A randomized clinical trial study on the efficacy and safety of adalimumab and methylprednisolone pulse therapy in the treatment of COVID-19 patients with acute respiratory distress syndrome
Omid Yazdani, Ramin Hamidi Farahani, Reza Mosaed, Amir Nezami Asl, Ebrahim Hazrati
Immunopathologia Persa, doi:10.34172/ipp.2022.30322
Introduction: Adalimumab reduces the expression of the angiotensin-converting enzyme (ACE2) receptor at the cell surface, therefore it is thought to be effective in treating patients with COVID-19. Objectives: The present study was conducted to evaluate the effectiveness of adalimumab and pulsed corticosteroids in treating patients with severe acute respiratory failure due to COVID-19. Patients and Methods: The present double-blind clinical trial study was carried out on patients with COVID-19 referred to Imam Reza hospital, Tehran. Patients were randomly divided into two groups of intervention (patients under standard treatment according to the national protocol of Iran + methylprednisolone + adalimumab) and control (patients under standard treatment according to the national protocol of Iran + methylprednisolone). Results: The patients' hospitalization information shows that the duration of patients' hospitalization in the intervention group was significantly shorter than their counterparts in the control group (P = 0.041). Serum levels of total bilirubin on the ninth day (P = 0.043) and GCS (Glasgow coma scale) on the ninth day (P = 0.041) and tenth (P = 0.039) in the adalimumab group were significantly increased compared to the control group. However, the direct bilirubin value on the eighth day (P=0.031), serum creatinine on the 8th (P = 0.047), 9th (P = 0.047) and 10th (P = 0.047) days and also PEEF (pericarditis/pericardial effusion) on the tenth day were significantly lower in the intervention group than the control group.
Conclusion: The administration of adalimumab significantly increases the GCS of COVID-19 patients and reduces the length of hospital stay. Trial Registration: This study is designed as a double-blind clinical trial (identifier: IRCT20200406046963N2, https://www.irct.ir/trial/55011 ), and has been approved by the ethics committee in biomedical research of AJA University of Medical Sciences (#IR.AJAUMS.REC.1400.
Authors' contribution
Conflicts of interest The authors declare there is no conflict of interest.
Ethical issues The present study was conducted according to the Declaration of Helsinki and with the approval of the ethics committee of AJA University of Medical Sciences. Thus, the Ethics Committee in Biomedical Research of AJA University of Medical Sciences reviewed the implementation process of this study and declared it applicable following its approved protocols (IR.AJAUMS. REC.1400.032). According to the structure defined for the study (randomized clinical trial), informed consent was obtained from all participants before the intervention, and the whole process of treatment and intervention was free in the form of research. The trial protocol was approved by the Iranian Clinical Trial Registry (identifier: IRCT20200406046963N2, https://www.irct. ir/trial/55011 ). Besides, ethical issues (including plagiarism, data fabrication, double publication) have been completely observed by the authors.
Funding/Support The present study was conducted with the financial and moral support of the Vice-Chancellor for Research and Technology of AJA University of Medical Sciences (Grant#97001405).
References
References
Bertoncelli, Guidarini, Greca, Ratti, Falcinella et al., COVID19: potential cardiovascular issues in pediatric patients, Acta Biomed,
doi:10.23750/abm.v91i2.9655Bertuzzo, Mari, Pasetto, Miccoli, Casagrandi et al., The geography of COVID-19 spread in Italy and implications for the relaxation of confinement measures, Nat Commun,
doi:10.1038/s41467-020-18050-2Clark, Vagenas, Panesar, Cope, What does tumour necrosis factor excess do to the immune system long term?, Ann Rheum Dis,
doi:10.1136/ard.2005.042523Conti, Lasagni, Bigi, Pellacani, Evolution of COVID-19 infection in four psoriatic patients treated with biological drugs, J Eur Acad Dermatol Venereol,
doi:10.1111/jdv.16587Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105938Gatto, Bertuzzo, Mari, Miccoli, Carraro et al., Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures, Proc Natl Acad Sci,
doi:10.1073/pnas.2004978117Ghormade, Kumar, Tingne, Keoliya, Distribution & diagnostic efficacy of cardiac markers CK-MB & LDH in pericardial fluid for postmortem diagnosis of ischemic heart disease, J Forensic Leg Med,
doi:10.1016/j.jflm.2014.09.011Jaffe, Landt, Parvin, Abendschein, Geltman et al., Comparative sensitivity of cardiac troponin I and lactate dehydrogenase isoenzymes for diagnosing acute myocardial infarction, Clin Chem,
doi:10.1093/clinchem/42.11.1770Kuppen, Jonges, Van De Velde, Vahrmeijer, Tollenaar et al., Liver and tumour tissue concentrations of TNF-alpha in cancer patients treated with TNF-alpha and melphalan by isolated liver perfusion, Br J Cancer,
doi:10.1038/bjc.1997.255Martins, Li, Baskin, Jialal, Keffer, Comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the late diagnosis of myocardial injury, Am J Clin Pathol,
doi:10.1093/ajcp/106.6.705Soy, Keser, Atagündüz, Tabak, Atagündüz et al., Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment, Clin Rheumatol,
doi:10.1007/s10067-020-05190-5Thalha, Lee, Besari, Omar, Have we found the panacea to COVID-19 with remdesivir, an old but newly packaged drug?, J R Coll Physicians Edinb,
doi:10.4997/JRCPE.2020.217Thienemann, Pinto, Grobbee, Boehm, Bazargani et al., World Heart Federation Briefing on Prevention: Coronavirus Disease 2019 (COVID-19) in Low-Income Countries, Glob Heart,
doi:10.5334/gh.778DOI record:
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