Arthralgia in patients with cancer receiving immune checkpoint inhibitor: A systematic review and meta-analysis.
Authors: Yoshito Nishimura, Jonathan Estaris, Mako Koseki, Evelyn Elias, Fnu Chesta, Kensuke Takaoka, Theresa Shao, Yu Fujiwara
Journal: Journal of Clinical Oncology (2024)

e14601 Background: Immune checkpoint inhibitors (ICIs) have become an integral part of the standard therapeutic approaches for patients with cancer. However, the occurrence of immune-related adverse events (irAEs) occasionally poses challenges to quality of life (QoL). Despite the utility of ICIs in a daily practice, evidence about the frequency of arthralgia associated with ICIs, which severely affects QoL of patients with cancer, is limited. The study aimed to evaluate the incidence and treatment outcomes of arthralgia associated with ICIs. Methods: We performed a database search in PubMed/Medline, Embase, and Web of Science for phase 3 randomized control trials (RCTs) evaluating ICI therapy and reporting the incidence of arthralgia. The incidence of arthralgia was calculated in patients with solid tumors treated with ICIs. We performed a random-effect model meta-analysis to pooled odds ratios (ORs) of these outcomes using RCTs evaluating 1) the combination of ICIs with systemic therapy versus systemic therapy alone, 2) ICI vs chemotherapy (taxanes, non-taxanes, and mixed chemotherapeutic regimens) to assess the effect of ICIs on the incidence of arthralgia. I 2 statistics was used to assess heterogeneity among the included studies and subgroups with I 2 higher than 50% being considered high heterogeneity. Results: A systematic review identified 40 RCTs to analyze the incidence of arthralgia. The incidence of any-grade treatment-related arthralgia was 12.0% (n=1125/9395), and that of grade 3–5 treatment-related arthralgia was 0.54% (n = 47/8723). The addition of ICIs was associated with an increase in both any-grade (OR 1.32, 95% CI: 1.13–1.54, p = 0.001) and grade 3-5 arthralgia (OR 1.78, 95% CI: 1.08-2.94, p = 0.02: subgroup differences by ICB subtype: I 2 = 0%). Subgroup analysis revealed that the addition of ICIs to cytotoxic chemotherapy was associated with an increase in the incidence of any-grade arthralgia (OR 1.35, 95% CI: 1.05–1.73, p = 0.02. The meta-analysis of ICI versus chemotherapy found that the incidence of arthralgia remained significantly increased when ICIs were compared with non-taxane chemotherapy (OR 6.83, 95% CI: 3.05–15.30, p &lt; 0.00001), but not with taxanes (OR 0.74, 95% CI: 0.44–1.24, p = 0.25, I 2 = 67%). Conclusions: Although the incidence of grade 3–5 arthralgia seems low, we revealed that the addition of ICIs to systemic therapy increased both any-grade and grade 3-5 arthralgia. Additionally, the incidence of any-grade arthralgia was more observed with ICIs than with non-taxane chemotherapy. In contrast, the incidence of arthralgia was not significantly different between ICIs and taxanes or mixed chemotherapy. The findings may be useful for patient education receiving ICIs for solid tumors. Future prospective studies are warranted to evaluate the therapeutic approach to grade 3–5 arthralgia and the need for ICI discontinuation.