MRI Evaluation Assessing Synovitis to Address the Unmet Need for Reliable Endpoints in SLE

This will be a six month, double blind, randomized, placebo- controlled trial of subcutaneous methotrexate vs methotrexate plus baseline Depomedrol in patients with SLE and \>/= 3 tender and 3 swollen joints in the hands and wrists. Patients who are already taking methotrexate \</= 15 mg/week may qualify and will have a \>/= 2.5 mg/week dose increase at baseline, receiving subcutaneous dosing whether on oral or sc dosing prior to entry. Those not taking methotrexate at baseline will initiate open label treatment in ascending doses beginning at 15 mg/week. All patients will increase methotrexate weekly up to 25 mg as tolerated or until resolution of arthritis. Decreases are allowed as needed. After randomization, patients may choose to stop or continue any NSAIDs, hydroxychloroquine, or up to 10 mg prednisone if these were being used at screening. All other lupus-specific treatments or medications will be withdrawn. Optimization of methotrexate dose must be completed by Month 2. If additional immune- suppressive medications or steroids become necessary during the trial, patients remain evaluable for the primary endpoint, which is defined by clinical response regardless of treatment. In secondary analyses of Depomedrol vs. placebo, patients treated with rescue interventions will be censored when comparing changes in mean/median synovitis, osteitis RAMRIS or tendinitis scores in the two treatment groups, and they will be included as non- responders in dichotomous endpoints (SRI-4, BICLA). These analyses will also provide useful data for many of the other endpoints (comparisons of MRI vs joint counts and other measures which are valid regardless of treatment). Thus, although off protocol medications will not be encouraged, they will not require removal from the study.