Open trial of thalidomide in the treatment of rheumatoid arthritis

Reports on the use of thalidomide in the last 20 years have described favorable responses in a variety of inflammatory conditions. We have performed an open trial to begin to assess further its efficacy in rheumatoid arthritis (RA). During a 3-year-period, 31 patients with chronic active RA were enrolled into a 4-month open trial using thalidomide, to assess its efficacy and safety. Of these patients, 21 began the study taking 300 mg/day and the other 10 patients began at lesser doses that were increased gradually. Patients were evaluated at least 7 times during the 4-month study. Of the 31 patients, 17 (55%) withdrew from the study over the course of 12 weeks because of adverse events and no benefit was seen in any of these patients with a mean dose of 177 mg/day. There were 14 patients taking thalidomide for 4 months, and 4 of the 14 (29%) responded to therapy, satisfying at least 4 of the 6 Paulus criteria; 6 of 14 (43%) partially responded to therapy, satisfying 3 of the 6 Paulus criteria; and 4 of 14 (29%) did not respond, with each group taking average dosages, respectively, of 304 mg/day, 264 mg/day, and 303 mg/day. Of the 14 patients completing the 4-month study, 9 patients consented to participate in an extended trial of thalidomide treatment for at least 4 more months. Patients showing partial benefit within the first 4 months are more likely to show definite benefit later on.This study did not confirm the level of effect previously reported with thalidomide. However, some patients with previously refractory RA did improve. Although we had no comparison group, we believe that, as an investigational therapy, thalidomide should be considered in patients with RA for whom other conventional treatment approaches have failed. Thalidomide should be administered initially at 50 mg/hs for 1-2 weeks and then increased by 50 mg every 1-2 weeks as tolerated. The major obstacle to short term use of thalidomide is drowsiness and the major adverse effect to long term use is peripheral neuropathy.