Colchicine as adjuvant therapy in COVID-19 patients: A meta-analysis

Betty Rachma, Probo Yudha Pratama Putra, Zakiya Zulaifah, Arlinda Silva Prameswari, Dinda Amalia Eka Putri

Abstract


SARS CoV-2 infection results in hyperinflammatory responses through the activation of proinflammatory cytokines and chemokines. Colchicine is an anti-inflammatory drug that reduces superoxide production, TNF-a activation, and neutrophil chemotaxis. This study aims to determine the effect of adjuvant colchicine on mortality in COVID-19 patients. Systematic literature searching was conducted on PubMed, ScienceDirect, Cochrane Library, and medRxiv with keywords colchicine, Coronavirus Disease, COVID-19, SARS CoV-2, and mortality. Five randomized controlled studies with 15.779 patients were included. There was no significant difference between colchicine group and standard group (OR 1.00 [95% CI 0.91-1.09], p=0.94), Invasive mechanical ventilation necessity also did not show significant difference (OR 0.99 [95% CI 0.83-1.17 p=0.88). There was no significant difference in the incidence of cardiovascular disease (OR 1.11 [95% CI 0.50-2.46], p = 0.79), also the incidence of pneumonia was lower in colchicine group (OR 0.68 [95% CI 0.49-0.93], p=0.02), while the incidence of gastrointestinal complaints was higher in colchicine group (OR 2.09 [95% CI 1.84-2.37], p<0.00001). Colchicine as COVID-19 adjuvant therapy did not significantly reduce mortality, the need for invasive mechanical ventilation, and the incidence of cardiovascular disease. Furthermore, the colchicine group had lower pneumonia incidence and higher gastrointestinal complaints incidence.

References


T. Asselah, D. Durantel, E. Pasmant, G. Lau, and R. F. Schinazi, “COVID-19: Discovery, diagnostics and drug development,” J. Hepatol., vol. 74, pp. 168–184, 2021, doi: 10.1016/j.jhep.2020.09.031.

M. E. Fernández-Cuadros et al., “Colchicine-Induced Rhabdomyolysis: Clinical, Biochemical, and Neurophysiological Features and Review of the Literature,” Clin. Med. Insights Arthritis Musculoskelet. Disord., vol. 12, 2019, doi: 10.1177/1179544119849883.

R. Collaborative Group, “Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial,” 2021, doi: 10.1016/S2213-2600(21)00435-5.

S. Hojyo et al., “How COVID-19 induces cytokine storm with high mortality,” Inflamm. Regen., vol. 40, no. 1, Oct. 2020, doi: 10.1186/S41232-020-00146-3.

R. Nadeem et al., “Prediction of Cytokine Storm and Mortality in Patients with COVID-19 Admitted to ICU: Do Markers Tell the Story?,” Dubai Med. J., vol. 4, no. 2, pp. 142–150, Apr. 2021, doi: 10.1159/000514406.

V. J. Costela-Ruiz, R. Illescas-Montes, J. M. Puerta-Puerta, C. Ruiz, and L. Melguizo-Rodríguez, “SARS-CoV-2 infection: The role of cytokines in COVID-19 disease,” Cytokine Growth Factor Rev., vol. 54, p. 62, Aug. 2020, doi: 10.1016/J.CYTOGFR.2020.06.001.

A. A. Rabaan et al., “Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm,” Vaccines 2021, Vol. 9, Page 436, vol. 9, no. 5, p. 436, Apr. 2021, doi: 10.3390/VACCINES9050436.

J. B. Moore and C. H. June, “Cytokine release syndrome in severe COVID-19,” Science, vol. 368, no. 6490, pp. 473–474, May 2020, doi: 10.1126/SCIENCE.ABB8925.

D. C. Fajgenbaum and C. H. June, “Cytokine Storm,” N. Engl. J. Med., vol. 383, no. 23, pp. 2255–2273, Dec. 2020, doi: 10.1056/NEJMRA2026131/SUPPL_FILE/NEJMRA2026131_DISCLOSURES.PDF.

S. Surma, M. Basiak, M. Romańczyk, K. J. Filipiak, and B. Okopień, “Colchicine — From rheumatology to the new kid on the block: Coronary syndromes and COVID-19,” Cardiol. J., Oct. 2021, doi: 10.5603/CJ.A2021.0123.

M. Scarsi et al., “Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome,” Ann. Rheum. Dis., vol. 79, no. 10, pp. 1286–1289, Oct. 2020, doi: 10.1136/ANNRHEUMDIS-2020-217712.

A. Vitiello and F. Ferrara, “Colchicine and SARS-CoV-2: Management of the hyperinflammatory state,” Respir. Med., vol. 178, p. 106322, Mar. 2021, doi: 10.1016/J.RMED.2021.106322.

M. J. Page et al., “The PRISMA 2020 statement: An updated guideline for reporting systematic reviews,” Int. J. Surg., vol. 88, no. March, 2021, doi: 10.1016/j.ijsu.2021.105906.

J. P. T. Higgins et al., “The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials,” BMJ, vol. 343, no. 7829, pp. 1–9, 2011, doi: 10.1136/bmj.d5928.

D. A. Pascual-Figal et al., “Colchicine in recently hospitalized patients with COVID-19: A randomized controlled trial (COL-COVID),” Int. J. Gen. Med., vol. 14, no. August, pp. 5517–5526, 2021, doi: 10.2147/IJGM.S329810.

S. G. Deftereos et al., “Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial,” JAMA Netw. Open, vol. 3, no. 6, pp. e2013136–e2013136, Jun. 2020, doi: 10.1001/JAMANETWORKOPEN.2020.13136.

P. W. Horby et al., “Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial,” medRxiv, p. 2021.05.18.21257267, May 2021, doi: 10.1101/2021.05.18.21257267.

M. I. Lopes et al., “Beneficial effects of colchicine for moderate to severe COVID-19: A randomised, double-blinded, placebo-controlled clinical trial,” RMD Open, vol. 7, no. 1, pp. 1–8, 2021, doi: 10.1136/rmdopen-2020-001455.

J.-C. J.-D. D. C. Tardif et al., “Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial,” Lancet Respir. Med., vol. 0, no. 0, pp. 924–932, May 2021, doi: 10.1016/S2213-2600(21)00222-8.

N. Schlesinger, B. L. Firestein, and L. Brunetti, “Colchicine in COVID-19: an Old Drug, New Use,” Curr. Pharmacol. Reports, vol. 6, no. 4, p. 1, Aug. 2020, doi: 10.1007/S40495-020-00225-6.

L. Manenti et al., “Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study,” PLoS One, vol. 16, no. 3 March, pp. 1–11, Mar. 2021, doi: 10.1371/journal.pone.0248276.

M. Richter et al., “Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents,” ChemMedChem, vol. 14, no. 4, pp. 469–483, 2019, doi: 10.1002/cmdc.201800641.

C. Perricone et al., “The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19,” J. Autoimmun., vol. 111, p. 102468, Jul. 2020, doi: 10.1016/J.JAUT.2020.102468.

A. Munjal et al., “Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives,” Front. Microbiol., vol. 8, no. AUG, Aug. 2017, doi: 10.3389/FMICB.2017.01469.

Y. Y. Leung, L. L. Yao Hui, and V. B. Kraus, “Colchicine-Update on mechanisms of action and therapeutic uses,” Semin. Arthritis Rheum., vol. 45, no. 3, pp. 341–350, Dec. 2015, doi: 10.1016/j.semarthrit.2015.06.013.

I. Chen, M. Moriyama, M. Chang, and T. Ichinohe, “Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome,” vol. 10, no. November 2002, pp. 1–9, 2019, doi: 10.3389/fmicb.2019.00050.

C. Castaño-Rodriguez et al., “Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis,” MBio, vol. 9, no. 3, May 2018, doi: 10.1128/MBIO.02325-17.

M. C. Cure, A. Kucuk, and E. Cure, “Colchicine may not be effective in COVID-19 infection; it may even be harmful?”,” Clin. Rheumatol., vol. 39, no. 8, pp. 2487–2488, 2020, doi: 10.1007/s10067-020-05144-x.

R. A. Siemieniuk et al., “Drug treatments for covid-19: living systematic review and network meta-analysis,” doi: 10.1136/bmj.m2980.

M. Fioranelli, A. G. Bottaccioli, F. Bottaccioli, M. Bianchi, M. Rovesti, and M. G. Roccia, “Stress and inflammation in coronary artery disease: A review psychoneuroendocrineimmunology-based,” Front. Immunol., vol. 9, no. SEP, p. 2031, Sep. 2018, doi: 10.3389/FIMMU.2018.02031/BIBTEX.

E. Della-Torre et al., “Treating COVID-19 with colchicine in community healthcare setting,” Clin. Immunol., vol. 217, p. 108490, 2020, doi: https://doi.org/10.1016/j.clim.2020.108490.

P. M. Ridker et al., “Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease,” N. Engl. J. Med., vol. 377, no. 12, pp. 1119–1131, 2017, doi: 10.1056/nejmoa1707914.

S. J. Kottoor and R. R. Arora, “The Utility of Anti-Inflammatory Agents in Cardiovascular Disease: A Novel Perspective on the Treatment of Atherosclerosis,” J. Cardiovasc. Pharmacol. Ther., vol. 23, no. 6, pp. 483–493, Nov. 2018, doi: 10.1177/1074248418778548.

I. Wudexi, E. Shokri, M. Abo-Aly, K. Shindo, and A. Abdel-Latif, “Comparative Effectiveness of Anti-Inflammatory Drug Treatments in Coronary Heart Disease Patients: A Systematic Review and Network Meta-Analysis,” Mediators Inflamm., vol. 2021, 2021, doi: 10.1155/2021/5160728.

M. Imazio et al., “Anti-inflammatory therapies for pericardial diseases in the COVID-19 pandemic: safety and potentiality,” J. Cardiovasc. Med. (Hagerstown)., vol. 21, no. 9, pp. 625–629, Sep. 2020, doi: 10.2459/JCM.0000000000001059.

P. C. Robinson et al., “Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease,” Am. J. Med., vol. 135, no. 1, pp. 32–38, Jan. 2022, doi: 10.1016/J.AMJMED.2021.07.025.

A. T. L. Fiolet et al., “Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials,” Eur. Heart J., vol. 42, no. 28, pp. 2765–2775, Jul. 2021, doi: 10.1093/EURHEARTJ/EHAB115.

S. M. Nidorf et al., “Colchicine in Patients with Chronic Coronary Disease,” N. Engl. J. Med., vol. 383, no. 19, pp. 1838–1847, 2020, doi: 10.1056/nejmoa2021372.

“Colchicine vs Current Standard of Care in Hospitalized Patients With COVID-19 and Cardiac Injury - Full Text View - ClinicalTrials.gov.” https://clinicaltrials.gov/ct2/show/NCT04510038 (accessed Aug. 20, 2021).

“Colchicine to Reduce Cardiac Injury in COVID-19 (COLHEART-19) - Full Text View - ClinicalTrials.gov.” https://clinicaltrials.gov/ct2/show/NCT04355143 (accessed Aug. 20, 2021).

N. Mewton et al., “Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction,” Circulation, pp. 859–869, Sep. 2021, doi: 10.1161/CIRCULATIONAHA.121.056177.

B. Shah et al., “U . S . Department of Veterans Affairs,” vol. 13, no. 4, 2021, doi: 10.1161/CIRCINTERVENTIONS.119.008717.Effects.

B. Dasgeb, D. Kornreich, K. McGuinn, L. Okon, I. Brownell, and D. L. Sackett, “Colchicine: an ancient drug with novel applications B.,” Br J Dermatol, vol. 178, no. 2, pp. 350–356, 2018, doi: 10.1111/bjd.15896.

S. Stewart, K. C. K. Yang, K. Atkins, N. Dalbeth, and P. C. Robinson, “Adverse events during oral colchicine use: A systematic review and meta-analysis of randomised controlled trials,” Arthritis Res. Ther., vol. 22, no. 1, 2020, doi: 10.1186/s13075-020-2120-7.

H. Satiş et al., “Colchicine intolerance in FMF patients and primary obstacles for optimal dosing,” Turkish J. Med. Sci., vol. 50, no. 5, p. 1337, 2020, doi: 10.3906/SAG-2001-261.

E. Ben-Chetrit, “Colchicine,” Textb. Autoinflammation, p. 729, 2019, doi: 10.1007/978-3-319-98605-0_40.

D. C. Tong et al., “Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial,” Circulation, vol. 142, no. 20, pp. 1890–1900, Nov. 2020, doi: 10.1161/CIRCULATIONAHA.120.050771.

A. Slobodnick, B. Shah, S. Krasnokutsky, and M. H. Pillinger, “Update on colchicine, 2017,” Rheumatology (Oxford)., vol. 57, no. 1, pp. i4–i11, 2018, doi: 10.1093/rheumatology/kex453.

J. Dupuis et al., “Colchicine reduces lung injury in experimental acute respiratory distress syndrome,” PLoS One, vol. 15, no. 12 December, pp. 1–15, 2020, doi: 10.1371/journal.pone.0242318.

R. Ozdemir et al., “Colchicine Protects against Hyperoxic Lung Injury in Neonatal Rats,” Neonatology, vol. 102, no. 4, pp. 265–269, Nov. 2012, doi: 10.1159/000341424.

T. Sandhu, A. Tieng, S. Chilimuri, and G. Franchin, “A case control study to evaluate the impact of colchicine on patients admitted to the hospital with moderate to severe covid-19 infection,” Can. J. Infect. Dis. Med. Microbiol., vol. 2020, 2020, doi: 10.1155/2020/8865954.




DOI: http://doi.org/10.11591/ijphs.v11i4.21837

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