Risk of Ophthalmic Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis

ABSTRACT

Background

Immune checkpoint inhibitors (ICIs) -induced adverse events (AEs) have been reported affecting almost all human organs. However, studies about ocular AEs are few. A meta-analysis was performed to evaluate the risks of ICI-related ophthalmic AEs compare to chemotherapy.

Methods: Eligible studies were selected from phase II/III randomized controlled trials investigating ICIs. The data were analyzed by R software and Stata.

Results

Odds ratio of treatment-related AE (trAEs) and nonspecific ophthalmic trAEs (NS-trAEs) were lower for PD-1/PD-L1 inhibitors than chemotherapy (OR 0.44, p < .05; OR 0.28, p < .001; OR 0.18, p < . 05; OR: 0.18, p < .001respectively). Compared with monotherapy, PD-1 plus CTLA-4 inhibitors increased the risks of immune-related AEs (irAEs) (OR 4.52, p < .01); ICIs plus chemotherapy increased the risks of trAEs and irAEs (OR 2.82, p < .001; OR 3.63, p < .05 respectively).

Conclusions

PD-L1/PD-1 inhibitors had lower risks of trAEs and NS-trAEs than chemotherapy; Compared with monotherapy, combination therapy had higher risks of ophthalmic trAEs and irAEs.

Abbreviation

PD-1: programmed cell death protein 1; PD-L1: programmed cell death protein ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; ICI: immune checkpoint inhibitor; AE: adverse event; trAE: treatment-related adverse event;irAE: immune-related adverse events; NS-trAE: nonspecific ophthalmic treatment-related adverse event; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; ORR: objective response rate; MM: melanoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; HNSCC: head-neck squamous cell carcinoma; PICOL: patient, intervention, comparison, and outcome; Versus: VS; Chem: chemotherapy; 95%CI: 95% confidence interval; FEM: fixed-effects model; REM: random-effects model; NA: not applicable; MeSH: medical subject heading

KEYWORDS:

• Treatment-related adverse events
• immune-related adverse events
• ophthalmic
• immune checkpoint inhibitors
• meta-analysis

Authors’ contributions

Y.L.H. and D.Y.W. have access to all the data included in the study. They are responsible for the completeness of the data and the accuracy of our analysis. Q.S. and H.Y.L. helped to design the study. Q.S., W.W., R.Y.T., and Y.L.H. contributed to the statistical analysis and the revision of this manuscript. Q.S. and H.Y.L. approved the final manuscript.

Acknowledgments

The working group wishes to thank Yang-Tian, LU (College Jean-de-Brebeuf, Montreal, Quebec, Canada) for their assistance in the preparation and review of this manuscript.

Availability of data and material

Firstly, all of the datasets used in our manuscript are available in the [Pubmed or Embase] repository, [https://www. ncbi.nlm.nih.gov/

Pubmed/and http://www.embase.com/search] (See Supplementary Table S1: search performed in Pubmed and Embase).

Secondly, the datasets analyzed in our manuscript are available according to our methods part or from the corresponding author on reasonable request.

Declaration of interest

The authors declare no competing interests in preparing this article.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This research is supported by the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education [Grant No. KZ202010025047] and the National Natural Science Foundation of China [Grant No. 92046015].