”When drug development has reached a level of approval, this oral treatment might be an attractive and affordable choice to treat RA patients in developing countries.”—Raphaela Goldbach-Mansky, MD
Dr. Golbach-Mansky told Musculoskeletal Report, “This treatment is used in China for patients with rheumatoid arthritis. I am not aware of any other countries where the extract is currently used. When drug development has reached a level of approval, this oral treatment might be an attractive and affordable choice to treat RA patients in developing countries.”Researchers from 2 US academic centers and 9 rheumatology subspecialty clinics randomized 121 patients who had active RA and 6 or more painful and swollen joints. Patients received either sulfasalazine, 1g twice daily, or an extract of Tripterygium wilfordii Hook F (TwHF, also known as thunder god vine or lei gong teng), 60mg three times daily. All patients stopped disease-modifying antirheumatic drugs (DMARDs) at least 28 days before randomization, but they could continue stable doses of oral prednisone or NSAIDs.
Thunder god speaks: high efficacy, low toxicity
The primary outcome was the rate of achieving 20% improvement in the American College of Rheumatology criteria (ACR20) at 24 weeks.
Half of the patients dropped out, and this paper reports outcome data for 62 patients at 24 weeks (37 on TwHF, 25 on sulfasalazine. Over twice as many patients discontinued sulfasalazine for adverse events as discontinued TwHF for adverse events (17 vs. 7, P=0.039). Thirteen in the sulfasalazine and 5 in the TwHF group discontinued due to lack of efficacy.
A mixed-model analysis that imputed data for dropouts showed ACR20 responses in 65.0% of TwHF patients vs. 32.8% of sulfasalazine patients (P=0.001). TwHF also produced more ACR50 and ACR70 responses.
“Significant improvement was demonstrated in all individual components of the ACR response, including the Health Assessment Questionnaire disability score. Interleukin-6 levels rapidly and significantly decreased in the TwHF group. Although not statistically significant, radiographic progression was lower in the TwHF group,” the authors write.
Dr. Raphaela Goldbach-Mansky, who is in the Translational Autoinflammatory Disease Section at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, MD, said that adverse effects were similar with the two treatments. She also said that the researchers were surprised at some of the rapid responses seen.
Translating research into practice: TwHF—Don't try this at home
TwHF was initially studied by researchers as a potential male contraceptive. Parts of the plant are widely available, and MSKreport.com found that the Internet provides numerous recipes for home-brewed extracts of this herb.
That raised red-flag safety issues for Dr. Goldbach-Mansky. “This herb has a lot of toxicities if not prepared correctly and in a standardized fashion, she said. No standardized preparation is currently available in the US, and nonstandardized preparations have been associated with liver toxicity.
“The peeled roots have less toxicity than the non-peeled roots, and some of the side effects are associated with the compounds in the extract that are not active in suppressing the inflammation,” Dr. Goldbach-Mansky said.
She added, “Our study points to a potential new therapeutic option for patients with RA, but patients with RA should not obtain drug offered on the Internet. These preparations are not standardized for triptolide and tripdiolides, the active components used to standardize the drug in our study. Therefore the toxicity of the preparations available over the internet may be worse than what we have seen in our study.”
Dr. Goldbach-Mansky said that additional studies are planned.
“Dr. Peter Lipsky, who has retired from the NIH and is currently the Chair of the Phytomedics Scientific Advisory Board, will continue with the further product development. He is involved in developing a follow up trial with the goal of obtaining FDA approval,” Dr. Goldbach-Mansky said. Dr. Lipsky was senior author on this paper.
Phytomedics, which provided funds for making the standardized extract and testing it for toxins and adulterants, is commercially developing the drug as PMI-001. According to the company, “PMI-001 exerts its potent anti-inflammatory/immunosuppressant activities through unique and synergistic modes of action including inhibition of IL-2, a-TNF, i-NOS, and COX-2 gene transcription.”
Reference
1. Goldbach-Mansky R, Wilson M, Fleischmann R, et al. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis. A randomized trial. Ann Intern Med. 2009;151:229-240.
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