A comparison of short-term efficacy and toxicity of 2 glucocorticoid bridging strategies in 2 clinical trials in early rheumatoid and undifferentiated arthritis

Objectives: To compare short-term outcomes of initial methotrexate therapy with higher or lower-dose glucocorticoid (GC) bridging in patients with early rheumatoid or undifferentiated arthritis. Methods: We compared two trials: a 'higher-dose GC'-study starting with methotrexate and 60 mg/day prednisone, tapered in 7 weeks to 7.5 mg/day (IMPROVED trial) and a 'lower-dose GC'-study, starting with methotrexate and prednisone 15 mg/day tapered in 10 weeks to nil (arm C of the tREACH trial). After multiple imputation, we compared the DAS and HAQ, rates of DAS-remission (DAS<1.6) and low disease activity (DAS <= 2.4) at the first follow-up visit after 3 to 4 months with linear and logistic regression models, adjusted for baseline DAS/HAQ, age, gender, symptom duration, ACPA positivity, BMI and damage. Results: Baseline symptom duration, DAS and HAQ were comparable, but more patients in the lower-dose GC-study arm C fulfilled the 2010 criteria for RA. After correction for confounders, patients in the lower-dose GC-study arm C had a significantly higher DAS (0.62 higher (95 % CI 0.43; 0.80) and HAQ (0.28 higher (95 % CI 0.17; 0.39) at the first follow-up visit compared to patients in the higher-dose GC-study, and less often DAS-remission (63.4 % versus 28.9 %) and low disease activity (80.6 % versus 55.7 %). Fewer adverse events were reported in the higher-dose GC-study. Conclusion: In patients with early RA or UA, a study with higher dosed glucocorticoids as part of initial treatment was associated with significantly better early clinical outcomes compared to a study with lower dosed glucocorticoids, and fewer early side effects. These results should be interpreted with caution due to risk of bias when comparing two distinct clinical trials instead of performing one trial.