Ixekizumab improves signs and symptoms in TNFi-naïve PsA patients

Data from a post-hoc analysis show that use of ixekizumab improves signs and symptoms of difficult-to-treat psoriatic arthritis (PsA) patients who previously failed to respond to 1 or 2 TNF inhibitor (TNFi) therapies.

“PsA is a progressive, chronic inflammatory disease that is often treated with TNFi when conventional treatments have failed. We have learned from rheumatoid arthritis (RA) and PsA that patients with an inadequate response to the first TNFi generally have a decreased response to subsequent TNFi,” said Dr Amanda Gellett (Eli Lilly, USA). In addition, in a substantial proportion of patients, TNFi therapy might be contra-indicated or not tolerated. “Also, nearly 40% of the patients in this population switched TNFis as part of their routine care, and that was mainly due to lack of efficacy,” added Dr Gellett. Therefore, therapies with an alternative mechanism of action in PsA are clinically important.

The anti–interleukin-17 drug ixekizumab selectively binds to IL-17A. “There is proof for the treatment of active PsA in moderate-to-severe plaque psoriasis. In PsA, ixekizumab has shown efficacy in biologic-naïve patients in the SPIRIT-P2 study and in patients with an inadequate response or intolerance to one or two TNF-inhibitors,” continued Dr Gellett [1,2]. The objective of this post-hoc analysis was to assess the efficacy of ixekizumab in patients who had an inadequate response to one or two TNFis.

In the double-blind, multicentre, randomised, placebo-controlled, phase 3 study SPIRIT-P2, patients were recruited from 109 centres across ten countries. Eligible patients were ≥18 years old, had a confirmed diagnosis of PsA for at least 6 months, and had a previous insufficient response to TNFi therapy. Patients were randomised to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks (n=122) or every 2 weeks (n=123) after a 160 mg starting dose, or placebo for up to 24 weeks.

Efficacy was measured by proportion of patients reaching ACR50, an improvement in HAQ-DI ≥0.35, minimal disease activity (MDA), DAS28-CRP EULAR Good Response criteria, and DAPSA ≤14. “It was concluded that both doses improved PsA signs and symptoms regardless of prior inadequate response to one or two TNF-inhibitors (see Table). In this difficult-to-treat population of patients, we saw significant improvements in week 24 in the outcomes that we studied, and the improvement was consistent.,” said Dr Gellett.

Table: Efficacy measures at week 24 of ixekizumab in patients with inadequate response to TNFi



 

1. Nash P, et al. Lancet. 2017 Jun 10;389(10086):2317-2327.
2. Gellett A, et al. Abstract OP0110. EULAR 2019

Posted on 4 September 201916 February 2024