This study was conducted between March 2004 and October 2005 at 11 US centers in 121 patients with established (at least 6 months) active rheumatoid arthritis per the criteria of the American College of Rheumatology (ACR). Any patient taking a disease-modifying antirheumatic drug was required to discontinue use for 28 days before beginning the study, though nonsteroidal anti-inflammatory drugs (or oral prednisone taken by 17 patients in each treatment group) were allowed to continue at stable doses. Eligible patients were randomly assigned to receive either 60 mg of tripterygium extract 3 times daily for a total daily dose of 180 mg (Phytomedics; Jamesburg, New Jersey) (n = 60; age: 54 ± 11 years) or 1 g sulfasalazine twice daily for a total daily dose of 2 g/d (n = 61; age: 52 ± 12 years) for 24 weeks. Blood samples were collected at baseline, 2 weeks, and every 4 weeks for 24 weeks for the measurement of the erythrocyte sedimentation rate (ESR) and C-reactive protein, and at baseline, 4 weeks, and 24 weeks for interleukin-6, cholesterol panel, cortisol, adrenocorticotropic hormone, and rheumatoid factor concentrations. Radiographs of the hands and feet were obtained at baseline and at 24 weeks. Body weight and blood pressure were also measured. The primary outcome measure was a 20% or greater improvement (ACR 20 response) in tender and swollen joints and in 3 or more of the following: physician's or patient's assessment of global health status, patient's assessment of pain on a visual analogue scale, patient's assessment of function, and serum C-reactive protein concentration. Secondary outcome measures included the efficacy of tripterygium in achieving 50% (ACR 50 response) and 70% (ACR 70 response) improvements in the abovementioned outcomes at 24 weeks, improvement in the European League Against Rheumatism Disease Activity Score 28 (DAS 28), and radiographic scores of the hands and feet. The subjects were instructed to record any adverse events experienced, which were graded by severity.

Only 62 subjects (37 tripterygium, 25 sulfasalazine) completed the 24-week study. Significantly more of the sulfasalazine subjects withdrew due to lack of efficacy or adverse effects (P < 0.001). Approximately 68% of the tripterygium group and 36% of the sulfasalazine group who completed the study achieved an ACR 20 response (P = 0.02). Similarly, approximately 54% of the tripterygium group and 4% of the sulfasalazine group achieved an ACR 50 response, and approximately 38% of the tripterygium group and 4% of the sulfasalazine group achieved an ACR 70 response at 24 weeks (P < 0.001 and P = 0.002, respectively). The mean improvement in the DAS 28 score was 2.4 points in the tripterygium group and 1.5 points in the sulfasalazine group (P < 0.001). Significantly greater improvements in disability, pain, patient's and physician's global assessments of health, ESR, and C-reactive protein concentrations were observed in the tripterygium group than in the sulfasalazine group beginning at 2 weeks. A significantly greater improvement in the number of swollen and tender joints was observed in the tripterygium group than in the sulfasalazine group beginning at 8 weeks.

Radiographic scores indicated no progression in mean joint space narrowing or erosion in the tripterygium group. Compared with the sulfasalazine group, significantly greater decreases in interleukin-6 were observed at 24 weeks (P = 0.037) in the tripterygium group and in rheumatoid factor at 4 weeks in the tripterygium group (P < 0.001). Blood pressure, body weight, and cortisol and adrenocorticotropic hormone concentrations did not change significantly with treatment. Of note, total cholesterol concentrations increased significantly in the tripterygium group (P < 0.001); high-density-lipoprotein cholesterol increased by 53% and low-density-lipoprotein concentrations by 48%, but the ratio remained unchanged. The frequency of adverse events reported related to the drugs was not significantly different between groups (tripterygium 57% and sulfasalazine 61% of patients in the groups).

The authors conclude that "treatment with a standardized extract from the peeled roots of the Chinese herbal remedy [tripterygium] administered over 24 weeks may be both effective and safe in treating patients with active rheumatoid arthritis. The rapid improvement in function and pain and the profound effect on inflammation may make this extract an attractive and affordable alternative to currently available agents." Further studies need to evaluate the impact on cholesterol levels, long-term effects and toxicities, and combination with other antirheumatic therapies.