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- Page navigation anchor for RE: Managing drug shortages during a pandemic: tocilizumab and COVID-19 -- Consider the doseRE: Managing drug shortages during a pandemic: tocilizumab and COVID-19 -- Consider the dose
We read with great interest the Analysis article by Verma et al.(1) The authorship team must be lauded for undertaking a difficult topic and for developing a systematic approach to allocation of a scarce drug resource. However, the article fails to consider an important alternative view, which is that the tocilizumab dose used in all published randomized trials to date may be excessive, perhaps by as much as ten-fold.(2)
The authors’ attempts to estimate the available drug supply fail without this consideration. One must differentiate between “nominal supply” (the raw amount of drug present) and “effective supply” (the number of patients one can treat with that raw amount of drug).(2) In the case of tocilizumab and other absolutely scarce drugs, the informational gap between nominal supply and effective supply can be systematically filled by appropriately conducted randomized dose-ranging clinical trials.
Therefore, the question of whether Canada (or any country for that matter) has “enough” or “not enough” tocilizumab must consider the effective dose. We have suggested that the effective dose of tocilizumab may be as low as 40 mg (i.e., 10% of the commonly prescribed 400mg dose), as based on both our understanding of the pharmacokinetics and pharmacodynamics of tocilizumab,(2) as well as a nonrandomized dose de-escalation study.(3) In truth, the effective supply of tocilizumab may be an order of magnitude higher than currently estimated. A randomized, contro...
Show MoreCompeting Interests: The authors are listed co-inventors on a filed patent covering low-dose tocilizumab in viral infections, held by the University of Chicago. GWS is an employee of the United States Government. The comments contained herein do not reflect those of the U.S. Government.References
- Amol A. Verma, Menaka Pai, Sudipta Saha, et al. Managing drug shortages during a pandemic: tocilizumab and COVID-19. CMAJ 2021;10.1503/cmaj.210531.
- Strohbehn GW, Reid PD, Ratain MJ. Applied clinical pharmacology in a crisis: Interleukin-6 axis blockade and COVID-19. Clin Pharmacol Therapeut 2020:1-9. DOI: 10.1002/CPT.1931.
- Strohbehn GW, Heiss BL, Rouhani SJ, et al. COVIDOSE: A phase 2 clinical trial of low-dose tocilizumab in the treatment of non-critical COVID-19 pneumonia. Clin Pharmacol Ther 2020 (In eng). DOI: 10.1002/cpt.2117.
- ClinicalTrials.gov. Low-dose Tocilizumab versus Standard of Care in Hospitalized Patients with COVID-19 (COVIDOSE-2). U.S. National Library of Medicine. (https://clinicaltrials.gov/ct2/show/NCT04479358).