The efficacy and safety of monoclonal antibody treatments against COVID-19: A systematic review and meta-analysis of randomized clinical trials

Objectives: The use of monoclonal antibody for COVID-19 showed conflicting results in prior studies and its efficacy remains unclear. We aimed to comprehensively determine the efficacy and safety profile of monoclonal antibodies in COVID-19 patients. Methods: Sixteen RCTs were analyzed using RevMan 5.4 to measure the pooled estimates of risk ratios (RRs) and standardized mean differences (SMDs) with 95% CIs. Results: The pooled effect of monoclonal antibodies demonstrated mortality risk reduction (RR=0.89 (95%CI 0.82-0.96), I2=13%, fixed-effect). Individually, tocilizumab reduced mortality risk in severe to critical disease (RR=0.90 (95%CI 0.83-0.97), I2=12%, fixed-effect)) and lowered mechanical ventilation requirements (RR=0.76 (95%CI 0.62-0.94), I2=42%, random-effects). Moreover, it facilitated hospital discharge (RR=1.07 (95%CI 1.00-1.14), I2=60%, random-effects). Meanwhile, bamlanivimab-etesevimab and REGN-COV2 decrease viral load ((SMD=-0.33 (95%CI -0.59 to -0.08); (SMD=-3.39 (95%CI -3.82 to -2.97)). Interestingly, monoclonal antibodies did not improve hospital discharge at day 28-30 (RR=1.05 (95%CI 0.99-1.12), I2=71%, random-effects) and they displayed similar safety profile with placebo/standard therapy (RR=1.04 (95%CI 0.76-1.43), I2=54%, random-effects). Conclusion: Tocilizumab improved hospital discharge and reduced mortality as well as the need for mechanical ventilation, while bamlanivimab-etesevimab and REGN-COV2 reduced viral load in mild to moderate outpatients. In general, monoclonal antibodies are safe and should be considered in severe to critical COVID-19 patients.

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Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms

10.1101/2020.03.12.988808 ◽

2020 ◽

Author(s):

Adam McNee ◽

Trevor Smith ◽

Barbara Holzer ◽

Becky Clark ◽

Emily Bessell ◽

...

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

Viral Load ◽

Influenza Virus Infection ◽

Small Animal ◽

H1n1 Influenza ◽

Lung Pathology ◽

Host Animal ◽

Viral Shedding ◽

Robust Model

AbstractMonoclonal antibodies are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies. We show that a strongly neutralizing monoclonal antibody (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid encoded version of 2-12C, reduced pathology and viral load in the lungs, but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate monoclonal antibodies and emerging delivery platforms prior to human trials.

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Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease: a systematic review & meta-analysis

BMC Cancer ◽

10.1186/s12885-021-07889-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Muhammad Khan ◽

Zhihong Zhao ◽

Sumbal Arooj ◽

Guixiang Liao

Keyword(s):

Systematic Review ◽

Monoclonal Antibody ◽

Random Effects ◽

Metastatic Disease ◽

Radiation Necrosis ◽

Meta Analysis ◽

Cochrane Library ◽

Random Effects Model ◽

Efficacy And Safety ◽

Radiographic Response

Abstract Background Radiotherapy is the mainstay of brain metastasis (BM) management. Radiation necrosis (RN) is a serious complication of radiotherapy. Bevacizumab (BV), an anti-vascular endothelial growth factor monoclonal antibody, has been increasingly used for RN treatment. We systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab for treatment of RN in BM patients. Materials and methods PubMed, Medline, EMBASE, and Cochrane library were searched with various search keywords such as “bevacizumab” OR “anti-VEGF monoclonal antibody” AND “radiation necrosis” OR “radiation-induced brain necrosis” OR “RN” OR “RBN” AND “Brain metastases” OR “BM” until 1st Aug 2020. Studies reporting the efficacy and safety of BV treatment for BM patients with RN were retrieved. Study selection and data extraction were carried out by independent investigators. Open Meta Analyst software was used as a random effects model for meta-analysis to obtain mean reduction rates. Results Two prospective, seven retrospective, and three case report studies involving 89 patients with RN treated with BV were included in this systematic review and meta-analysis. In total, 83 (93%) patients had a recorded radiographic response to BV therapy, and six (6.7%) had experienced progressive disease. Seven studies (n = 73) reported mean volume reductions on gadolinium-enhanced T1 (mean: 47.03%, +/− 24.4) and T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI images (mean: 61.9%, +/− 23.3). Pooling together the T1 and T2 MRI reduction rates by random effects model revealed a mean of 48.58 (95% CI: 38.32–58.85) for T1 reduction rate and 62.017 (95% CI: 52.235–71.799) for T2W imaging studies. Eighty-five patients presented with neurological symptoms. After BV treatment, nine (10%) had stable symptoms, 39 (48%) had improved, and 34 (40%) patients had complete resolution of their symptoms. Individual patient data was available for 54 patients. Dexamethasone discontinuation or reduction in dosage was observed in 30 (97%) of 31 patients who had recorded dosage before and after BV treatment. Side effects were mild. Conclusions Bevacizumab presents a promising treatment strategy for patients with RN and brain metastatic disease. Radiographic response and clinical improvement was observed without any serious adverse events. Further class I evidence would be required to establish a bevacizumab recommendation in this group of patients.

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Efficacy and Safety of N-acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review & Meta-analysis

Pain Medicine ◽

10.1093/pm/pnab042 ◽

2021 ◽

Author(s):

Mohammed Mohiuddin ◽

Bianca Pivetta ◽

Ian Gilron ◽

James S Khan

Keyword(s):

Chronic Pain ◽

Sensitivity Analysis ◽

Random Effects ◽

Comparative Studies ◽

Meta Analysis ◽

Fixed Effect Model ◽

Fixed Effect ◽

Risk Of Bias ◽

Efficacy And Safety ◽

Effect Model

Abstract Objective To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain. Methods A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of Bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis. Results Nine studies (n = 863) were included (5 randomized controlled trials [RCTs], 2 open-label non-comparative studies and 2 comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of 3 RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% CI -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain. Conclusions While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine’s role, if any, in pain medicine.

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