**4. Benefit of tripterygium wilffordii hook F in patients with rheumatoid arthritis**

#### **4.1 Tripterygium wilffordii hook F therapeutics**

In traditional Chinese medicine, extracts of the roots of Tripterygium Wilffordii Hook F (TwHF, *Lei Gong Teng*) has been widely used for the treatment of autoimmune and inflammatory disease in China. Several clinical trials have examined the therapeutic effects of TwHF in patients with rheumatoid arthritis (Cibere et al., 2003; Goldbach-Mansky et al., 2009; Tao et al., 2001; Tao et al., 2002; Vitetta et al., 2008). In an early nonrandomized controlled clinical trial, Tao and colleagues evaluated 13 patients with established rheumatoid arthritis who received a maximum dosage of 180 mg/day of TwHF. There were no adverse effects or disease improvements observed at that dosage and nine patients tolerated the extract up to a dosage of 570 mg/day. Eight of the nine patients who received the extract at doses over 360 mg/day experienced improvement in both clinical manifestations and laboratory findings and one patient met American College of Rheumatology criteria for remission (Tao et al., 2001). The results of this small trial suggested that the ethyl acetate extract of the Chinese herbal remedy was safe with tolerable side effects for most patients with rheumatoid arthritis who achieved clinical benefits. Subsequently, the same group of investigators used a prospective, double-blind, placebo-controlled trial for another 35 patients and found that eight patients in the 20-week low-dose (180 mg/day) group and four patients in the high-dose (360 mg/day) group met criteria for clinical response. The authors also concluded that the ethanol/ethyl acetate extract of TwHF, at a dosage of 360 mg/day, appeared to be safe in patients with rheumatoid arthritis (Tao et al., 2002). Another Chinese randomized double-blind placebocontrolled trial of 61 patients with rheumatoid arthritis suggested that six weeks of TwHF significantly improves American College of Rheumatology 20% response rate compared with placebo (TwHF 58% vs placebo 20%; P=0.002) (Cibere et al., 2003).

Recently, to compare the benefits and side effects of TwHF extract with those of sulfasalazine, a large randomized, controlled trial of 121 patients with active rheumatoid arthritis used TwHF extract 60mg, three times daily or sulfasalazine 1g, twice daily. Patients could continue stable doses of oral prednisone and non-steroidal anti-inflammatory drugs but not disease-modifying antirheumatic drugs. Among patients who continued treatment for 24 weeks, achievement of 20% improvement in American College of Rheumatology criteria was greater with TwHF than with sulfasalazine. Adverse event rates were similar. Also, patients receiving TwHF had significantly higher response rates for American College of Rheumatology 50% and American College of Rheumatology 70% criteria. In the TwHF group, significant improvement was demonstrated in all individual components of the American College of Rheumatology response, including the Health Assessment Questionnaire score. Interleukin-6 levels rapidly and significantly decreased in the TwHF group (Goldbach-Mansky et al., 2009).

The long-term effects and toxicities of TwHF and the potential combination of TwHF with other antirheumatic therapies need to be further investigated. However, evidence demonstrates that treatment with a standardized extract from the peeled roots of the Chinese herbal remedy TwHF administered from four weeks to over 24 weeks may be both effective and safe in treating patients with active rheumatoid arthritis.
