The Clinical and Cost-effectiveness of Oral Versus Intramuscular Glucocorticoids in Rheumatoid Arthritis: Protocol for a multicentre randomised controlled trial with economic evaluation and qualitative sub-study (LEADER trial)

Introduction Glucocorticoid (GC) bridging therapy is recommended in patients with rheumatoid arthritis commencing a disease-modifying anti-rheumatic drug (DMARD). It is not clear whether GC therapy is better administered intramuscularly (IM) or orally and at what dose level. The aim of the LEADER trial is to identify the most effective and safest way of using steroids in patients with uncontrolled RA who are starting a DMARD. Methods and Analysis A multi-centre, randomised, open-label, four-arm, parallel-group clinical trial with internal pilot phase, economic evaluation and qualitative study of acceptability. Participants will be randomised to one of four arms: arm A. 30mg oral prednisolone tapering over six weeks; arm B. 15mg oral prednisolone tapering over four weeks; arm C. IM 120mg methylprednisolone; arm D. IM 80mg methylprednisolone. Participants will be assessed at baseline (pre-GC intervention), 4, 12 and 24 weeks. The primary outcome measure is the mean DAS(CRP)-28 over 12 weeks. The primary comparison will be according to route of administration (Oral versus IM GC treatment) with secondary comparisons within route of administration to provide evidence of dose effectiveness. Toxicity will be measured using The Glucocorticoid Toxicity Index©, a clinical outcome assessment and early morning cortisol level. LEADER will be conducted in ~30 sites delivering NHS care, recruiting a sample size of 448. Economic evaluation will compare cost-effectiveness within-trial and over a lifetime horizon from the English National Health Service perspective.