The safety population included 663 of the 666 patients enrolled in the study across 26 hospitals in China. Three patients were excluded from the safety population because the data to confirm whether they had received at least one dose of ixekizumab were not available.

A total of 75/663 (11.3%) patients discontinued from the study after 12 weeks. The most common reasons for discontinuation were patient decision (35 patients, 5.3%), loss to follow-up (19 patients, 2.9%), and poor compliance (11 patients, 1.7%). Five patients discontinued due to an AE; the events included pustular psoriasis, dermatitis atopic, erythema, psoriasis, oedema, hypersensitivity, and hypoproteinemia (Note that > 1 AE could lead to discontinuation in a single patient) [12].

More than one-half of the patients (55.4%) were using ≥ 1 concomitant medication. The most commonly received concomitant medications were dermatologicals (35.0%) at an anatomical level. The dermatologicals used by at least 10% of the population were emollients and protectives (14.0%), corticosteroids, dermatological preparations (12.2%), and antipruritics, including antihistamines and anesthetics (11.6%).

A summary of AESIs is shown in Table 1. At least one AESI was reported in 224 (33.8%) patients, and in 181 (27.3%) patients AESIs were considered related to ixekizumab. The most commonly reported AESI was ISRs (131 patients, 19.8%). No MACE or cases of interstitial lung disease were reported. One case of lung neoplasm (causality was determined as “no”) and one case of ulcerative colitis (causality was determined as “yes”) was reported. The three AESIs reported by the highest proportions of patients in addition to hepatic events are detailed below.

In total, 131 (19.8%) patients reported 349 ISRs, 335 (96.0%) of which were mild; no severe or serious events were reported. The most commonly reported ISRs were erythema (64 patients, 9.7%), swelling (62 patients, 9.4%), and pain (31 patients, 4.7%). It should be noted that patients may have experienced multiple ISRs that were recorded as separate events.

In total, 80 patients (12.1%) reported 92 infections. Most infections were mild in intensity (80 of 92 events, 87.0%); no severe infection or SAE of infection was reported. Infections reported in > 1% of patients were upper respiratory tract infection (23 patients, 3.5%), nasopharyngitis (12 patients, 1.8%), pharyngitis (8 patients, 1.2%), and tinea pedis (8 patients, 1.2%). Two patients reported herpes simplex and herpes virus infection separately. No patient reported an opportunistic infection in a narrow search. No cases of TB, HBV infection, or candidiasis were reported.

There were 70 allergic reactions/hypersensitivity events reported in 59 (8.9%) patients, all of which were considered not potentially anaphylactic in nature. The majority of nonanaphylactic allergic reactions/hypersensitivity events were mild (58 of 70 events, 82.9%), occurring in 48 (81.4%) patients, with no severe events reported. One patient had moderate hypersensitivity, which was classified as an SAE (considered medically significant). Events reported by > 1% of patients were urticaria (22 patients, 3.3%), dermatitis (12 patients, 1.8%), hypersensitivity (8 patients, 1.2%), and eczema (7 patients, 1.1%).

All six hepatic events reported in six patients (0.9%) were mild in intensity. Abnormal liver function test results were reported in three patients, and three patients had conditions related to liver damage (hepatic steatosis or liver disorder). eDISH illustrated that most patients had liver function test results within the normal range and no patient had results that met Hy’s law (Fig. 1).

Evaluation of drug-induced serious hepatotoxicity (eDISH) with ixekizumab. ALT alanine aminotransferase, Ixe ixekizumab, TBIL total bilirubin, ULN upper limit of normal.

No significant differences in the incidence of AEs or AEs considered related to study drug by the investigators were observed over 12 weeks across the majority of the subgroups analyzed including age and weight, with the exception of sex and number of ixekizumab injections after baseline (Table 2). A higher proportion of female patients had at least one AE over 12 weeks compared with male patients (99/186, 53.2% versus 184/477, 38.6%, p = 0.0006). The proportion of patients with at least one AE increased with an increasing number of ixekizumab injections after baseline [61/188 (32.4%) of those who received zero to one injection, 151/338 (44.7%) for two to four injections, and 61/106 (57.5%) for five to seven injections; p = 0.0001].

Only data for the most common AESIs (ISRs, infections, and allergic reaction/hypersensitivity) were analyzed by subgroup (Table 3) due to small numbers of patients (n ≤ 10) for the other AESIs.

ISRs A higher proportion of female patients than male patients had ISRs [47/186 (25.3%) versus 84/477 (17.6%); p = 0.0261]. In addition, the proportions of patients with ISRs increased as the number of ixekizumab injections increased. ISRs were reported in 23/188 (12.2%) patients who received zero to one ixekizumab injections, 67/338 (19.8%) who received two to four injections, and 36/106 (34.0%) who received five to seven ixekizumab injections (p < 0.0001). No significant differences were observed over 12 weeks in patients who reported ISRs across the other subgroups analyzed.

Infections The proportions of patients with infections increased as the number of ixekizumab injections increased. Infections were reported in 14/188 (7.4%) patients who received zero to one ixekizumab injections, 46/338 (13.6%) who received two to four injections, and 18/106 (17.0%) who received five to seven injections (p = 0.0338). In addition, a higher proportion of patients with a history of allergic reactions/hypersensitivity had an infection (8/23, 34.8%) compared with those without a history of allergic reactions/hypersensitivity (72/640, 11.3%; p = 0.0034). No significant differences were observed across the other subgroups analyzed.

Allergic reactions/hypersensitivity events A higher proportion of female patients than male patients had allergic reactions/hypersensitivity events [26/186 (14.0%) versus 33/477 (6.9%); p = 0.0041]. There were no significant differences across the other subgroups analyzed. Patient’s history of allergic reaction/hypersensitivity was not significantly correlated with the occurrence of allergic reactions AESI (p = 0.1394).