reported injection-site reactions. Consistent with the 12-week induction period of the UNCOVER studies, the most common injection-site reactions across all 11 studies were classified as nonspecified (9.5%), erythema (3.1%), and pain (1.7%). After the first 2 weeks of treatment, the frequency of injection-site reactions decreased and then remained stable (≤4.2%) out to week 156 (Figure 3). A similar pattern was reported for pain and erythema. The incidence of injection-site pain was stable at 0.1% and injection-site erythema remained below 0.3% from week 36 to week 156.There were no serious adverse events related to injection-site reactions.Relationship Between Injection-Site Reaction, Previous Exposure to Biologic Agents, Race, and Development of ADAOf the 1167 patients treated with IXE Q2W in the 12-week induction period of the UNCOVER studies, 13.7% of those who had previously used biologic therapy reported injection-site reactions relative to 18.0% of patients who had never used biologic therapy. In a subgroup analysis of injection-site reactions by race, the frequency of injection-site reactions among White, Asian, and Other races was comparable with the global population during the 12-week induction period (Figure 1). No association of injection-site reactions and TE-ADA against ixekizumab was established (Table 3).
DISCUSSION
In clinical trials demonstrating the efficacy and safety of ixekizumab as a treatment for moderate-to-severe psoriasis, injection-site reactions were among the most commonly reported adverse events. This report details the injection-site reactions reported in ixekizumab psoriasis trials to provide more comprehensive information for patients and clinicians. While injection-site reactions were not reported by all patients who received ixekizumab, it is important that patients be informed of the possibility and reported pattern of injection-site reactions.Typically, injection-site reactions were reported within the first 2 weeks of treatment. In addition, longer-term safety data, summarized by 2 week intervals through 156 weeks of treatment, demonstrate a decrease in the rate with longer durations of ixekizumab exposure. The frequencies of the injection-site reactions tapered off rapidly and over time. The reactions were generally mild-to-moderate in severity, nonserious, resolved spontaneously without concomitant treatment, and did not usually lead to treatment discontinuation. The most typically described injection-site reaction was characterized as a clearly red papule, but there were cases (13% to 15%) in which the reaction was of greater magnitude (ie, bright red [1 patient had a dark scar] or ≥2 mm papule). In subgroup analyses, no relationship between injection-site reactions and previous exposure to biologic agents, race, or development of TE-ADA were identified. Consistent with the findings that a few injection-site reactions were characterized as more remarkable, a case study reported a 47-year-old female whose injection-site reaction resulted in significant coverage and discontinuation of treatment.17 Apart from this case report, recall injection-site reactions have been reported postmarketing, although such a phenomenon was not reported during clinical trials.In general, the etiology of injection-site reactions is multifactorial and may be associated with both immunologic and non-immunologic
