Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial

Alex L. E. Halme; Sanna Laakkonen; Jarno Rutanen; Olli P. O. Nevalainen; Marjatta Sinisalo; Saana Horstia; Jussi M. J. Mustonen; Negar Pourjamal; Aija Vanhanen; Solidarity Finland Investigators; Tuomas Rosberg; Andreas Renner; Markus Perola; Erja-Leena Paukkeri; Riitta-Liisa Patovirta; Seppo Parkkila; Juuso Paajanen; Taina Nykänen; Jarkko Mäntylä; Marjukka Myllärniemi; Tiina Mattila; Maarit K. Leinonen; Alvar Külmäsu; Pauliina Kuutti; Ilari Kuitunen; Hanna-Riikka Kreivi; Tuomas P. Kilpeläinen; Heikki Kauma; Ilkka E. J. Kalliala; Petrus Järvinen; Riina Hankkio; Taina Hammarén; Thijs Feuth; Hanna Ansakorpi; Riikka Ala-Karvia; Gordon H. Guyatt; Kari A. O. Tikkinen

doi:10.1016/j.jinf.2024.106217

Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial

Alex L. E. Halme, Sanna Laakkonen, Jarno Rutanen, Olli P. O. Nevalainen, Marjatta Sinisalo, Saana Horstia, Jussi M. J. Mustonen, Negar Pourjamal, Aija Vanhanen, Solidarity Finland Investigators, Tuomas Rosberg, Andreas Renner, Markus Perola, Erja-Leena Paukkeri, Riitta-Liisa Patovirta, Seppo Parkkila, Juuso Paajanen, Taina Nykänen, Jarkko Mäntylä, Marjukka MyllärniemiTiina Mattila, Maarit K. Leinonen, Alvar Külmäsu, Pauliina Kuutti, Ilari Kuitunen, Hanna-Riikka Kreivi, Tuomas P. Kilpeläinen, Heikki Kauma, Ilkka E. J. Kalliala, Petrus Järvinen, Riina Hankkio, Taina Hammarén, Thijs Feuth, Hanna Ansakorpi, Riikka Ala-Karvia, Gordon H. Guyatt, Kari A. O. Tikkinen

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47–3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78–1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.

Original language	English
Article number	106217
Journal	Journal of Infection
Volume	89
Issue number	3
Number of pages	9
ISSN	0163-4453
DOIs	https://doi.org/10.1016/j.jinf.2024.106217
Publication status	Published - Sept 2024
MoE publication type	A1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Fields of Science

Clinical Trials
COVID-19
Imatinib
Immunomodulatory effects
Long COVID patient outcomes
Post-acute COVID syndrome
Post-COVID
Randomized controlled trial
SARS-CoV-2 infection
Tyrosine kinase inhibitors
3121 General medicine, internal medicine and other clinical medicine

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10.1016/j.jinf.2024.106217

1-s2.0-S0163445324001518-mainFinal published version, 825 KBLicence: CC BY

Cite this

Halme, A. L. E., Laakkonen, S., Rutanen, J., Nevalainen, O. P. O., Sinisalo, M., Horstia, S., Mustonen, J. M. J., Pourjamal, N., Vanhanen, A., Solidarity Finland Investigators, Rosberg, T., Renner, A., Perola, M., Paukkeri, E.-L., Patovirta, R.-L., Parkkila, S., Paajanen, J., Nykänen, T., Mäntylä, J., ... Tikkinen, K. A. O. (2024). Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial. Journal of Infection, 89(3), Article 106217. https://doi.org/10.1016/j.jinf.2024.106217

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title = "Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial",

abstract = "Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2\% had died at 30 days and 13.3\% at 1 year, and in SoC, 4.1\% and 8.2\% (adjusted HR 1.35, 95\% CI 0.47–3.90). At 1 year, self-reported recovery occurred in 79.0\% in imatinib and in 88.5\% in SoC (RR 0.91, 0.78–1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24\%) and sleep issues (20\%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.",

keywords = "Clinical Trials, COVID-19, Imatinib, Immunomodulatory effects, Long COVID patient outcomes, Post-acute COVID syndrome, Post-COVID, Randomized controlled trial, SARS-CoV-2 infection, Tyrosine kinase inhibitors, 3121 General medicine, internal medicine and other clinical medicine",

author = "Halme, \{Alex L. E.\} and Sanna Laakkonen and Jarno Rutanen and Nevalainen, \{Olli P. O.\} and Marjatta Sinisalo and Saana Horstia and Mustonen, \{Jussi M. J.\} and Negar Pourjamal and Aija Vanhanen and \{Solidarity Finland Investigators\} and Tuomas Rosberg and Andreas Renner and Markus Perola and Erja-Leena Paukkeri and Riitta-Liisa Patovirta and Seppo Parkkila and Juuso Paajanen and Taina Nyk{\"a}nen and Jarkko M{\"a}ntyl{\"a} and Marjukka Myll{\"a}rniemi and Tiina Mattila and Leinonen, \{Maarit K.\} and Alvar K{\"u}lm{\"a}su and Pauliina Kuutti and Ilari Kuitunen and Hanna-Riikka Kreivi and Kilpel{\"a}inen, \{Tuomas P.\} and Heikki Kauma and Kalliala, \{Ilkka E. J.\} and Petrus J{\"a}rvinen and Riina Hankkio and Taina Hammar{\'e}n and Thijs Feuth and Hanna Ansakorpi and Riikka Ala-Karvia and Guyatt, \{Gordon H.\} and Tikkinen, \{Kari A. O.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = sep,

doi = "10.1016/j.jinf.2024.106217",

language = "English",

volume = "89",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders Ltd",

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Halme, ALE, Laakkonen, S, Rutanen, J, Nevalainen, OPO, Sinisalo, M, Horstia, S, Mustonen, JMJ, Pourjamal, N, Vanhanen, A, Solidarity Finland Investigators, Rosberg, T, Renner, A , Perola, M, Paukkeri, E-L, Patovirta, R-L, Parkkila, S, Paajanen, J, Nykänen, T , Mäntylä, J , Myllärniemi, M , Mattila, T , Leinonen, MK, Külmäsu, A, Kuutti, P, Kuitunen, I, Kreivi, H-R, Kilpeläinen, TP, Kauma, H, Kalliala, IEJ , Järvinen, P, Hankkio, R, Hammarén, T, Feuth, T, Ansakorpi, H, Ala-Karvia, R, Guyatt, GH & Tikkinen, KAO 2024, 'Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial', Journal of Infection, vol. 89, no. 3, 106217. https://doi.org/10.1016/j.jinf.2024.106217

TY - JOUR

T1 - Short- and long-term effects of imatinib in hospitalized COVID-19 patients

T2 - A randomized trial

AU - Halme, Alex L. E.

AU - Laakkonen, Sanna

AU - Rutanen, Jarno

AU - Nevalainen, Olli P. O.

AU - Sinisalo, Marjatta

AU - Horstia, Saana

AU - Mustonen, Jussi M. J.

AU - Pourjamal, Negar

AU - Vanhanen, Aija

AU - Solidarity Finland Investigators

AU - Rosberg, Tuomas

AU - Renner, Andreas

AU - Perola, Markus

AU - Paukkeri, Erja-Leena

AU - Patovirta, Riitta-Liisa

AU - Parkkila, Seppo

AU - Paajanen, Juuso

AU - Nykänen, Taina

AU - Mäntylä, Jarkko

AU - Myllärniemi, Marjukka

AU - Mattila, Tiina

AU - Leinonen, Maarit K.

AU - Külmäsu, Alvar

AU - Kuutti, Pauliina

AU - Kuitunen, Ilari

AU - Kreivi, Hanna-Riikka

AU - Kilpeläinen, Tuomas P.

AU - Kauma, Heikki

AU - Kalliala, Ilkka E. J.

AU - Järvinen, Petrus

AU - Hankkio, Riina

AU - Hammarén, Taina

AU - Feuth, Thijs

AU - Ansakorpi, Hanna

AU - Ala-Karvia, Riikka

AU - Guyatt, Gordon H.

AU - Tikkinen, Kari A. O.

PY - 2024/9

Y1 - 2024/9

N2 - Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47–3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78–1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.

AB - Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47–3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78–1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.

KW - Clinical Trials

KW - COVID-19

KW - Imatinib

KW - Immunomodulatory effects

KW - Long COVID patient outcomes

KW - Post-acute COVID syndrome

KW - Post-COVID

KW - Randomized controlled trial

KW - SARS-CoV-2 infection

KW - Tyrosine kinase inhibitors

KW - 3121 General medicine, internal medicine and other clinical medicine

U2 - 10.1016/j.jinf.2024.106217

DO - 10.1016/j.jinf.2024.106217

M3 - Article

C2 - 38969238

AN - SCOPUS:85200635763

SN - 0163-4453

VL - 89

JO - Journal of Infection

JF - Journal of Infection

IS - 3

M1 - 106217

ER -