Infections from seven clinical trials of ixekizumab, an anti‐interleukin‐17A monoclonal antibody, in patients with moderate‐to‐severe psoriasis

• Published in: British journal of dermatology (1951) Vol. 177; no. 6; pp. 1537 - 1551
• Main Authors: Papp, K.A., Bachelez, H., Blauvelt, A., Winthrop, K.L., Romiti, R., Ohtsuki, M., Acharya, N., Braun, D.K., Mallbris, L., Zhao, F., Xu, W., Walls, C.D., Strober, B.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2017
• Subjects: Adult; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Candida; Candidiasis; Clinical trials; Cytokines; Dermatologic Agents - administration & dosage; Dermatologic Agents - adverse effects; Esophagus; Etanercept; Etanercept - administration & dosage; Etanercept - adverse effects; Female; Hepatitis; Herpes zoster; Humans; Immunotherapy; Infection - chemically induced; Infections; Male; Middle Aged; Monoclonal antibodies; Neutropenia; Psoriasis; Psoriasis - drug therapy; Randomized Controlled Trials as Topic; Sensitivity analysis; Tuberculosis
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.15723

Summary Background Infections are associated with biological therapies in psoriasis. Objectives To summarize the incidence of infections in patients with moderate‐to‐severe psoriasis treated with ixekizumab, an anti‐interleukin‐17A monoclonal antibody. Methods Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo‐controlled induction (weeks 0–12; UNCOVER‐1, UNCOVER‐2 and UNCOVER‐3) and maintenance periods (weeks 12–60; UNCOVER‐1 and UNCOVER‐2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER‐2 and UNCOVER‐3). Incidence and exposure‐adjusted incidence rates (IRs) per 100 patient‐years (PYs) are reported. Results Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0–12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer‐term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. Conclusions Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups. What's already known about this topic? Infections are associated with biological therapies in psoriasis. Interleukin (IL)‐17A plays a role in host mucocutaneous defence and inhibition of IL‐17A may increase the risk of Candida albicans infections. The overall safety of ixekizumab has been previously reported; this paper endeavours to provide more specific information about infections. What does this study add? We report the incidence of specific treatment‐emergent infections reported in a database of > 4000 patients with moderate‐to‐severe psoriasis treated with ixekizumab. This study provides detailed accounts of infection‐related adverse events categorized by special topics, including tuberculosis, Candida infections, staphylococcal infections, herpes zoster, viral hepatitis and infections preceded/accompanied by neutropenia. We performed sensitivity analyses of infection rates over time for all patients treated with ixekizumab (12‐week interval analyses up to 108 weeks and times to occurrence of infection events). Plain language summary available online Respond to this article