Comparative Risks of Pneumonitis amongst Immune Checkpoint Inhibitors in patients with Lung Cancer: A Network Meta-Analysis of Randomized Clinical Trials

BackgroundDespite Immune checkpoint inhibitors (ICPIs) transformation of lung cancer treatment, pneumonitis remains a potentially serious immune-related adverse event. In this review we conducted a network meta-analysis (NMA) to quantify the exact burden of pneumonitis risk across multiple ICPIs analogs.MethodsWe searched the following data bases PubMed, Embase, Scopus MEDLINE and Cochrane data base of systematic reviews as well as gray literature google scholars for eligible studies reporting on the prevalence of pneumonitis following immune check points inhibitors exposures. 29 studies enrolling 15,271 patients with non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC), analyzing both monotherapy and combination regimens satisfied inclusion criteria included in the review. Pairwise and network meta-analyses were performed to estimate pooled odds ratios (ORs) for pneumonitis, using placebo as the common comparator. Sensitivity analyses assessed the impact of study quality and combination therapies.ResultsPembrolizumab was associated with a significantly increased risk of pneumonitis compared to placebo (odds ratio [OR] = 2.67, 95% confidence interval [CI]: 1.70–4.17), with similar elevated risk observed for sugemalimab (odds ratio [OR] = 2.45, 95% confidence interval [CI]: 1.52–3.95). Nivolumab showed a nonsignificant but elevated estimate (odds Ratio [OR] = 2.69, 95% confidence interval [CI]: 0.64–11.35). Atezolizumab and ipilimumab demonstrated modest or uncertain risk. Heterogeneity was low (I² = 12%), and results were robust to sensitivity analyses. Higher pneumonitis rates were observed in combination regimens.ConclusionOur analysis demonstrates that pneumonitis risk varies among ICPIs, with pembrolizumab and sugemalimab showing the highest odds. Although the absolute incidence is low, the potential severity of pneumonitis warrants vigilant monitoring. These results should guide clinicians in risk stratification, treatment planning, and support t