A meta-analysis of real-world studies of COVID-19 in patients with autoimmune diseases is needed. Conclusion This meta-analysis showed that IL-12/23 or IL-23 antagonists had an increased risk of URTIs, but not viral URTIs, LRTIs including infectious pneumonia, and noninfectious ILD. Footnotes Funding sources: None. Conflicts of interest: None disclosed. IRB approval status: Not applicable. Reprints not available from the authors.. RTIs (Mantel-Haenszel risk difference, 0.019; 95% confidence interval, 0.005-0.033; statistic. An value of less than 25% indicated low heterogeneity, 25% to 75% indicated moderate heterogeneity, and greater than 75% indicated considerable heterogeneity.29 Heterogeneity was evaluated by using the Cochran statistic with a significance level of value of .05 for significance. Results Study characteristics We identified 21,102 citations through the literature search, excluded 21,030 titles and abstracts after the initial screening, and assessed 72 studies for eligibility. A final number of 43 full-text articles and 2 studies registered only in ClinicalTrials.gov met?all eligibility criteria and included 54 RCTs with a total of 10,907 patients with antiCIL-12/IL-23 or antiCIL-23 antibodies and 5175 with placebo (Fig 1). The 54 RCTs included 1 RRx-001 study of brazikumab (59 patients), 8 of briakinumab (1817 patients), 9 of guselkumab (1321 patients), 5 of risankizumab (830), 5 of tildrakizumab (1596 patients), and 26 of ustekinumab (5284 patients). All of the included studies are randomized, double-blind, placebo-controlled studies and have high scores in the Jadad scoring system. The characteristics and outcomes of the included studies are summarized in Table I .33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 The mean ages of RRx-001 patients and percentages of male patients were 43.8?years and?66.6% for guselkumab, 42.8?years and 65.4% for risankizumab, 37.6?years and 62.4% for tildrakizumab, 43.3?years and 49.5% for briakinumab, and 43.3?years and 54.0% for ustekinumab. The percentages of studies that permitted use of concomitant drugs (eg,?corticosteroids, budesonide, thiopurines, methotrexate, calcineurin inhibitors, or aminosalicylates) during the trials were 40.0% for risankizumab, 38.5% for ustekinumab, 37.5% RHOC for briakinumab, 0% for guselkumab, and 0% for tildrakizumab. As for brazikumab, 1 study for CD was included in this analysis and permitted concomitant drugs (Table I). Table I Characteristics of randomized controlled trials of IL-12/23 or IL-23 antagonists? and 5, and viral pneumonia were not reported. The overall risk of?infectious pneumonia was not significantly increased in the treatment group compared to placebo (MH RD, 0; 95% CI, -0.002 to 0.002; and species.70 Meanwhile, IL-23 maintains IL-17Cproducing Th17?cells, and the deficiency of IL-17 immunity results in infections of species.71 , 72 Our results showed that IL-12/23 or IL-23 antagonists did not increase the risk of LRTIs and infectious pneumonia, including or any virus. As for viral RTIs, previous studies showed that IL-17Cknockout mice had lower levels of lung inflammation by influenza virus compared with the wild type.73 A study of the Middle East respiratory syndrome coronavirus showed that a patient with a poor outcome had an increased level of IL-17 expression in the lung.69 These data suggest that IL-12/23 or IL-23 inhibitors might theoretically be preventive for severe acute respiratory syndrome coronavirus 2Cinduced pneumonia rather than detrimental in autoimmune diseases during the COVID-19 pandemic. RRx-001 Limitations First, this study did not assess the long-term effect of IL-12/23 or IL-23 antagonists on RTIs and ILD. However, 92.6% (50/54) of the included studies reported RTIs during placebo-controlled phases. The FDA reported whether the onset of ILD was acute or subacute,14 so our data would most likely include the incidence of these events. Second, regarding infectious pneumonia and ILD, many studies had zero events in both arms (87% [47/54] and 94% [51/54], respectively). Thus, we undertook comprehensive analyses that either included or excluded double-zero-event studies. The analysis with 0.5 constant correction showed a lower risk of these events in the treatment group. We also used treatment arm correction because this method performed better than 0.5 constant correction to examine rare events.74 Third, our study may not reflect the risk in patients at high risk for RTIs because of the possible exclusion of patients with recent RTIs or chronic lung disease in clinical trials. Fourth, we categorized RTIs into URTIs, viral URTIs, and LRTIs based on MedDRA, which is widely used?in clinical trials, but not so much in clinical research. Furthermore, the included studies were conducted before the.