Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, immune-related adverse events (irAEs) increase morbidity and mortality and thereby limit therapeutic utility. The real-world incidence of the entire spectrum of pulmonary irAEs has not been systematic...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Innovative Healthcare Institute
2023-11-01
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| Series: | Journal of Immunotherapy and Precision Oncology |
| Subjects: | |
| Online Access: | https://jipo.org/doi/pdf/10.36401/JIPO-22-38 |
| _version_ | 1797402900953038848 |
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| author | Ugochi Ebinama Ajay Sheshadri Kartik Anand Iyer Swaminathan |
| author_facet | Ugochi Ebinama Ajay Sheshadri Kartik Anand Iyer Swaminathan |
| author_sort | Ugochi Ebinama |
| collection | DOAJ |
| description | Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, immune-related adverse events (irAEs) increase morbidity and mortality and thereby limit therapeutic utility. The real-world incidence of the entire spectrum of pulmonary irAEs has not been systematically described. The objective of this study is to assess the risk of developing pulmonary irAEs (pneumonitis, pleural events [i.e., effusion and pleurisy], exacerbations of airway disease [i.e., bronchitis and bronchiectasis], and sarcoidosis) with exposure to five commonly used ICIs: nivolumab, pembrolizumab, durvalumab, avelumab, and atezolizumab.
Methods: We conducted a retrospective review of the Food and Drug Administration Adverse Events Reporting System (FAERS) pharmacovigilance database. We collected data from 2012 to 2021 to assess the risk of pulmonary irAEs and performed a disproportionality analysis using Open-Vigil, a software package used for analysis of pharmacovigilance data, to calculate reporting odds ratios (RORs). We used 95% CIs to evaluate the precision of RORs. An ROR greater than 1 and the upper limit of the 95% CI indicated statistical significance.
Results: A total of 17,273,403 events were reported in FAERS between 2012 and 2021. Of these, 88,099 (0.5%) were attributed to the PD-1 (programmed cell death protein 1) inhibitors and 21,905 (0.1%) to PD-L1 (programmed death ligand 1) inhibitors of interest. The most common indication for using the ICIs of interest was lung cancer: a total of 2832 (46.70%) for the PD-1 inhibitors and 1311 (70.9%) for the PD-L1 inhibitors. In the anti–PD-1 group, 2342 (38.6%) patients were hospitalized, and 1962 (32.4%) patients died from the lung adverse event. In the PD-L1 group, 744 (40.3%) patients were hospitalized, and 520 (28.1%) patients died from the event. Nivolumab resulted in the highest statistically significant risk (ROR, 10.5; 95% CI, 10.1–10.9) for pneumonitis. Avelumab had a lesser risk for pneumonitis (ROR, 0.2; 95% CI, 0.2–0.3). The risk for pleural events was highest with nivolumab (ROR, 3.6; 95% CI, 3.4–3.9), followed by pembrolizumab (ROR, 1.8; 95% CI; 1.6–2.0) (p < 0.001), with the lowest risks from durvalumab, atezolizumab, and avelumab. For ICI-related sarcoidosis, the risk was most significant with pembrolizumab (ROR, 3.6; 95% CI, 2.8–4.7), followed by nivolumab (ROR, 2.5; 95% CI, 1.9–3.5) (p < 0.001). The RORs for all five ICIs were less than 1 for exacerbations of airway diseases as compared with other drugs.
Conclusion: Using a pharmacovigilance database, we found an increased risk of multiple pulmonary irAEs after ICI therapy, particularly with PD-1 inhibitors. Further work is needed to investigate the incidence of pulmonary irAEs other than pneumonitis. |
| first_indexed | 2024-03-09T02:30:49Z |
| format | Article |
| id | doaj.art-a8dff872e3cf4598b58a326886a8dcb3 |
| institution | Directory Open Access Journal |
| issn | 2666-2345 2590-017X |
| language | English |
| last_indexed | 2024-03-09T02:30:49Z |
| publishDate | 2023-11-01 |
| publisher | Innovative Healthcare Institute |
| record_format | Article |
| series | Journal of Immunotherapy and Precision Oncology |
| spelling | doaj.art-a8dff872e3cf4598b58a326886a8dcb32023-12-06T13:55:27ZengInnovative Healthcare InstituteJournal of Immunotherapy and Precision Oncology2666-23452590-017X2023-11-016417718410.36401/JIPO-22-38i2590-017X-6-4-177Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of PharmacovigilanceUgochi Ebinama0Ajay Sheshadri1Kartik Anand2Iyer Swaminathan31 Department of Internal Medicine, The University of Texas Health Sciences Center at Houston, McGovern Medical School, Houston, TX, USA2 Department of Pulmonary Medicine, Division of Internal Medicine, Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA3 Callahan Cancer Center, Great Plains Health, North Platte, NE, USA5 Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USAIntroduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, immune-related adverse events (irAEs) increase morbidity and mortality and thereby limit therapeutic utility. The real-world incidence of the entire spectrum of pulmonary irAEs has not been systematically described. The objective of this study is to assess the risk of developing pulmonary irAEs (pneumonitis, pleural events [i.e., effusion and pleurisy], exacerbations of airway disease [i.e., bronchitis and bronchiectasis], and sarcoidosis) with exposure to five commonly used ICIs: nivolumab, pembrolizumab, durvalumab, avelumab, and atezolizumab. Methods: We conducted a retrospective review of the Food and Drug Administration Adverse Events Reporting System (FAERS) pharmacovigilance database. We collected data from 2012 to 2021 to assess the risk of pulmonary irAEs and performed a disproportionality analysis using Open-Vigil, a software package used for analysis of pharmacovigilance data, to calculate reporting odds ratios (RORs). We used 95% CIs to evaluate the precision of RORs. An ROR greater than 1 and the upper limit of the 95% CI indicated statistical significance. Results: A total of 17,273,403 events were reported in FAERS between 2012 and 2021. Of these, 88,099 (0.5%) were attributed to the PD-1 (programmed cell death protein 1) inhibitors and 21,905 (0.1%) to PD-L1 (programmed death ligand 1) inhibitors of interest. The most common indication for using the ICIs of interest was lung cancer: a total of 2832 (46.70%) for the PD-1 inhibitors and 1311 (70.9%) for the PD-L1 inhibitors. In the anti–PD-1 group, 2342 (38.6%) patients were hospitalized, and 1962 (32.4%) patients died from the lung adverse event. In the PD-L1 group, 744 (40.3%) patients were hospitalized, and 520 (28.1%) patients died from the event. Nivolumab resulted in the highest statistically significant risk (ROR, 10.5; 95% CI, 10.1–10.9) for pneumonitis. Avelumab had a lesser risk for pneumonitis (ROR, 0.2; 95% CI, 0.2–0.3). The risk for pleural events was highest with nivolumab (ROR, 3.6; 95% CI, 3.4–3.9), followed by pembrolizumab (ROR, 1.8; 95% CI; 1.6–2.0) (p < 0.001), with the lowest risks from durvalumab, atezolizumab, and avelumab. For ICI-related sarcoidosis, the risk was most significant with pembrolizumab (ROR, 3.6; 95% CI, 2.8–4.7), followed by nivolumab (ROR, 2.5; 95% CI, 1.9–3.5) (p < 0.001). The RORs for all five ICIs were less than 1 for exacerbations of airway diseases as compared with other drugs. Conclusion: Using a pharmacovigilance database, we found an increased risk of multiple pulmonary irAEs after ICI therapy, particularly with PD-1 inhibitors. Further work is needed to investigate the incidence of pulmonary irAEs other than pneumonitis.https://jipo.org/doi/pdf/10.36401/JIPO-22-38rorpd-1pd-l1adverse events |
| spellingShingle | Ugochi Ebinama Ajay Sheshadri Kartik Anand Iyer Swaminathan Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance Journal of Immunotherapy and Precision Oncology ror pd-1 pd-l1 adverse events |
| title | Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance |
| title_full | Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance |
| title_fullStr | Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance |
| title_full_unstemmed | Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance |
| title_short | Pulmonary Immune-Related Adverse Events of PD-1 Versus PD-L1 Checkpoint Inhibitors: A Retrospective Review of Pharmacovigilance |
| title_sort | pulmonary immune related adverse events of pd 1 versus pd l1 checkpoint inhibitors a retrospective review of pharmacovigilance |
| topic | ror pd-1 pd-l1 adverse events |
| url | https://jipo.org/doi/pdf/10.36401/JIPO-22-38 |
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