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

Abstract

SummaryBackground Infections are associated with biological therapies in psoriasis. Objectives To summarize the incidence of infections in patients with moderate-tosevere 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 < 0Á05); 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 1Á3). 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.

Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive inflammation

“…A higher percentage of fungal infections, properly managed with antifungal treatments, has been reported in some trials of the blockade of IL-17-mediated immunity (e.g. anti-IL-17A or anti-IL-17RA Abs in patients with psoriasis or psoriatic arthritis) 135, 136 . Thus, fine control of balance between pathogenic and protective IL-17 immunity will be of crucial importance in the development of future therapeutic strategies for treating inflammatory and infectious diseases.…”

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors)

“…Candida infections were more frequently diagnosed in the ixekizumab group (4.8 episodes per 100 patientyears), particularly oral and vulvovaginal candidiasis. None of the cases of Candida infection (including the eight episodes of oesophageal candidiasis) required discontinuation of ixekizumab [168]. Only two patients developed non-serious VZV infection within the ixekizumab-treated group.…”

“…A pooled analysis of seven controlled and uncontrolled ixekizumab psoriasis trials, with approximately 4200 patients followed for a median of 507 days, has been recently published [168]. Although the overall rate of infection was significantly higher for ixekizumab than for the comparator during the induction (weeks 0 to 12) period of therapy (118.4 versus 100.5 episodes per 100 patient-years, respectively), the incidence of serious infections was low and similar between active treatment groups (2.4 and 1.8 episodes per 100 patient-years for ixekizumab and etanercept).…”

“…There were no cases of TB, although it should be noted that most patients were recruited from countries of low endemicity and that LTBI screening was usually mandatory. Likewise, no HBV or HCV reactivation was reported either, with most RCTs requiring screening for chronic infection before initiating the study drug [168].…”

Recomendaciones sobre el manejo de pacientes adultos con enfermedades reumáticas en el contexto de la infección por SARS-CoV-2/COVID-19. Asociación Colombiana de Reumatología

“…En los estudios de seguimiento a largo plazo de pacientes tratados para psoriasis, artritis psoriásica y espondilitis anquilosante con secukinumab se han reportado casos de infección oportunista por Candida a nivel cutáneo o de mucosas, todos casos de severidad leve a moderada, sin que a la fecha se reporten pacientes con candidiasis sistémica 69 . Resultados similares se han reportado con ixekizumab 70 . Se han reportado también casos de herpes zóster con el uso de inhibidores de IL-17, sin embargo, no se ha demostrado que este aumento sea estadísticamente significativo cuando se compara con placebo 71 .…”