With doctors and researchers around the world searching for effective treatments for COVID-19, many drugs approved to treat other diseases are being used in hopes that they'll be effective against the virus, a use that's known as "off-label." New research from the Perelman School of Medicine at the University of Pennsylvania catalogued every use documented in medical literature so far and found physicians have reported on the use of more than 100 different off-label and experimental treatments.
The effort, called COvid19 Registry of Off-label & New Agents (CORONA), is an attempt to take an inventory of what's being used where, as well as to spot any evidence of treatments that warrant further investigation in a randomised clinical trial.
"We can't win this fight if we don't take stock of the tools that are already being used and search for new ones that could be effective. While off-label use is happening all over the world, there's currently no system in place to track it, so we felt like we had to create one," said the study's lead author Dr David C Fajgenbaum, an assistant professor of translational medicine & human genetics and director of the Centre for Cytokine Storm Treatment & Laboratory (CSTL) at Penn.
Fajgenbaum is also the executive director of the Castleman Disease Collaborative Network (CDCN) and a Castleman patient himself. In 2012, after failing to respond to other therapies and having relapsed multiple times after chemo, Fajgenbaum's research suggested a drug approved for other uses may be effective for his condition. Based on his own research and in consultation with his treating physician, Fajgenbaum decided to test the drug on himself and has been in remission ever since.
"With the world facing its greatest public health crisis in a century, we decided to take action, using the same approach that helped me and applying it to potentially help find promising leads in the treatment of COVID-19," Fajgenbaum said.
The team reviewed about 2,700 published papers from all over the world detailing the treatment of COVID-19. From there, they gathered data on 9,152 patients and found doctors had tried 115 different drugs. These treatments were grouped into categories — antivirals were unsurprisingly the most common, followed by antibacterials and corticosteroids. The analysis also showed the use of immunosuppressants and blood substitutes, among other treatment options. Dr Sheila Pierson, the associate director for clinical research at the CSTL, director of registry enrolment for the CDCN, and the study's senior author, led the analysis of the data.
"Our team has spent the last several years studying drugs used to control the cytokine storm in Castleman disease, so I'm glad we were able to apply these principles to COVID19. The work remains ongoing, and we are updating this drug inventory daily as we continue to compile information on other treatments as they're being reported in the medical literature," Pierson said.
Fajgenbaum notes that the goal of this work is not to point toward the most effective treatment, but to provide a resource for what may be candidates for further study. "We hear a lot about the same handful of drugs, but we show here that there are many more currently in use than those that have already made headlines. Anything that shows promise anecdotally still needs to be rigorously tested in a clinical trial to see if it is effective and safe," Fajgenbaum said.
Abstract
The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA. Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols.
Authors
David C Fajgenbaum, Johnson S Khor, Alexander Gorzewski, Mark-Avery Tamakloe, Victoria Powers, Joseph J Kakkis, Mileva Repasky, Anne Taylor, Alexander Beschloss, Laura Hernandez-Miyares, Beatrice Go, Vivek Nimgaonkar, Madison S McCarthy, Casey J Kim, Ruth-Anne Langan Pai, Sarah Frankl, Philip Angelides, Joanna Jiang, Rozena Rasheed, Erin Napier, Duncan Mackay, Sheila K Pierson
[link url="https://www.pennmedicine.org/news/news-releases/2020/may/taking-inventory-of-which-drugs-the-world-is-using-to-treat-covid19"]University of Pennsylvania School of Medicine material[/link]
[link url="https://link.springer.com/article/10.1007/s40121-020-00303-8"]Inectious Disease and Therapy abstract[/link]