Inflammatory arthritis Musculoskeletal Diseases
Conditions
Interventions
This trial will compare the effect of a 48-week daily dose of Baricitinib (Arm A) vs. standard care (Arm B) in a population of individuals at moderate to high risk of developing inflammatory arthritis
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Musculoskeletal symptoms and have tested positive for anti-CCP antibodies (CCP2 test) 2. Aged >18 years 3. Are able to read, understand, and give written informed consent 4. Consents to be randomised to either Baricitinib treatment or continued usual care 5. At moderate to high risk of progression to IA as calculated using a prediction model to risk stratify individuals based on the following predictors: 5.1. Tenderness of =1 small joint of the hands or feet defined by the physician (1 point) 5.2. Early morning stiffness duration =30 min (1 point) 5.3. RF and/or anti-CCP Ab concentration >3x upper limit of normal. (2 points) Those with a score of =3 will be eligible to participate.
Exclusion criteria
Exclusion criteria: 1. Previous diagnosis of RA or other form of inflammatory arthritis including, but not limited to SLE, psoriatic arthritis, ankylosing spondylitis, gout or pyrophosphate arthropathy and including current treatment with DMARDs or biological therapy, or a history of DMARD or biological therapy that in the opinion of the investigator constitutes a therapeutic dose 2. Clinical synovitis on clinical examination by a rheumatologist 3. Palindromic rheumatism 4. Individuals who are largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair 5. Presence of concomitant illness likely to require systemic steroid therapy during the study, in the opinion of the investigator 6. Co-morbidities requiring chronic treatment with immunosuppressive or immune modulating therapy 7. Treatment with an oral, intravenous, intramuscular, intrabursal or intraarticular corticosteroid within 12 weeks prior to randomization 8. Have had any major surgery within 12 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator, would pose an unacceptable risk to the screenee 9. Scheduled for or anticipating joint replacement surgery 10. History of acute allergic reactions to biologic therapies or immunoglobulins 11. Have experienced any of the following within 12 weeks of screening: myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure 12. Uncontrolled hypertension (=160/95 mmHg), uncontrolled diabetes, cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia, or any other cardiovascular condition in the past 24 weeks prior to Screening, which, in the opinion of the investigator, would put the screenee at risk by participating in the study 13. Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data 14. Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for 4 weeks prior to baseline. Screenees will be excluded if they are exposed to herpes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Proportion of individuals developing inflammatory arthritis (IA) measured according to clinical diagnosis at, or before, 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of participants developing IA measured according to clinical diagnosis at, or before, 96 weeks 2. Time to develop IA measured according to clinical status between baseline and 96 weeks 3. Joint tenderness measured using mean 53 tender joint count at 48 and 96 weeks 4. CRP levels measured using blood tests at 48 and 96 weeks 5. Physician assessment of disease activity measured using median physician assessment of global disease activity visual analogue scale (VAS) at 48 and 96 weeks 6. Early morning stiffness measured using median early morning stiffness duration at 48 and 96 weeks 7. Ultrasound synovitis measured using median total ultrasound synovitis (grey scale & power Doppler) and erosion scores at 48 and 96 weeks 8. Joint erosion and joint space narrowing measured using mean van der Heijde modified Sharp score at 48 and 96 weeks 9. Median participant-reported measures measured using the following at 48 and 96 weeks: 9.2. Functional impairment (Health Assessment Questionnaire Disability Index) 9.3. Quality of life index value and general health VAS (EQ-5D-3L) 9.4. Joint symptom VAS 9.5. Pain VAS 9.6. Fatigue VAS 9.7. Work Instability (Rheumatoid Arthritis Work Instability Scale) 10. Mean T cell subset levels measured using blood tests at 48 and 96 weeks | — |
Countries
United Kingdom
Contacts
Public ContactTim Hardy
Outcome results
None listed