The Risk Ratio of Immune-Related Colitis, Hepatitis, and Pancreatitis in Patients With Solid Tumors Caused by PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

Abstract

Purpose: The meta-analysis was put into practice in evaluating the risk ratio of immune-related digestive system inflammation in patients with solid tumors caused by PD-1/PD-L1 inhibitors.Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Results: After screening and eligibility assessment, a total of 26 clinical trials involving 16,409 patients were selected for the final quantitative synthesis. Immune-related digestive system inflammations, including colitis, hepatitis, pancreatitis, were evaluated separately. Compared with chemotherapy, PD-1/PD-L1 inhibitors led to an increase in the incidence risk of all grade colitis (RR = 2.43, 95% CI: [1.23, 4.82], P = 0.01). Similar incidence trend could also be seen when PD-1/PD-L1 inhibitors were combined with chemotherapy (RR = 2.62, 95% CI: [1.25, 5.48], P = 0.01). Whether compared with Nivolumab plus Ipilimumab or Ipilimumab alone, the incidence risk of colitis in the Nivolumab group was significantly lower than that of the control group. Similar analysis results could also be seen in the incidence risk of hepatitis. We did not find a statistically significant effect on the incidence of immune-related pancreatitis after the use of PD-1/PD-L1 inhibitors.Tian et al.Inflammation and Anti-PD-1/PD-L1 Therapy Conclusion: The use of PD-1/PD-L1 inhibitors increased the incidence risk of immune-related colitis and hepatitis, but this potential to increase the incidence risk of the disease was weaker than Ipilimumab.

The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

“…The PRISMA flow diagram was shown in (Figure 1), while the bias assessment summary of all enrolled clinical trials were provided in (Supplementary Figure 1). A total of 589 published studies was found by PubMed search, while 37 studies were gotten from the former published meta-analysis (61)(62)(63). After eligibility assessment, 5 articles were only used for the systematic review (13,(20)(21)(22)(23), while 42 articles were used for the final comprehensive analysis (4-12, 14-19, 24-50).…”

Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma

“…Dual checkpoint inhibition induced by combination therapy with nivolumab and ipilimumab improves response rates in patients with metastatic melanoma compared to monotherapy. However, a higher rate of toxicity, including immune-related colitis, seems to be present under this regimen showing itself as ICI-induced diarrhea [5, 10]. Diagnostic colonoscopy and multiple colonic biopsies are necessary for the diagnosis of ICI-induced colitis, as a diversity of clinical, endoscopic and histological manifestations have been observed in patients with ICI-induced diarrhea [10].…”

“…A T cell-mediated immune response is probably involved in the ICI-induced colitis, as infiltration with CD8 + cells and T-bet expressing CD4 + cells has been observed in the colon biopsies of patients receiving nivolumab [4]. A meta-analysis by Tian et al [5] reported an increased incidence risk of all grade colitis in patients with solid tumors receiving ICIs, compared to those undergoing chemotherapy or chemotherapy and ICIs. The lower incidence risk was observed under monotherapy with nivolumab [5].…”

“…A meta-analysis by Tian et al [5] reported an increased incidence risk of all grade colitis in patients with solid tumors receiving ICIs, compared to those undergoing chemotherapy or chemotherapy and ICIs. The lower incidence risk was observed under monotherapy with nivolumab [5].…”

Advancing to the era of cancer immunotherapy

“…Despite the improved safety profile, greater attention should be given to the special irAEs of anti‐PD therapy, which can be fatal. IrAEs most commonly affect the gastrointestinal tract, endocrine glands, skin, and liver [ 302 ], but severe pneumonitis, myocarditis, colitis, hepatitis and neurological toxicities can also occur and lead to a dismal prognosis [ 303 , 304 , 305 , 306 , 307 ]. For instance, fulminant ICI‐related myocarditis has been reported to increase in occurrence with the increased use of ICIs [ 304 ].…”