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New Studies Solidify the Efficacy of Ixekizumab in the Treatment of Psoriatic Arthritis

April 21, 2020
A head-to-head comparison of ixekizumab and adalimumab includes a look at growing biologic alternatives, including TNF inhibitors, for this inflammatory and painful condition.

Psoriatic arthritis (PsA) is a form of inflammatory arthritis that affects up to 30% of individuals with psoriasis, or 0.25% of the total population.1 Early recognition and intervention is crucial, as the disease is frequently progressive with significant disability, and the process of joint damage begins at, or even before, the clinical onset of disease.1 Treatment of PsA is complex, given the heterogeneity of disease expression that can affect multiple organs.2

Improvements in both joint and skin disease are needed to achieve optimal improvement in health-related quality of life in patients with PsA, but many patients do not achieve a satisfactory clinical response with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Targeted biologics have changed the outcome for patients in a variety of diseases including psoriasis and PsA.

Among patients who fail to achieve adequate response to csDMARDs, biological DMARDS (bDMARDs) offer an alternative, either alone or in combination with csDMARDs. The targets of bMARDs include inflammatory cytokines such as tumor necrosis factor α (TNF), interleukin (IL)-12/23 or IL-17A. While  bDMARDs offer additional treatment options, studies of their comparative efficacy and safety in general have been limited to indirect comparisons using meta-analyses.

Results using ACR criteria showed that all treatments except abatacept were statistically superior to placebo for psoriatic arthritis. (Image: iStock)

New Study Compares bDMARDs Acting on Different Targets

A recently published Phase 3b/4 study, SPIRIT-H2H, is the first completed head-to-head trial comparing two bDMARDs in patients with active PsA who experienced an inadequate response to csDMARDs.3  Evidence suggests that combining a bDMARD with a csDMARD such as methotrexate may increase treatment response by inhibiting the development of anti-drug antibodies to bDMARDs, improving treatment persistence, and increasing the serum concentration of the bDMARD.3

In this open-label, head-to-head, blinded-assessor trial, SPIRIT-H2H, Mease and colleagues sought to determine whether ixekizumab (IXE) is superior to adalimumab. IXE is a high-affinity monoclonal antibody that selectively targets IL-17A and which is the most recent addition to the PsA treatment armamentarium. Adalimuab is a TNF inhibitor that has been FDA-approved for psoriatic arthritis since 2008.3 Participants in the study had active PsA and an inadequate response to csDMARDs. To meet endpoints, they had to demonstrate improvements in both arthritis and skin symptoms. Patients had to have had PsA for at least 6 months; they were permitted to continue their csDMARD therapy.

After 24 weeks, IXE showed superiority to adalimumab in achieving a ≥ 50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100) (36% vs 28%; P = 0.036).3 Results also showed that IXE was non-inferior to adalimumab for achieving the ACR50 response (51% vs 47%) and superior to adalimumab for achieving the PASI100 response (60% vs 47%; P = 0.001). IXE also showed greater responses than adalimumab in additional PsA, skin, nail, treat-to-target, and quality-of-life outcomes. Serious adverse events were reported in 8.5% of adalimumab and 3.5% of IXE patients.

According to the investigators, a key strength of this study is its relevance to real-world clinical settings in that all patients received active treatments and were aware of which treatments they received. This may have contributed to increased responses, as all patients knew they were receiving an active therapy but to minimize bias, key outcomes were measured by blinded assessors.

Results Corroborated in Meta-Analysis

While there is extensive clinical experience with TNF inhibitors, there is little information on how these therapies compare to those with a different mechanism of action. Network meta-analyses (NMAs) are often used to inform evidence-based decision-making by combining direct and indirect evidence to expand the scope of traditional pairwise indirect comparisons.4

A newly published NMA to evaluate the relative efficacy of bDMARDs in PsA includes the recently approved IXE, expanding the available evidence on these agents and adding support to the SPIRIT-H2H findings.5 According to the study authors, it is one of the most comprehensive NMAs to date, as it includes a wide range of comparators and measures commonly investigated efficacy and safety outcomes. These include the ACR criteria, Psoriasis Area and Severity Index (PASI), and the PASI.

Results using ACR criteria showed that all treatments except abatacept were statistically superior to placebo. Infliximab was most effective, followed by golimumab and etanercept, which were statistically superior to most other treatments. Ixekizumab, in either the 2-week or 4-week dosing regimen, was statistically superior to abatacept, apremilast, and ustekinumab.

The PsARC responses showed that ixekizumab did not differ significantly from other therapies, except for golimumab, infliximab, and etanercept, which were superior to most other agents including ixekizumab.

The PASI responses, which assess skin symptoms, showed that infliximab was most effective, but not statistically superior to ixekizumab, which was the next best performing agent. There were few differences between treatments in the analysis of safety endpoints.

This NMA adds weight to the body of knowledge that can inform evidence-based decision-making in clinical practice and is particularly timely because it corroborates the recent SPIRIT-H2H findings. The bottom line, however, is that the analysis confirmed the efficacy and safety profile of all bDMARDs used in patients with active psoriatic arthritis.

Last updated on: April 21, 2020
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