Xeljanz eases spinal inflammation in ankylosing spondylitis: Phase 2 trial
Reductions seen in posterolateral spine, facet joints — important treatment targets
Reductions were seen in the posterolateral spine and facet joints, which are commonly affected in AS and represent important treatment targets, but are often excluded from MRI analyses, noted the researchers in “Tofacitinib Reduces Spinal Inflammation in Vertebral Bodies and Posterolateral Elements in Ankylosing Spondylitis: Results from a Phase 2 Trial,” which was published in Rheumatology and Therapy.
Marketed by Pfizer, Xeljanz is an oral therapy approved for adults with active AS who don’t respond to or tolerate one or more TNF blockers. It’s also cleared for other inflammatory conditions, including moderate to severe rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis.
It works to inhibit Janus kinases, enzymes that regulate the production of inflammatory molecules linked to autoimmune and inflammatory conditions such as AS.
The Phase 2 trial (NCT01786668), conducted before the therapy’s approval for AS, evaluated whether Xeljanz was effective and safe for adults with AS who had active disease despite anti-inflammatory treatment.
It enrolled 207 people who were randomly assigned to receive oral Xeljanz (2, 5, or 10 mg) or a placebo twice daily for 12 weeks, or about three months, followed by a four-week follow-up period.
Its main goal was to evaluate the percentage of patients considered responders on the Assessment of SpondyloArthritis International Society 20% (ASAS20) after 12 weeks, defined as a 20% reduction across four domains — patient global assessment of disease, pain, function, and inflammation.
Analyzing MRI data of Xeljanz treatment
Results showed 80.8% of patients on 5 mg of Xeljanz achieved an ASAS20 response, a significantly higher response rate than the placebo group’s 41.2%.
A later trial analysis indicated Xeljanz led to clinically meaningful reductions in inflammation of the spinal and sacroiliac joints for about a third of patients. The sacroiliac joints connect the spine to the pelvis and are commonly the first affected in AS.
More post-hoc analyses of MRI data from the trial participants was conducted. A post-hoc analysis is one that’s designed and carried out after the study is complete. In them, the researchers utilized the Canada-Denmark (CANDEN) MRI scoring system to assess spinal inflammation and structural changes in clinically relevant areas of the spine that are commonly omitted from other MRI analysis techniques such as structures in the posterior spine, or the back part of the spine, where patients often have early lesions and inflammation that affect mobility and function.
The analysis involved 137 participants who received a placebo (44 people) or Xeljanz at 5 mg or 10 mg (93 people).
Those given Xeljanz saw significantly greater reductions in total spine inflammation scores after 12 weeks than those on a placebo, a difference that was maintained in various regions, including the vertebral body, posterior elements, corner, non-corner, facet joint, and posterolateral areas.
The findings in the posterolateral areas and facet joints were new, the researchers noted. These areas are types of synovial joints, fluid-filled spaces between bones that enable movement.
“Synovial joints … are associated with inflammatory lesions in early AS, and are therefore important treatment targets,” the researchers wrote.
CANDEN scoring can also look at other structural changes in the spine, including the presence of fat lesions or bone erosion.
New fatty corner lesions, a type of fat infiltrate that forms in the corners of the vertebral bodies that make up the spine, were more likely in areas with persistent inflammation or where inflammation was resolved after 12 weeks of Xeljanz treatment than in places where there’d never been inflammation.
That’s consistent with the idea that these fat lesions are an intermediate step in tissue repair after inflammation, the scientists noted.
Greater reductions in bone erosion were observed with Xeljanz, but the findings were not statistically significant. Changes in inflammation scores and sub-scores were weakly correlated with most clinical outcomes in patients.
“This relative disconnect may be caused by a variety of factors, such as inflammation outside the spine,” the researchers said, noting further research should study “the relationship among CANDEN MRI outcomes, clinical response and disease activity” and real-world settings.
Further analyses supported the reliability of the CANDEN scoring system, which scientists believe should be used further to monitor inflammatory and structural changes in the spine in response to therapy.
“These results add to the understanding of the efficacy of [Xeljanz] in patients with AS, while further validating CANDEN as an approach for assessing inflammatory lesions associated with AS,” they said.