Background and Aims

The increasing use of immune checkpoint inhibitors (ICIs) for curing cancer results in a wide range of novel immune related adverse events (irAEs). Among them, myositis is a rare but potentially life-threatening event.

This study aimed at investigating the risk of ICI-related myositis in real-life settingby performing a disproportionality analysis in a global pharmacovigilance database.

Methods

We conducted a case/non-case analysis using VigiBase, the WHO’s adverse drug reactions (ADRs) database, to assess myositis reporting associated with anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, avelumab, durvalumab), anti-CTLA-4 (ipilimumab, tremelimumab). Cases were defined using selected MedDRA Low Level Terms corresponding to myositis and non-cases were all other ADR. Disproportionality analysis were performed using logistic regression models to calculate Reporting Odds Ratios (ROR).

Results

A total of 14,786,263ADR were reported from January 2008 to February 2019. We identified 54,085 ICI-related ADR among which 345 myositis. ICI-related myositis was considered serious in 95% of cases, with fatal outcome in more than 20%. Association with myocarditis and myasthenia gravis was reported in 11,3% and 11,9% of cases respectively. Myositis was more than seventeen times more reported with ICI agents than with all other drugs (ROR=17.3; 95%CI:15.5–19.2). ICI-related myositis reporting was increased with anti-PD-(L)1 compared to anti-CTLA-4 agents (ROR=2.4; 95%CI:1.6–3.5), and in the group receiving combination-therapy compared to monotherapy (ROR 1.8; 95%CI: 1.3–2.4).

Conclusions

Such a strong pharmacovigilance signal suggests an increased risk of myositis under ICIs, even more increased under anti-PD(L)1 agents. Subsequent studies are required to better characterize clinical features of ICI-related myositis.