Phase II proof of concept study of baricitinib in individuals who are considered at risk of developing inflammatory arthritis: ExIST

INTERVENTION: 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 (IA). Participants in Arm A will be given a 2 mg daily oral dose of Baricitinib for 48 weeks. Participants in Arm B will undergo standard care, which is follow‐up without treatment. Participants will be randomised 1:1 to Arm A and Arm B by the Medicines Management and Pharmacy Services team at Leeds General Infirmary using a randomisation list. CONDITION: Inflammatory arthritis ; Musculoskeletal Diseases PRIMARY OUTCOME: 1. Proportion of individuals developing inflammatory arthritis (IA) measured according to clinical diagnosis at, or before, 48 weeks SECONDARY OUTCOME: ; 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 inde Xvalue 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; 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 >3 Xupper limit of normal. (2 points) Those with a score of =3 will be eligible to participate.