Efficacy, Safety of Baricitinib plus Remdesivir versus Standard Therapy (Remdesivir) in Patients with Severe COVID-19 Infection in Third Wave of Epidemics in Myanmar: Case Control Study
Main Article Content
Abstract
Background: Coronavirus disease 2019 (COVID-19) has been a major threat to health around the world as it causes significant morbidity and mortality. SARS-CoV-2 infection induces severe inflammation in lungs and multi-organs; therefore, the Janus kinase (JAK) inhibitor known as baricitinib was proposed as a treatment for COVID-19 because of its anti-inflammatory and potential antiviral effects. It may improve survival in patients with severe Covid-19 infection. The efficacy and safety of Baricitinib therapy in severe COVID-19 infection in Myanmar was not known clearly.
Methods: A case control study was conducted in COVID-19 treatment centers in Myanmar- Yangon and Nay Pyi Taw, from June to October 2021. Baricitinib 4 mg daily for 14 days was given to the patients with severe COVID-19 infection as an add on therapy to Standard treatment group (Remdesivir). The primary outcome was survival status; survive or non-survive. The secondary outcome was duration of hospital stay, the requirement for oxygen therapy at Day 7 (improved or not), changes in chest radiograph at Day 14 (improved, same or worse), and changes in inflammatory markers (CPR and LDH). Patient data were stratified by age, sex, body weight, co-morbidities and immune status (immunocompromised or normal immune status). Data were collected by using standardized forms and analysis was done.
Results: A total of 64 patients with severe COVID-19 infection were enrolled. Base line characteristics in both groups, Baricitinib group (n =32) and Standard treatment group (n = 32), were comparable. Nearly 53% of patients in Baricitinib group and 59% of patients in Standard treatment group survived; however, mean duration of hospital stay was shorter in Baricitinib group (15.53 ± 6.83 days versus 22.25 ± 11.17 days; p < 0.001). Improvement in oxygen supplementation, radiological changes and changes in inflammatory markers were not different in both groups. Minor side effects like giddiness, appetite loss and insomnia were noted in Baricitinib group.
Conclusions: In treating patients with severe COVID-19 infection, the survival rate was not different between Baricitinib group (Baricitinib plus Remdesivir) and Standard treatment group (Remdesivir). In survivors, those in Baricitinib group had shorter duration of hospital stays; quick recovery time and accelerating improvement in clinical status
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Bhaskar, S., Sinha, A., Banach, M., Mittoo, S., Weissert, R., Kass, J. S., Rajagopal, S., Pai, A. R., & Kutty, S. (2020). Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper. Frontiers in Immunology, 11, 1648.
https://doi.org/10.3389/fimmu.2020.01648
II. Chen, C., Wang, J., Li, H., Yuan, L., Gale, R. P., & Liang, Y. (2021). JAK-inhibitors for coronavirus disease-2019 (COVID-19): A meta-analysis. Leukemia, 35(9), 2616–2620.
https://doi.org/10.1038/s41375-021-01266-6
III. Chen, G., Wu, D., Guo, W., Cao, Y., Huang, D., Wang, H., Wang, T., Zhang, X., Chen, H., Yu, H., Zhang, X., Zhang, M., Wu, S., Song, J., Chen, T., Han, M., Li, S., Luo, X., Zhao, J., & Ning, Q. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of Clinical Investigation, 130(5), 2620–2629. PubMed. https://doi.org/10.1172/JCI137244
IV. García, L. F. (2020). Immune Response, Inflammation, and the Clinical Spectrum of COVID-19. Frontiers in Immunology, 11, 1441.
https://doi.org/10.3389/fimmu.2020.01441
V. Goletti, D., & Cantini, F. (2021). Baricitinib Therapy in Covid-19 Pneumonia—An Unmet Need Fulfilled. New England Journal of Medicine, 384(9), 867–869. https://doi.org/10.1056/NEJMe2034982
VI. Hasan, Md. J., Rabbani, R., Anam, A. M., Huq, S. M. R., Polash, M. M. I., Nessa, S. S. T., & Bachar, S. C. (2021). Impact of high dose of baricitinib in severe COVID-19 pneumonia: A prospective cohort study in Bangladesh. BMC Infectious Diseases, 21(1), 427. https://doi.org/10.1186/s12879-021-06119-2
VII. Iglesias Gómez, R., Méndez, R., Palanques-Pastor, T., Ballesta-López, O., Borrás Almenar, C., Megías Vericat, J. E., López-Briz, E., Font-Noguera, I., Menéndez Villanueva, R., Román Iborra, J. A., & Poveda Andrés, J. L. (2021). Baricitinib against severe COVID-19: Effectiveness and safety in hospitalised pretreated patients. European Journal of Hospital Pharmacy, ejhpharm-2021-002741.
https://doi.org/10.1136/ejhpharm-2021-002741
VIII. Jo, Y., Jamieson, L., Edoka, I., Long, L., Silal, S., Pulliam, J. R. C., Moultrie, H., Sanne, I., Meyer-Rath, G., & Nichols, B. E. (2021). Cost-effectiveness of Remdesivir and Dexamethasone for COVID-19 Treatment in South Africa. Open Forum Infectious Diseases, 8(3), ofab040.
https://doi.org/10.1093/ofid/ofab040
IX. Jorgensen, S. C. J., Tse, C. L. Y., Burry, L., & Dresser, L. D. (2020). Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. Pharmacotherapy, 40(8), 843–856.
https://doi.org/10.1002/phar.2438
X. Kalil, A. C., Patterson, T. F., Mehta, A. K., Tomashek, K. M., Wolfe, C. R., Ghazaryan, V., Marconi, V. C., Ruiz-Palacios, G. M., Hsieh, L., Kline, S., Tapson, V., Iovine, N. M., Jain, M. K., Sweeney, D. A., El Sahly, H. M., Branche, A. R., Regalado Pineda, J., Lye, D. C., Sandkovsky, U., … Beigel, J. H. (2021). Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. New England Journal of Medicine, 384(9), 795–807.
https://doi.org/10.1056/NEJMoa2031994
XI. Kelton, K., Klein, T., Murphy, D., Belger, M., Hille, E., McCollam, P. L., Spiro, T., & Burge, R. (2022). Cost-Effectiveness of Combination of Baricitinib and Remdesivir in Hospitalized Patients with COVID-19 in the United States: A Modelling Study. Advances in Therapy, 39(1), 562–582.
https://doi.org/10.1007/s12325-021-01982-6
XII. Mahase, E. (2022). Covid-19: Anti-inflammatory treatment baricitinib reduces deaths in patients admitted to hospital, finds trial. BMJ, 376, o573. https://doi.org/10.1136/bmj.o573
XIII. Marconi, V. C., Ramanan, A. V., de Bono, S., Kartman, C. E., Krishnan, V., Liao, R., Piruzeli, M. L. B., Goldman, J. D., Alatorre-Alexander, J., de Cassia Pellegrini, R., Estrada, V., Som, M., Cardoso, A., Chakladar, S., Crowe, B., Reis, P., Zhang, X., Adams, D. H., Ely, E. W., & on behalf of the COV-BARRIER Study Group. (2021). Baricitinib plus Standard of Care for Hospitalized Adults with COVID-19. MedRxiv, 2021.04.30.21255934.
https://doi.org/10.1101/2021.04.30.21255934
XIV. Ohsfeldt, R., Kelton, K., Klein, T., Belger, M., Mc Collam, P. L., Spiro, T., Burge, R., & Ahuja, N. (2021). Cost-Effectiveness of Baricitinib Compared With Standard of Care: A Modeling Study in Hospitalized Patients With COVID-19 in the United States. Clinical Therapeutics, 43(11), 1877-1893.e4. https://doi.org/10.1016/j.clinthera.2021.09.016
XV. Pérez-Alba, E., Nuzzolo-Shihadeh, L., Aguirre-García, G. M., Espinosa-Mora, J., Lecona-Garcia, J. D., Flores-Pérez, R. O., Mendoza-Garza, M., & Camacho-Ortiz, A. (2021). Baricitinib plus dexamethasone compared to dexamethasone for the treatment of severe COVID-19 pneumonia: A retrospective analysis. Journal of Microbiology, Immunology and Infection, 54(5), 787–793. https://doi.org/10.1016/j.jmii.2021.05.009
XVI. Petrone, L., Petruccioli, E., Alonzi, T., Vanini, V., Cuzzi, G., Najafi Fard, S., Castilletti, C., Palmieri, F., Gualano, G., Vittozzi, P., Nicastri, E., Lepore, L., Grifoni, A., Antinori, A., Vergori, A., Ippolito, G., Cantini, F., & Goletti, D. (2021). In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy. Journal of Infection, 82(4), 58–66.
https://doi.org/10.1016/j.jinf.2021.02.023
XVII. Thant, P. W., Htet, K. T., Win, W. Y., Htwe, Y. M., & Htoo, T. S. (2021). Cost estimates of COVID-19 clinical management in Myanmar. BMC Health Services Research, 21(1), 1365.
https://doi.org/10.1186/s12913-021-07394-0
XVIII. Titanji, B. K., Farley, M. M., Mehta, A., Connor-Schuler, R., Moanna, A., Cribbs, S. K., O’Shea, J., DeSilva, K., Chan, B., Edwards, A., Gavegnano, C., Schinazi, R. F., & Marconi, V. C. (2021). Use of Baricitinib in Patients With Moderate to Severe Coronavirus Disease 2019. Clinical Infectious Diseases, 72(7), 1247–1250.
https://doi.org/10.1093/cid/ciaa879
XIX. Tziolos, N., Karofylakis, E., Grigoropoulos, I., Kazakou, P., Koullias, E., Savva, A., Kranidioti, H., Pelekanou, A., Boulouta, A., Pirounaki, M., Tsiodras, S., Georgiopoulos, G., Boumpas, D. T., Kavatha, D., Thomas, K., Vassilopoulos, D., & Antoniadou, A. (2022). Real-Life Effectiveness and Safety of Baricitinib as Adjunctive to Standard-of-Care Treatment in Hospitalized Patients With Severe Coronavirus Disease 2019. Open Forum Infectious Diseases, 9(1), ofab588.
https://doi.org/10.1093/ofid/ofab588
XX. Vandepitte, S., Alleman, T., Nopens, I., Baetens, J., Coenen, S., & De Smedt, D. (2021). Cost-Effectiveness of COVID-19 Policy Measures: A Systematic Review. Value in Health : The Journal of the International Society for Pharmacoeconomics and Outcomes Research, 24(11), 1551–1569. PubMed. https://doi.org/10.1016/j.jval.2021.05.013
XXI. Wu, Y., Huang, X., Sun, J., Xie, T., Lei, Y., Muhammad, J., Li, X., Zeng, X., Zhou, F., Qin, H., Shao, L., & Zhang, Q. (2020). Clinical Characteristics and Immune Injury Mechanisms in 71 Patients with COVID-19. MSphere, 5(4).