Polymyalgia rheumatica (PMR) Musculoskeletal Diseases
Conditions
Interventions
The NIHR Health Technology Assessment Programme has a long-standing collaboration with the Australian National Health Medical Research Council (NHMRC) inviting collaborative international research pro
Sponsors
University of Leeds
University of Adelaide
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Consent to participate (written, informed consent or witnessed verbal informed consent) 2. ALL of: 2.1. Documented diagnosis of PMR, confirmed by the local investigator 2.2. Previous steroid-responsive bilateral ache in the region of the trapezius, shoulder or upper arms, as reported by the patient to the secondary care site research team 2.3. Previous C-reactive protein (CRP) greater than 5 mg/L, or erythrocyte sedimentation rate (ESR)/plasma viscosity above local laboratory reference range, at either diagnosis or at time of a flare of PMR 3. At least 4 points from a possible 6: 3.1. Previous stiffness in association with other features of PMR, as reported by the patient to the secondary care site research team: 2 points 3.2. Previous aching of hip area (groin, buttock, lateral hip or upper thigh) in association with other features of PMR, as reported by the patient to the secondary care site research team: 1 point 3.3. Rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA/anti-CCP) both within local laboratory reference range at or during the 1 year prior to the screening visit: 2 points 3.4. No rheumatologist-documented hand or foot synovitis during active PMR symptoms: 1 point 4. Currently taking steroid treatment for PMR and willing to attempt dose reduction (tapering), as reported by the patient to the secondary care site research team 5. At least one previous relapse during steroid therapy, defined as steroid-responsive recurrence of PMR symptoms (aching in hip and/or shoulder areas), as reported by the patient to the secondary care site research team 6. Age 18 years or more at the time the consent form is signed Footnote 1: Acceptable documentation may include but not be limited to referral documentation from the GP practice, GP records containing diagnostic code (e.g. Read code, SNOMED code), or letter from an appropriately trained and qualified physician documenting the diagnosis
Exclusion criteria
Exclusion criteria: 1. Contraindication to tapering steroid dose, or to methotrexate therapy 2. Women who are currently pregnant or lactating or planning to become pregnant in the next 2 years 3. Women of child-bearing potential (WCBP) or men unwilling to use an effective birth control measure (Appendix 2) whilst receiving treatment (either methotrexate or leflunomide) and for an appropriate period after the last dose of protocol treatment (6 months in the case of methotrexate, applicable for both male participants and women of childbearing potential [WCBP]). In the case of male participants the contraceptive measures can be taken by either themselves or their female partners 4. A medical condition other than PMR that has required >2 courses of systemic glucocorticoid treatment lasting 5 days or more, or any course lasting 30 days or more, during the year prior to randomization 5. Giant cell arteritis (previous or current) 6. Rheumatoid arthritis, psoriatic arthritis or spondyloarthritis (previous or current) 7. At the baseline visit active infection of sufficient severity to be a contra-indication to commencing methotrexate 8. Treatment with trimethoprim or trimethoprim-sulfamethoxazole (co-trimoxazole) at the time of the baseline assessments 9. Active gastric ulcer at the baseline visit 10. Known prior history of a significant immunodeficiency syndrome, defined as an immunodeficiency severe enough to cause recurrent infections of sufficient frequency or severity to preclude DMARD treatment 11. Known prior history of hereditary galactose intolerance, hereditary total lactase deficiency or hereditary disorder of glucose-galactose malabsorption 12. Other medical condition that is severe enough to seriously compromise evaluation of the primary or key secondary endpoints 13. Treatment with any immunosuppressive therapy (conventional synthetic, targeted synthetic or biological DMARD) within 3 months prior to randomisation 14. Treatment with any investigational drug in the last 4 months prior to the start of protocol treatment 15. Unable to complete essential study procedures and communicate with study staff independently 16. Participants must NOT fulfil any of the following within 6 weeks prior to baseline: Haemoglobin 2 x upper limit of reference range for the laboratory conducting the test, eGFR (estimated glomerular filtration rate) <30 ml/min 17. Evidence of respiratory disease on chest radiograph (performed during screening or within the 6 months prior to screening) of sufficient severity to be a contra-indication to commencing methotrexate Footnote 2: Contraindication to MTX includes comorbidities such as severe respiratory disease or chronic infections.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean participant-reported cumulative prednisolone dose between randomisation and 18 months post-randomisation, reported by participants via a monthly questionnaire. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PMR symptom severity measured using the PMR-Impact Scale at weeks 0, 12, 24, 36, 48, 60, 72, 80 post-randomisation 2. Health-related quality of life measured using mean EQ-5D-5L Utility at weeks 0, 12, 24, 36, 48, 60, 72, 80 post-randomisation 3. PMR disease activity measured using mean PMR Activity Score (PMR-AS) at weeks 0, 24 and 80 post-randomisation 4. Time to steroid cessation evaluated at 18 months (can occur at any point). Time to steroid cessation, will be defined as the duration between date of randomisation and date at which participants report a current steroid dose of zero and there is sustained discontinuation of all steroids. Sustained discontinuation of steroids will be defined as not taking any further steroids for the duration of follow-up. The data to assess this will be collected via participants completing a ‘Steroid Use Questionnaire’ every four weeks, documenting their steroid doses over each of the preceding four weeks. 5. Time to steroid-free remission evaluated at 18 months (can occur at any point). Where participants report a current oral steroid dose of zero a decision as to whether or not steroid-free remission is achieved will be agreed between the participant and physician at the week 80 assessment. The steroid-dose of zero will be collected via participants completing a ‘Steroid Use Questionnaire’ every four weeks, documenting their steroid doses over each of the preceding four weeks. 6. Time to PMR relapse evaluated at 18 months (can occur at any point). Time to PMR relapse will be defined as the duration between randomisation and date of first PMR relapse. PMR relapse, which will be participant reported, will be defined as an increase in PMR symptoms sufficiently severe to require alteration of the steroid dosing plan. Participants will be asked every month via the Steroid Use Questionnaire whether they have had to adjust their planned steroid dosing plan due to an increase in PMR symptoms (patient reported relapse). 7. Number o | — |
Countries
Australia, England, United Kingdom, Wales
Outcome results
None listed