist (as determined by Investigator assessment by examination at screening). This trial will observe improvements in MRI tenosynovitis, synovitis and osteitis, and evaluate the time to improvement/resolution of these MRI features, as well as clinical outcome measures such as inflammatory markers and joint count assessments. In addition, participant reported outcomes (PROs) will be completed to assess the overall disease activity levels as reported by the participant. The PROs chosen include the conventional PROs EQ-5D, SF-36, FACIT-F and PtGA as these are well-established PROs that have demonstrated validity and reliability in assessing disease state, as well as a specific upper limb function PRO, the DASH. The DASH, which was developed by the Institute for Work & Health4, specifically assesses hand function and is therefore relevant to the objectives of the study. This trial is novel in nature as it looks are earlier MRI timepoints than what has been completed in earlier clinical trials and also compares the MRI findings to PRO data captured at the same timepoint, which has also not been completed in earlier trials.
Interventions
Upadacitinib 15mg oral tablet, once per day for 24 weeks of treatment. No dose modifications will be made. Single-arm and open-label.
Compliance will be checked using compliance calculations throughout the trial at clinic visits.
Sponsors
Emeritus Research Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1 Male or female adult participants greater than or equal to 18years of age who can give informed consent, able to understand English and willing and able to complete the study activities and has been assessed by a Rheumatologist as suitable to commence upadacitinib as part of their rheumatoid arthritis management and will commence this treatment at baseline. 2 Clinically defined active rheumatoid arthritis despite methotrexate use (with or without other DMARDs), where active rheumatoid arthritis is defined as a DAS28-CRP greater than or equal to 3.2 at screening. 3 Clinically active synovitis (defined by synovitis sum score of greater than or equal to 3) of the chosen hand or wrist on MRI at screening, as determined by the MRI reader. 4 The methotrexate dose must be less than or equal to 25mg per week and the participant must also be on folic acid supplement according to local standard of care. The methotrexate dose must have been stable for greater than or equal to 3 months prior to baseline. 5 If the participant is on a DMARD in addition to methotrexate at the time of screening (allowed but not required), the dose must have been stable for greater than or equal to 3 months prior to baseline and remain stable throughout the duration of the trial. Note: the combination of leflunomide and methotrexate is allowed but with a cap of no more than 2 trial participants using this combination. 6 Non-steroidal anti-inflammatory drug (NSAID) medications are allowed but the participant is not required to be using these medications. If NSAIDs are being taken at the time of screening, the dose must have been stable for greater than or equal to 10 days prior to baseline and remain stable throughout the duration of the trial. 7 Prednisolone or equivalent is allowed but the participant is not required to be using this medication. If prednisolone (or equivalent) is being taken at the time of screening, the prednisolone dose must be less than or equal to10mg per day (or equivalent) and the dose must have been stable for greater than or equal to 2 weeks prior to baseline and remain stable throughout the duration of the trial.
Exclusion criteria
1. Negative MRI of the chosen hand/wrist (i.e. no signs of active clinical synovitis defined as synovitis sum wrist and MCP score less than 3) at screening as determined by the central MRI reader. 2. Inability to have MRI with gadolinium due to either claustrophobia or other contraindications to MRI with gadolinium. 3. Screening eGFR less than 60 mL/min/1.73m2 4. Any prior use of biologic treatment or targeted synthetic DMARD (JAK inhibitor). 5. Use of any intra-articular corticosteroid use in the previous 3 months in the chosen hand/wrist. 6. Any prior joint surgery in the chosen hand/wrist. 7. If the participant is a female of child-bearing potential: Currently pregnant or breastfeeding or plan to become pregnant or breastfeed during the course of the study. The participant must use contraception throughout treatment and for four weeks after the last dose. Females who are not of child-bearing potential (post-menopausal women, permanently sterile) are not required to use contraception. Same sex relationships are not required to use contraception. 8. Recent infection requiring intravenous antibiotics in the previous three months. 9. Any history of malignancy in the participant’s lifetime. Adequately treated squamous cell carcinoma, basal cell carcinoma and carcinoma in situ of the cervix are acceptable. 10. Live vaccines in the previous three months or plans to receive a live vaccine while on study (inactivated vaccines are acceptable). 11. Contraindication to use of upadacitinib. 12. Active Tuberculosis (TB) as determined by local QuantiFERON gold and local chest x-ray. If latent TB is diagnosed, the participant may be enrolled into the study providing treatment for latent TB according to local standard of care is initiated prior to the first dose of upadacitinib. If results are available from a chest x-ray and/or QuantiFERON gold within the three months prior to baseline, there is no need to repeat and these results can be used to assess eligibility. 13. Positive Hepatitis B, Hepatitis C or HIV laboratory tests. If results are available from Hepatitis B, Hepatitis C or HIV laboratory tests within the three months prior to baseline, there is no need to repeat and these results can be used to assess eligibility.
Outcome results
None listed