Under-the-skin treatment with ixekizumab leads to early and sustained reductions in pain, fatigue, and inflammation, as well as significant improvements in sleep and quality of life, as reported by patients with ankylosing spondylitis (AS) who took part in two Phase 3 trials.
The research, “Translating Improvements with Ixekizumab in Clinical Trial Outcomes into Clinical Practice: ASAS40, Pain, Fatigue, and Sleep in Ankylosing Spondylitis,” appeared in the journal Rheumatology and Therapy.
Ixekizumab is an engineered antibody that selectively inhibits interleukin (IL)-17A, an immune protein with an important role in AS disease processes. It belongs to a type of therapy known as biological disease-modifying anti-rheumatic drugs (bDMARD) and is currently marketed as Taltz (by Eli Lilly) for the treatment of active psoriatic arthritis and plaque psoriasis, two chronic inflammatory diseases.
Early results of two Phase 3 clinical studies, named COAST-V (NCT02696785) and COAST-W (NCT02696798), showed ixekizumab’s efficacy over 16 weeks, both in patients who had never received treatment with a bDMARD and those who had not responded to or had been intolerant to tumor necrosis factor inhibitors (TNFi).
The two trials used ASAS40 — Assessment in Ankylosing Spondylitis — which means that patients needed to show improvement/reduction of at least 40% in at least three out of four domains: patient global assessment of disease, pain, function, and inflammation.
COAST-V and -W showed significantly higher proportions of ixekizumab-treated patients achieving ASAS40 compared to placebo. Yet, as changes in clinical symptoms are the main focus of treatment in daily practice, the real-world impact of an ASAS40 response remains to be determined.
The team at Eli Lilly and institutions in North America, Europe, and Taiwan addressed this gap by analyzing the improvement in ASAS40 and other outcomes, as well as by quantifying changes in patient-reported measures in people achieving ASAS40 in COAST-V and -W compared to those who did not achieve ASAS20 (a 20% difference in the four domains).
Participants in the two studies had AS symptoms for a mean 16.0 and 18.4 years, respectively, and had been diagnosed 7.7 and 11.6 years prior to COAST-V and -W, respectively. Both trials included patients with very high disease activity — 341 in COAST-V and 316 in COAST-W.
In the two studies, the starting dose of ixekizumab was 80 mg or 160 mg, with different subgroups receiving 80 mg of the therapy every two or four weeks thereafter.
The results confirmed that, compared with placebo, treatment with ixekizumab led to significantly greater improvement in the four ASAS domains in both trials as early as week 1. Of note, the group treated with 40 mg of adalimumab (brand name Humira) in COAST-V also showed significant benefits in ASAS over placebo.
Benefits upon receiving ixekizumab were also seen in spinal pain at night, sleep quality, and fatigue. In both trials, ixekizumab also led to reduced overall disease activity (via BASDAI scores) and better health-related quality of life.
Compared to the ASAS20 non-responders, ixekizumab-treated patients who achieved ASAS40 had significantly greater mean changes in spinal pain at night, fatigue, sleep quality, and the Short Form 36-Item Physical Component Summary of quality of life regardless of prior treatment with a bDMARD.
Specifically, compared to patients not achieving ASAS20, ASAS40 responders showed a 2.6 to 5.3-times greater improvement/reduction in pain, fatigue, sleep, and quality of life if not previously treated with a bDMARD, and a 5.1 to 18.5 times greater improvement if previously receiving at least one TNFi.
“The data presented here show that ixekizumab treatment leads to greater improvements in patient-reported AS symptoms versus placebo treatment, including pain, fatigue, function, inflammation, sleep, and overall [quality of life],” the scientists said.