Ankylosing spondylitis pain eased with Taltz even if inflammation isn’t

COAST-V study findings suggest Taltz works differently than adalimumab

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by Lindsey Shapiro |

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Treatment with Taltz (ixekizumab) significantly eases spinal pain at night in adults with ankylosing spondylitis (AS) regardless of whether inflammation was well controlled with the therapy, according to new analyses from the Phase 3 COAST-V clinical trial.

The study tested Taltz against either a placebo or adalimumab, which is sold as Humira or biosimilars, in 341 adults with AS. The analysis wasn’t designed to directly compare Taltz to adalimumab, but the results suggested the former may have greater effects on spinal pain. The findings also support “the hypothesis that [Taltz] reduces pain in AS by mechanisms that cannot be attributed only to the reduction in inflammation, and that [Taltz] and adalimumab may differ in their pain-relieving mechanisms, suggesting [Taltz] has a greater direct effect on pain relief,” said researchers.

The study, “Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial,” was published in Rheumatology and Therapy. It was funded by Taltz developer Eli Lilly.

Pain is a common symptom of AS, an inflammatory disease of the spine, and most patients report at least moderate pain from the onset of the disease, said the researchers, who noted the mechanisms that contribute to pain in AS are likely multifactorial. Early in the disease course, it might be a result of inflammation, but later it comes from a combination of inflammation, joint, and nerve damage, and other processes.

Administered via an injection under the skin, Taltz is an approved antibody-based therapy that suppresses IL-17A, an inflammatory signaling molecule implicated in the disease. IL-17 signaling “is an effective mediator of pain processing at several levels,” the researchers wrote.

COAST-V (NCT02696785) was among the studies that supported Taltz’s approval and showed it reduced disease activity in AS patients who’d never received a biological disease-modifying antirheumatic drug (DMARD), the class of medications to which Taltz belongs.

Taltz was also associated with reductions across several symptom domains, including spinal pain and spinal pain at night.

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Here, scientists conducted a post hoc analysis of COAST-V data to assess Taltz’s effects on pain and its relationship to objective measures of inflammation. A post hoc analysis is planned and carried out after a trial has finished.

For the first 16 weeks, or about four months, of the trial, the participants were randomly assigned to receive injections of either Taltz, adalimumab, or a placebo. Taltz was given once every two or four weeks, while adalimumab and the placebo were administered once every two weeks.

After completing 16 weeks, all the adalimumab and placebo recipients were randomly assigned to either Taltz dosing regimen for the rest of the one-year study.

The participants rated their spinal pain at night on a scale of 0 (none) to 10 (most severe) at study visits and completed the bodily pain domain of a life quality questionnaire. Inflammation was assessed via MRI scans and by blood levels of an inflammation biomarker called c-reactive protein (CRP).

Monthly Taltz was generally associated with reductions in nighttime spinal pain after 16 weeks relative to a placebo, regardless of whether inflammation was well controlled or not, as assessed by MRI scans, CRP levels, or both. However, “adalimumab appeared to reduce [nighttime spinal pain] primarily when inflammation was also reduced.”

Taltz also led to reductions in general spinal pain and bodily pain after 16 weeks, independent of inflammation, while adalimumab’s effects weren’t as consistent.

Those initially given adalimumab or a placebo saw further pain reductions after they switched to Taltz, regardless of whether inflammation was controlled or not.

Both Taltz and adalimumab had direct effects on spinal and bodily pain, analyses indicated. However, Taltz “may have had a greater reduction in pain due to a greater direct effect on pain compared to adalimumab,” wrote the researchers, who emphasized the analyses weren’t designed to statistically compare the medications.

The fact that the inflammatory molecule IL-17 can also directly modulate pain perceptions in the brain and spinal cord may help explain why Taltz eases pain even when inflammation persists.

“This study supports the hypothesis proposing that IL-17 inhibition results in pain control via both inflammatory (indirect) and noninflammatory (direct) mechanisms,” wrote the researchers, who nevertheless noted the measurements used may not have fully captured all inflammation or types of pain. Still, they believe their “research will support better understanding of the full spectrum of effect of IL-17 inhibition” and aid health care professionals in choosing treatments.