3.5.1. TEAEs

Twelve studies (involving 3402 patients) were included in the analysis of TEAEs. AD patients treated with JAK inhibitors had relatively higher risks of developing TEAEs (RR = 1.14; 95% CI = 1.02–1.28) than those treated with placebo (Table 2). Most TEAEs were tolerable; nasopharyngitis was the most reported event (Table 3), followed by upper respiratory tract infection, headache, nausea, diarrhea, elevated blood creatine phosphokinase levels, and acne. Herpesvirus infection was reported in patients treated with abrocitinib or baricitinib. However, substantial heterogeneity was observed among studies (I<sup>2</sup> = 52%; *P* = 0.023). Table 2 shows several potential effect modifiers accounting for the considerable heterogeneity among the TEAEs, including administration route, AD severity, and treatment duration. Patients who were administered oral JAK inhibitors experienced moderate

to severe AD at baseline. Those treated with JAK inhibitors for >12 weeks were more likely to develop TEAEs.

#### 3.5.2. AEs Leading to Drug Discontinuation

Fourteen studies (involving 3926 patients) were included in the analysis of AEs that led to drug discontinuation. Table 2 shows that patients who were administered with JAK inhibitors were unlikely to have higher risks of developing AEs (RR = 0.89; 95% CI = 0.57–1.38) than those treated with placebo. No significant heterogeneity was detected (I<sup>2</sup> = 0%; *P* = 0.62).
