Applied Clinical Pharmacology in a Crisis: Interleukin-6 Axis Blockade and COVID-19

Garth W Strohbehn, Pankti D Reid, Mark J Ratain, Garth W Strohbehn, Pankti D Reid, Mark J Ratain

Abstract

The global pandemic of coronavirus disease 2019 (COVID-19) represents an emergent threat to the public health. Mitigation strategies have been employed to varying effect in many Western nations. Treatment strategies to effectively address COVID-19 and equitably distribute resources are needed, especially in overwhelmed hospitals.

Conflict of interest statement

G.W.S. is supported by the Richard and Debra Gonzalez Research Fellowship at the University of Chicago (established through philanthropy by Abbott Laboratories; Lake Bluff, Illinois, USA). P.D.R. declared no competing interests for this work. M.J.R. reports personal fees from Apotex, personal fees from Ascentage, personal fees from Teva, personal fees from Cyclacel, personal fees from Celltrion, personal fees from Breckenridge, personal fees from Par Pharmaceuticals, personal fees from Roxane, personal fees from Aptevo, personal fees from Accord, personal fees from Actavis, personal fees from Amerigen, personal fees from Argentum, personal fees from BPI Labs, personal fees from Belcher, personal fees from Dr. Reddy's, personal fees from Fresenius Kabi, personal fees from Glenmark, personal fees from Hetero, personal fees from Mylan, personal fees from Sandoz, personal fees from Pneuma Respiratory, personal fees from Shionogi, personal fees from Aurobindo, grants from AbbVie, grants from Dicerna, grants from Genentech, grants from Xencor, other from BeiGene, outside the submitted work; In addition, M.J.R. has a patent US6395481B1 with royalties paid to Mayo Medical, a patent EP1629111B1 with royalties paid to Mayo Medical, a patent US8877723B2 issued, and a patent US9617583B2 issued and is Director and Treasurer, Value in Cancer Care Consortium. All authors are coinventors on a provisional patent entitled, “Tocilizumab for the Treatment of Viral Infections” filed by The University of Chicago.

© 2020 The Authors. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1
Figure 1
Proposed treatment strategy for patients with moderate or severe COVID‐19 with high risk for clinical decompensation using tocilizumab titration. Most hospitalized patients with COVID‐19 infections are potential recipients of IL‐6 axis‐suppressing therapy, with priority for those patients at high risk for decompensation and death. Following baseline clinical and laboratory‐based risk stratification, patients will receive an initial dose of tocilizumab. Studies need to be performed to determine the minimum effective dose in this context, but it may be 100 mg or lower. Supportive clinical care continues for 24 hours after the initial tocilizumab dose, at which point repeat clinical and biochemical assessments are performed. If clinical stability or clinical improvement and biochemical evidence of IL‐6 axis suppression, continuation of supportive clinical care without repeat dosing is indicated. If clinical decompensation or biochemical evidence of insufficient IL‐6 axis suppression, patients receive an additional dose of tocilizumab, with reconsideration of additional doses at 24‐hour intervals. COVID‐19, coronavirus disease 2019; h, hours; PaO2, arterial oxygen partial pressure; SpO2, peripheral blood oxygen saturation; Temp, temperature.

References

    1. Beigel, J.H. et al. Remdesivir for the Treatment of Covid‐19 — Preliminary Report. N. Engl. J. Med. (2020). 10.1056/NEJMoa2007764
    1. Mehta, P. , McAuley, D.F. , Brown, M. , Sanchez, E. , Tattersall, R.S. & Manson, J.J. COVID‐19: consider cytokine storm syndromes and immunosuppression. Lancet 395, 1033–1034 (2020).
    1. Liu, F. et al. Prognostic value of interleukin‐6, C‐reactive protein, and procalcitonin in patients with COVID‐19. J. Clin. Virol. 127, 104370 (2020).
    1. Xu, X. et al. Effective treatment of severe COVID‐19 patients with tocilizumab. Proc. Natl. Acad. Sci. U.S.A. 117, 10970–10975 (2020).
    1. Hoffmann‐La Roche . A study to evaluate the safety and efficacy of tocilizumab in patients with severe covid‐19 pneumonia (COVACTA). Available from: . NLM identifier: NCT04320615. Accessed March 30, 2020.
    1. Ratain, M.J. , Goldstein, D.A. & Lichter, A.S. Interventional pharmacoeconomics—A new discipline for a cost‐constrained environment. JAMA Oncol. 5, 1097–1098 (2019).
    1. US Food and Drug Administration . Multi‐disciplinary review: application number BLA 125276 S‐114. In (eds Center for Drug Evaluation and Research . Silver Spring, Maryland: ) (Food and Drug Administration of the United States of America, 2017) 41–43.
    1. Bastida, C. , Soy, D. , Ruiz‐Esquide, V. , Sanmartí, R. & Huitema, A.D.R. Exposure‐response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components. Br. J. Clin. Pharmacol. 85, 1710–1718 (2019).
    1. Nishimoto, N. et al. Toxicity, pharmacokinetics, and dose‐finding study of repetitive treatment with the humanized anti‐interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J. Rheumatol. 30, 1426–1435 (2003).
    1. Zeng, C. et al. Efficacy and toxicity for CD22/CD19 chimeric antigen receptor T‐cell therapy in patients with relapsed/refractory aggressive B‐cell lymphoma involving the gastrointestinal tract. Cytotherapy 22, 166–171 (2020).
    1. University of Chicago . Tocilizumab to prevent clinical decompensation in hospitalized, non‐critically ill patients with COVID‐19 pneumonitis (COVIDOSE). Available from: . NLM identifier: NCT 04331795. Accessed May 18, 2020.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren