Immune Checkpoint Inhibitor-induced Inflammatory Arthritis (ICI-IA) Musculoskeletal Diseases
Conditions
Interventions
Patients will be randomised using an online tool to either:
Arm A: Standard of care. Reducing course of prednisolone with a starting dose of 20mg/day or 40mg/day decided prior to randomisation (by th
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Informed consent must be obtained prior to any trial related procedures being performed 2. Able to understand and comply with the requirements of the trial 3. Inflammatory arthritis with at least one clinically swollen joint at screening 4. Male and female participants aged =18 years 5. Patient treated with ICI (concurrent with or last dose within 12 weeks prior to onset of inflammatory arthritis) 6. Decision of two treating physicians, one of whom must have expertise in the management of inflammatory arthritis, that treatment with systemic glucocorticoids would be appropriate management for their inflammatory arthritis. Details of the physicians who have decided this will be documented in the source data.
Exclusion criteria
Exclusion criteria: 1. If currently using oral glucocorticoids, use must not exceed 2 weeks prior to baseline (except hydrocortisone for adrenal replacement where longer term use is allowed). 2. Pre-existing (prior to first use of ICI) inflammatory arthritis due to rheumatic autoimmune disease 3. The arthritis not considered, by the treating physician, to be ICI-IA 4. Active or latent TB (unless having fulfilled chemoprophylaxis management according to local guidelines), or other chronic infection considered a contraindication to anti-TNF 5. Positive test for HIV, HCV (evidenced by both positive anti-HCV antibody and HCV-RNA in serum), Hepatitis B Virus (HBV) as evidenced by positive hepatitis B surface antigen (HBsAg) or anti-hepatitis B core antibodies (HBcAb) (further information on hepatitis B eligibility in Section X) within last 6 months 6. History of demyelinating disorder 7. Hypersensitivity to the active substance or to any of the excipients in the Adalimumab preparation 8. Any medical, surgical or psychiatric condition that the investigator believes may jeopardise the participant, or the validity of the trial results, were they to participate in the trial 9. Moderate to severe heart failure (New York Heart Association III/IV) 10. Concurrent use of other biological immunosuppressive drugs or Janus kinase inhibitors. 11. Live vaccine received less than 4 weeks before first dose of trial drug 12. Any current severe infection 13. Known ocular herpes simplex
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Glucocorticoid-free arthritis remission rate at 24 weeks where a patient is classed as being in glucocorticoid-free arthritis remission if: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks and (ii) Absence of synovitis on clinical examination | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to remission defined as time from randomisation to first absence of synovitis on clinical examination at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 2. Arthritis remission measured as absence of synovitis at 24 and 48 weeks 3. Drug-free arthritis remission measured as absence of synovitis with no ICI-IA treatment in the previous 4 weeks at 48 weeks 4. 66/68 swollen and tender joint counts at Screening, Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 5. Patient arthritis disease activity global VAS (0-100) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 6. Physician arthritis disease activity global VAS (0-100) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 7. Fatigue VAS (0-100) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 8. Pain VAS (0-100) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 9. Cumulative exposure to glucocorticoids over 24 and 48 weeks 10. Cumulative exposure to anti-TNF (or other biological DMARD or targeted synthetic DMARD) over 24 and 48 weeks 11. Cumulative exposure to other conventional synthetic DMARD over 24 and 48 weeks 12. Cumulative exposure to ICI over 24 and 48 weeks 13. Adverse events related to arthritis interventions (Adverse reactions) using CTCAE version 5 at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 14. Serious adverse events using CTCAE version 5 at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 15. Other IrAEs (number of organs and toxicity level) using CTCAE version 5 at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 16. Functional status as assessed by HAQ-DI at Weeks 0, 12, 24, 48 17. Health-related quality of life as assessed by EQ-5D-5L at Weeks 0, 12, 24, 48 18. Well-being as assessed by ICECAP-A questionnaire at Weeks 0, 12, 24, 48 19. Investigator Assessed Cancer Status as complete response, partial response, stable disease, or disease progression at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 20. Cancer response at weeks 24 and 48 as defined by RECIST 1.1 21. Overall survival as time to death at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, | — |
Countries
England, United Kingdom
Contacts
Public ContactManpreet Wilkhu
Outcome results
None listed