Sphaeranthus indicus: Traditional Wisdom to Modern Medicine—An Orally Active, Potent Cytokine Inhibitor for the Management of Inflammatory Disorders

This article is about the efficacy of Sphaeranthus Indicus extract for use as an immunomodulator for the treatment of inflammation in rheumatoid arthritis. Rheumatoid arthritis inflammation has successfully been treated with cytokine blockade agents such as anti-TNF-a and anti-IL-17 biologics which are immunomodulatory. Sphaeranthus Indicus is a plant extract that has immunomodulatory effects similar to certain biologics. The purpose of this study was to determine the effectiveness of Sphira (another name for the plant extract) of treating inflammation via anti-TNF activity and other inflammatory pathways intervention

The methods used to test Sphira were done in vitro and in vivo throughout several mediums including blood from healthy donors, synovial cells from RA patients and in mice. The primary results from the study confirms a variety of beneficial effects, including validating the use of Sphira to modulate the release of inflammatory cytokines This extended to T-cell mediated cytokines such as IL-17 as well as IL-12/IL-23. The extract was also shown to reduce the production of TNF-a  and IL-1B in mice, which are known to be utilized in inflammatory pathways. Another benefit of Sphira was modulation of cell adhesion molecules that produce inflammation such as ICAM-1.

This study shows that synthetic approaches to drug development are not always the norm, and that effective natural extracts such as Sphaeranthus Indicus have potential to become useful therapeutic agents. Sphira was shown to reduce pathogenic signal transduction responses that lead to inflammation in rheumatoid arthritis. This provides a reason for more research and clinical trials to be done on Sphira to perhaps introduce this agent to the market someday. This article also shows that cytokines can be useful drug targets, as they are involved in many signal transduction pathways that cause symptoms associated with disease. It is important as pharmacists to be educated on aspects of drug development and keep up to date on current research on potential therapeutic agents such as Sphira.

As a pharmacist, how would you go about informing a patient or student about natural extracts and their use in therapy and research?

Find the article here:

Trivedi J, Kharas F, Parikh S, et al.  Sphaeranthus indicus: Traditional Wisdom to Modern Medicine—An Orally Active, Potent Cytokine Inhibitor for the Management of Inflammatory Disorders. J. Pharm. Pharmacol  (7) 106-116. doi: 10.4236/pp.2016.72014

A Look into Neoadjuvant Trial Design and It’s Potential for Anticancer Drug Development

There is a very low success rate among anticancer agents in the drug development process, particularly between stage 2 and 3 clinical trials.  There is a noticeably lower success rate for oncology drugs to progress from one clinical trial to the next (57%) as compared to non-oncology medications.  Researchers at the Sloan Kettering Cancer Center in New York attempted to look for possible explanations for the phenomenon.  What they hypothesize is that the ability of clinical trials to predict the efficacy of novel drugs is inaccurate due to the outdated methods of determining end point response in solid tumors.  They assert that the current methods used, most notably the Response Evaluation Criteria in Solid Tumors (RECIST), were developed decades ago using arbitrary methods of grading tumor response that were never intended to be used for clinical significant outcomes.

The researchers suggest that improvements in the drug development process should start by using efficacy grading techniques that were intended for clinical outcomes, and are reflective of current capabilities in medical imaging.  The recommendation that they make involve using pathological complete response (pCR), which takes into account the effects that drugs have on metastatic cancer cells rather than just the impact on solid tumor tissue cells. This method is currently used for neoadjuvant trials, and could be used to predict improvements in overall survival for novel drug compounds.  In a review of numerous clinical studies the authors found usage of pCR methods in neoadjuvant methods to determine efficacy correlated to improved survival outcomes in breast cancer, muscle-invasive bladder cancer, and Non-small cell lung cancer.

The FDA has already approved pCR as a relevant indicator of neoadjuvant efficacy and as a surrogate indicator of increased survival in some breast cancer patients.  However, it is possible that this modern means of assessing cancer response could lead to an increase in the approval of new cancer drugs based on better ability to measure cancer response in patients.  The question that remains is: does this new method of efficacy evaluation seem like it will increase options for oncologists to improve survival rates, or is it possible that it will lower standards of approval to the detriment of cancer patients?

 Article Link

Funt, S. A., & Chapman, P. B. (2016). The Role of Neoadjuvant Trials in Drug Development for Solid Tumors. Clinl Cancer Res. 2016; Published OnlineFirst February 3, 2016; doi: 10.1158/1078-0432.CCR-15-196.