Rheumatoid Arthritis - Other Agents

Clifton Bingham, M.D.

484 (Poster). A Multi-center, Double Blind, Randomized Study In Patients With Active Rheumatoid Arthritis (RA) Comparing An Extract From A Chinese Vine, Tripterygium Wilfordii Hook F (TWHF), To Sulfasalazine

AUTHORS: RT Goldbach-Mansky, M Wilson, S Alli, TH Pham, A Kivitz, J Silverfield, P Kempf, N Olsen, R Fleischmann, X Tao, PE Lipsky.

BACKGROUND: There is growing interest in the effects of many “natural” compounds in the treatment of arthritis and autoimmune diseases.  Many herbal compounds, and extracts from natural products have been demonstrated to have clinical efficacy and have been used for the treatment of disease.   Extracts from the vine Tripterygium Wilfordii Hook F (TWHF) have been used in China to treat inflammatory conditions including inflammatory arthritis for many years. Two small studies have suggested efficacy in RA.  The active ingredient Triptolide has been shown to be an anti-inflammatory and immunosuppressive agent with activity against activated lymphocytes and that promotes tumor cell death and promotes synoviocyte apoptosis.

METHODS: This was a double blind randomized multicentered trial of 121 with active RA with a standardized extract of TWHF compared to sulfasalazine.  Patients received either 60 mg tid of TWHF normalized for the active component Triptolide or 2g of sulfasalazine in divided doses. Standard clinical and lab assessments were performed and ACR responses at 24 weeks were the primary outcome using an ITT analysis.

RESULTS: 62% of patients on TWHF and 41% on sulfasalazine completed the study with the main reasons for drop out were adverse events in 17 pts on sulfasalazine and 7 pts on TWHF and lack of efficacy in 11 pts on sulfasalazine and 6 pts on TWHF.

The response to TWHF was rapid with 45% on TWHF and 9.8% on sulfasalazine achieving an ACR 20 response at 2 weeks. 16 serious adverse events occurred in 10 pts, all unrelated or unlikely related to study drug, 4 of those pts received TWHF, 6 sulfasalazine. Adverse event (AE) rates were similar in both arms, gastrointestinal AEs were most common, with nausea occurring in 34% pts receiving sulfasalazine and diarrhea in 23% patients on TWHF.

CONCLUSION: A root extract from the Chinese vine, TWHF, was effective and safe in treating patients with active rheumatoid arthritis. This agent may be an effective and affordable alternative treatment option in patients with active RA.

EDITORIAL COMMENT:  This was a well conducted, NIH-sponsored study demonstrating efficacy that was impressive for this compound compared with SSZ.  This study demonstrates the importance of conducting active comparator studies, though one could criticize the choice of SSZ instead of a standard MTX comparator.  There is some concern that there were so many drop outs in the SSZ group potentially contributing to the poorer than expected efficacy for this drug.  Additional work is needed to better understand not only the efficacy of this compound, but importantly its safety in conjunction with other agents that may be used to treat RA.  The active ingredient is a potent immunosuppressive agent, that if used unknowingly in combination with other DMARDS, may result in untoward side effects.  Furthermore some studies have shown affects on spermatogenesis that needs to be further studied and understood if patients use this compound.  The demonstration of efficacy of this product however in a carefully conducted clinical trial, will likely lead to the increased use of the compound by individuals.  Physicians should be alert to this possibility and include this in their questions to patients in understanding potential drug-drug interactions.