Session Type: Abstract Submissions (ACR)
Background/Purpose: Development of new SLE treatments has been slow with only one new treatment approved in the past half century. One way to increase the availability of new therapies for SLE is to consider repositioning agents that have been approved for other indications. The goal of this project was to identify possible therapies that might be useful as therapies for lupus among the hundreds of agents approved for human use.
Methods: Initially, a comprehensive strategy was developed to identify all possible SLE therapies within FDA approved drugs and therapies. First, the lupus community was engaged via a social media site (www.linkedin.com/in/lrxlstat) and queried for recommendations. Secondly, the reported actions of all drugs approved for human used were cross-referenced with a database of known pathway abnormalities in SLE. Finally a comprehensive search of all drugs and therapies showing benefit in murine models of SLE was carried out. After the initial Lupus Treatment List (LRxL) was assembled, a structured research of the available literature on each drug and therapy was carried out focusing on mechanism of action, relevant experience in animals and humans, drug properties and adverse events. Finally, a comprehensive scoring system was developed and employed to score ten features of each drug or therapy on a 28 point scale. Face validity of this scoring system was assessed by ranking available lupus therapies and questioning rheumatologists for their response.
Results: Of the more than 1100 new chemical entities approved by the FDA for 6800 indications, 157 were identified as possible treatments for SLE. All drugs widely used for lupus or known to be in development for lupus by Pharma/Biotech were excluded. Of the 157 therapies initially screened, more than 25 have an appropriate set of characteristics to consider for testing in clinical trials in lupus, including drugs targeting cellular metabolism, kinases, cytokines, immune cell function and regulation, HDACs, complement as well as cellular therapies & non-drug/cell interventions.
Conclusion: This approach has demonstrated that there are numerous FDA-approved candidates for repositioning as new therapies for SLE. Not only have unique treatments that could be useful in SLE and possibly other autoimmune/inflammatory conditions been identified, but a rigorous evidence-based process has been delineated by which therapies can be objectively rated for possible clinical application to treat these conditions, thereby miti
P. E. Lipsky,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-strategy-to-identify-and-evaluate-approved-drugs-and-treatments-for-repositioning-as-therapies-for-systemic-lupus-erythematosus-sle/