Ixekizumab Superior to Adalimumab in Sustained Joint, Skin Improvement in PsA

The phase 3b/4 SPIRIT head-to-head study evaluated ixekizumab (Taltz) versus adalimumab (Humira) in psoriatic arthritis.

In a head-to-head trial, ixekizumab (Taltz, Eli Lilly) demonstrated superiority to adalimumab (Humira) in psoriatic arthritis (PsA) for sustained joint and skin improvement, according to new data from the phase3b/4 SPIRIT Head-to-Head (H2H) study.

The results were presented as a late-breaking oral presentation at the American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting in Atlanta, Georgia.

Ixekizumab is currently approved for the treatment of adults with moderate-to-severe plaque psoriasis that are candidates for systemic therapy or phototherapy, as well as active PsA and active ankylosing spondylitis. PSA, a progressive form of inflammatory arthritis, causes swelling, stiffness, and pain in and around the joints and impaired physical function. Untreated PsA can lead to permanent joint damage.

For the study, the efficacy and safety of ixekizumab versus adalimumab was assessed in patients with PsA who are biologic disease-modifying antirheumatic drug (DMARD)-naïve during a 52-week treatment period. The trial utilized on-label dosing for both ixekizumab and adalimumab and allowed inclusion of concomitant conventional DMARDs.

A total of 566 patients were randomized to receive either ixekizumab and adalimumab. Of the enrolled patients, 87% of patients treated with ixekizumab, and 84% of patients treated with adalimumab participated in the study through 52 weeks.

At week 24, ixekizumab was shown to be just as effective as adalimumab in improving symptoms, as measured by the primary endpoint of simultaneous achievement of a reduction by at least 50% in disease activity as defined by the American College of Rheumatology (ACR50). However, ixekizumab was superior to adalimumab in complete skin clearance as measured by the Psoriasis Area and Severity Index (PASI 100), according to the study.

At week 52, 39% of patients treated with ixekizumab had a sustained simultaneous joint and skin improvement (ACR50 and PASI 100), compared with 26% of patients treated with adalimumab.

Additionally, other secondary endpoints at week 52 showed:

  • Fifty percent of patients treated with ixekizumab and 50% of patients treated with adalimumab achieved ACR50.
  • Thirty-five percent of patients treated with ixekizumab and 34% of patients treated with adalimumab achieved ACR70.
  • Sixty-four percent of patients treated with ixekizumab and 41% of patients treated with adalimumab achieved PASI 100.

“We currently have limited data on comparisons of the safety and efficacy of biologic therapies used for the treatment of psoriatic arthritis,” lead author Josef Smolen, MD, professor of medicine at the Medical University of Vienne, Austria, said in a statement. “The 24-week data from the SPIRIT-H2H trial demonstrated that ixekizumab, when compared to adalimumab, provided superior efficacy on the pre-specified combined endpoint of improvement in joint and skin symptoms.

In a separate head-to-head trial, adalimumab went up against secukinumab (Cosentyx, Novartis) for the treatment of PsA. Results from this trial, known as EXCEED, showed that secukinumab fell short of demonstrating superiority. Although secukinumab yielded numerically higher results, it narrowly missed statistical significance for superiority in ACR20.

According to Smolen, ixekizumab had similar efficacy to adalimumab on the joint manifestations of the disease with better efficacy on the skin. Overall, the 52- week data showed those results were consistent over time, regardless of concomitant methotrexate use, he added.

The safety profile of ixekizumab was consistent with previously-reported results, according to the study. The most common adverse reactions included infections (42% for ixekizumab and 39.2% for adalimumab), injection site reactions (10.6% for ixekizumab and 3.5% for adalimumab), allergic/hypersensitivity reactions (3.9% for ixekizumab and 4.6% for adalimumab), cytopenias (3.2% for ixekizumab and 4.2% for adalimumab), and cerebrocardiovascular events (1.8% for ixekizumab and 2.5% for adalimumab).

Ixekizumab also previously demonstrated superiority to guselkumab (Tremfya) in achieving skin clearance in patients with moderate-to-severe plaque psoriasis, according to the phase 4 head-to-head IXORA-R study.

For a review of biologics available for PsA and psoriasis, read this session recap from the National Association of Specialty Pharmacy Annual Meeting and Expo.

REFERENCE

ACR 2019: Lilly Presents 52-Week Head-to-Head (SPIRIT H2H) Data from Taltz (ixekizumab) Versus Humira (adalimumab) Trial in Psoriatic Arthritis [news release]. Eli Lilly’s website. https://investor.lilly.com/news-releases/news-release-details/acr-2019-lilly-presents-52-week-head-head-spirit-h2h-data-taltzr. Accessed November 12, 2019.