Background/Purpose: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A. It has been approved to treat adult patients with moderate-to-severe plaque psoriasis and adult patients with active psoriatic arthritis (PsA). Exposure-response relationships nowadays provide important information to help determine the optimal dose/regimens.¹ The analyses described herein characterized the exposure-efficacy relationships for 20, 50, and 70% improvement in the American College of Rheumatology criteria (ACR 20, 50, and 70, respectively) at Week 24, using data from 2 Ph3 PsA studies.

Methods: In both Ph3 studies, Ixekizumab was administered subcutaneously as a 160mg starting dose followed by repeated 80mg doses given every 2 weeks (Q2W) or every 4 weeks (Q4W). An ordered categorical model was used to describe the relationship between observed ixekizumab serum concentrations and the likelihood of ACR response at Week 24. Data from placebo patients were also included in the model fitting to allow estimation of the placebo effect. Using this model, ACR20/50/70 responses were fit simultaneously, and patient specific factors affecting the ACR response rates were explored.

Results: The models adequately characterized the ACR20/50/70 responses at Week 24. The ACR model results suggested similar efficacy between the 80mg Q2W and Q4W dosing regimens, consistent with the trial observations, and a relatively flat exposure – ACR response relationship in the ixekizumab serum concentration range observed in the trials. Age and sex were found to be significant covariates for the drug effect on ACR responses, which however do not affect the selection of optimal regimen for PsA treatment.

Conclusion: In patients with active PsA, the exposure response analyses suggest that increasing the dosing frequency from Q4W to Q2W would not offer additional clinically important ACR improvement. The analyses support the approved ixekizumab regimen for PsA patients, i.e., 160mg at week 0, followed by 80mg given Q4W as the recommended dose.

REFERENCES:

[1] FDA. Guidance for industry: exposure-response relationships – study design, data analysis, and regulatory applications. (2003)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/exposure-response-analyses-to-describe-the-relationship-between-ixekizumab-concentrations-and-acr-responses-in-psoriatic-arthritis-patients/