Q&A: Retention, Safety of Ixekizumab in Patients with Psoriatic Arthritis

In patients with psoriatic arthritis (PsA) who were refractory to various lines of biologic and targeted synthetic drugs, ixekizumab (Taltz; Eli Lilly), an anti-interleukin (IL)-17A therapy, showed a good retention rate at 1 and 2 years, according to a study published in the Journal of Clinical Medicine.¹ Moreover,depression wasthe only comorbid factor associated with lower survival of ixekizumab, while cardiometabolic risk factors including obesity and smoking did not affect the drug survival rate.

Rubén Queiro, MD, PhD

In this Q&A, corresponding author Rubén Queiro, MD, PhD, associate professor at the University of Oviedo and consultant rheumatologist at the Hospital Universitario Central de Asturias in Oviedo, Spain discussed the research and its findings.

This retrospective longitudinal observational single-center study included 72 patients (mean age 50 years; 72% women) with PsA who had received at least 1 dose of ixekizumab. More than 90% received 2 or more biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs prior to ixekizumab. Ixekizumab showed 1- and 2-year retention rates of 65% and 57%, respectively. Meanwhile, 0.18 adverse events per person-year were identified. While the number of previous biologics did not influence drug survival, prior use of methotrexate (hazard ratio [HR] 2.31 [95% confidence interval (CI) 1.05 – 5.10], P < .05) and depression (HR 2.40 [95% CI 1.07 – 5.41], P < .05) increased the risk of ixekizumab discontinuation. Ixekizumab showed a good retention rate in patients with PsA regardless of age, gender, metabolic comorbidities, or smoking status.

HCPLive Rheumatology: Why was the study conducted?

Rubén Queiro, MD, PhD: We have carried out this study because, despite the fact that ixekizumab has been on the therapeutic market for PsA for several years now, most of the information we have about this drug comes from pivotal randomized clinical trials (RCTs) and their open-label extension phases. The information from registries or observational studies from the point of view of daily clinical practice is very scarce.

We all know that the type of patient that enters RCTs is very different from the type of day-to-day patients in rheumatology clinics. For this reason, studies that come from real-life experience provide valuable information whose dissemination should be facilitated and shared with the international rheumatology community.

HCPL: What were the surprises from the findings?

RQ: We have found very favorable data on the persistence and safety of ixekizumab in real clinical practice conditions. It must be considered that in our study we included patients with active disease, who had failed 2 or more biological and targeted-specific therapies.

In this difficult-to-approach patient population, ixekizumab retention rates at the first and second year have been optimal, and the safety profile acceptable, with no alarm signals other than what is already known with the drug. In particular, we have seen that the factors that usually penalize the persistence of other biologics (particularly female gender, previous use of other biologics, and cardiometabolic comorbidities such as obesity and others) did not affect the persistence rates of ixekizumab. On the contrary, the previous use of methotrexate and depression were associated with a worse survival of the drug.

HCPL: How significant are the findings?

RQ: Our findings show that even in populations of PsA patients with a very difficult prior therapeutic approach, ixekizumab demonstrates a good profile of effectiveness and safety, which translates into the good survival curves that we have detected in our research. This means that ixekizumab is a very good rescue option for those patients with active disease refractory to multiple lines of prior treatment.

We also show that depression stands as a universal factor of worse persistence with any biologic therapy.

HCPL: What is the current practice and how could the findings possibly change things?

RQ: Currently, at least in many European countries, it is common to start biologic therapy in PsA patients with an anti-tumor necrosis factor (TNF) biosimilar. However, we know that many patients undergoing these treatments will present persistence and safety problems. In addition, the persistence of anti-TNF drugs is greatly hampered by the comorbidities of the disease, such as obesity, for example.

Our findings show that ixekizumab works well regardless of these limiting factors for anti-TNFs. On the other hand, many anti-TNF drugs are co-prescribed with methotrexate, both to increase their persistence and their efficacy. Once again, our findings show that this co-prescribing is not necessary with ixekizumab, which may translate into less iatrogenicity and lower treatment costs per patient.

HCPL: What are the takeaway points for clinicians?

RQ: We want to highlight the high effectiveness and safety of ixekizumab in real clinical practice scenarios. Also, the non-need to co-medicate ixekizumab with methotrexate, and the high persistence of the drug in conditions where many other agents tend to have persistence problems (ie, obesity, previous failure of other biologics, female gender).

HCPL: Final thoughts?

RQ: Depression, one of the common comorbidities in psoriatic disease, penalizes the survival of any biological drug, including ixekizumab, and therefore this aspect of the disease must be detected and treated jointly with other health professionals to establish the appropriate measures. Cardiometabolic comorbidity should be considered in treatment decisions for these patients, since we are verifying how IL-17A inhibitors tend to persist better in this subgroup of patients with PsA.

Reference:

1. ^{Braña I, Pardo E, Burger S, González Del Pozo P, Alperi M, Queiro R. Treatment Retention and Safety of Ixekizumab in Psoriatic Arthritis: A Real Life Single-Center Experience. J Clin Med. 2023;12(2):467. Published 2023 Jan 6. doi:10.3390/jcm12020467}