Generally, guidelines recommend beginning psoriatic arthritis (PsA) treatment with tumor necrosis factor inhibitors (TNFis). However, not all patients respond to this method. Ixekizumab (IXE) improved the signs and symptoms of PsA in patients who had exhibited inadequate response to 1 or 2 TNFis.
Ixekizumab (IXE) improved the signs and symptoms of psoriatic arthritis (PsA) in patients who had exhibited inadequate response to 1 or 2 tumor necrosis factor inhibitors (TNFis), according to the results of a study published in Rheumatology.1
Generally, guidelines recommend beginning PsA treatment with TNFis. However, not all patients respond to this method. The drug survival rates of first line TNFi range from 46% to 84% at year 1 and 52% to 75% at year 2. Further, although the 2018 American College of Rheumatology (ACR) and National Psoriasis Foundation treatment guidelines for PsA encourage the use of a second TNFi, there is little evidence to show that patients with inadequate results to one TNFi respond better to another one.
“Patients with PsA who have had an inadequate response to TNFi present specific challenges to clinicians and have not been studied extensively (particularly 2 TNFi) in dedicated clinical studies,” investigators explained.
Inadequate response is defined by < 20% improvement from baseline in tender joint count (TJC) and swollen joint count (SJC). Previous studies have shown that those who switch to another TNFi after inadequate response have worse outcomes than those who do not switch. Investigators naturally theorized that switching to a mediation with different mechanisms of action may be a better option for patients with PsA.
This post-hoc analysis included data pulled from the randomized, double-blind, placebo (PBO)-controlled phase 3 SPIRIT-P2 study (NCT02349295), which followed patients with inadequate responses to 1 or 2 TNFi medications. They were initially randomized into 1:1:1 subcutaneous administration of a placebo, 80 mg of IXE every 2 weeks (n1⁄4123; IXE Q2W), or 4 weeks (n1⁄4122; IXE Q4W) after 160 mg of a placebo (PBO; n1⁄4118) for 24 weeks. The study measured results based on the number of patients achieving ≥ 50% improvement in ACR response criteria (ACR50) and 100% improvement from the baseline in the Psoriasis Area and Severity Index (PASI 100), improvement in HAQ-Disability Index (HAQ-DI) ≥ 0.35, minimal disease activity (MDA), European League Against Rheumatism (EULAR) Good Response Criteria, and Disease Activity in PsA (DAPSA) ≥ 14.
After 24 weeks, patients in the placebo group were then reassigned to the IXE Q2W or IXE Q4W groups for the second half of the study. After 32 weeks, patients who did not achieve ≥ 20% improvement in TJC and SJC were discontinued.
The study found that at week 24, patients who received IXE were significantly more likely to achieve ACR50, HAQ-DI ≥ 0.35 improvement, MDA, EULAR good response, and DAPSA ≥ 14, regardless of inadequate response to TNFi. They were also more likely to achieve ACR50 and PASI 100 simultaneously.
This analysis was conducted using participants from the SPIRIT-P2 group. In an analysis of this subset, 61% of patients had inadequate response to one TNFi and 39% were inadequate to 2 TNFi. The patients with inadequate response to one TNFi in the IXE Q4W group (the approved dose of IXE) had better results at the end of the study than those with 2 TNFi inadequate response.
As there was no placebo group in the second half, the study was limited by the lack of comparative long-term results. Additionally, as investigators were using participants from a phase 2 study, it was difficult to draw conclusions based on specific populations, like plaque psoriasis, enthesitis, or dactylitis. Lastly, investigators were not able to clearly discern whether participants have primary or secondary TNFi failures using the study data, which hindered further insights around the results.
“This post hoc analysis suggests that IXE improved the signs and symptoms of PsA in a population of difficult-to-treat patients who have had inadequate response to 1 or 2 TNFi. IXE Q2W and Q4W demonstrated improvement at week 24, which persisted among patients continuously dosed with IXE through week 52 on all the six outcomes analyzed,” investigators concluded. “Therefore, IXE may provide clinicians with an effective treatment option for patients with PsA who have failed 1 or 2 TNFi.”
Kirkham B, Sesin C, Gellett AM, Sprabery AT, Lin CY, Turkiewicz A. Improvement from ixekizumab treatment in patients with psoriatic arthritis who have had an inadequate response to one or two TNF inhibitors [published online ahead of print, 2021 Jan 20]. Rheumatology (Oxford). 2021;keaa824. doi:10.1093/rheumatology/keaa824