EULAR 2015: Emerging Concepts, Treatments for Axial Spondyloarthritis

Determining the efficacy of treatment in Axial SpA requires patience.
Image Credit: Hriana/shutterstock.com

ROME, Italy—When it comes to thinking about disease modification—a main goal in the treatment of axial spondyloarthritis (axial SpA) and other inflammatory diseases—it’s time to reconsider the concept, an expert said at EULAR 2015, the annual congress of the European League Against Rheumatism (EULAR).

The traditional way of assessing disease modification, inhibiting radiographic progression, is essentially out of date because it is kept in check so well by today’s treatments, said Robert Landewé, MD, professor of rheumatology at the University of Amsterdam.

“We don’t see a lot of radiographic progression anymore,” Dr. Landewé said. For that reason, these changes might have fallen out of line with true outcomes and what really is important to patients.

Maintain Structural Integrity

He proposed a paradigm shift—to start thinking of disease modification as maintaining structural integrity.¹

“That is what, in patients with rheumatoid arthritis, really matters,” he said. It’s what matters to patients with axial SpA, too, he proposed, except that the concern with structural damage in axial SpA is prevention of bone formation rather than bone erosion.

The use of structural progression to assess disease modification was borne out in a 2014 study of ankylosing spondylitis patients that found that those with the highest disease activity (ASDAS) scores were also the ones that saw the greatest rise in structural progression on modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).²

Dr. Landewé cautioned, though, that there are some potential problems if this approach is used. Negative results have been seen multiple times in studies using anti-TNF treatment done over two-year periods—although there is some question about whether there is really no inhibition of structural progression or whether the results reflect a methodological problem with the studies, Dr. Landewé said.

Also, syndesmophyte formation early in axial SpA is fairly rare, making it difficult to address in the context of clinical trials. There is also the question of whether assessing syndesmophyte formation is actually enough, Dr. Landewé said. “Or is it only a component, and we want to know far more?” he wondered.

Dr. Landewé suggested that a “modern concept” of disease modification in axial SpA should involve an integrated approach of long-term suppression of disease activity; preserving structure; preventing disease-related co-morbidities; and preserving physical function and general health.

Treatment Results

The understanding of the nuances of treatment of axial SpA is broadening, said Joachim Sieper, MD, PhD, head of rheumatology at Charité University Hospital in Berlin.

Recent studies have shown that, if TNF blockers are to be used, early treatment of the disease is extremely important.

Also, positive MRI findings or elevated C-reactive protein levels are a good indication of which patients with non-radiographic axial SpA will respond to TNF inhibitors. A 2013 study found that 41% of those meeting either of those criteria had an ASAS40 response to adalimumab, compared with 14% who didn’t achieve that response. Among those who were both MRI negative and had normal CRP, there was no significant difference in response.³

Researchers have found that treatments targeting IL-17 and IL-23 yield good results on disease activity and function.⁴

Dr. Sieper also pointed out that there is evidence that radiographic progression might not necessarily mean worse function. One study on patients treated with TNF blockers over 10 years found that Bath Ankylosing Spondylitis Functional Index (BASFI) scores stayed low even as mSASSS scores escalated.⁵

“In these patients with longstanding AS, there was no effect of the TNF blockers on the structural damage,” he said. “However, this did not seem to matter in these patients regarding function and spine mobility.”

Women & SpA

In another talk on axial SpA, Irene van der Horst-Bruinsma, associate professor of rheumatology at VU University Medical Center in Amsterdam, said that women are more likely to have enthesitis and to experience a delay in diagnosis with lower responses to TNF blockers, leaving room to wonder whether the right outcome measures are being used for women.⁶

Also, she said, response rates are better in patients who are younger than 40, as well as in those with disease duration of fewer than four years.

She cautioned that it’s important not to stop treatment too early in older patients who have had the disease for longer periods, because patients with worse function can see their BASFI scores improve as far out as six months after treatment begins.

“We have to be patient,” she said, “to evaluate the efficacy of treatment.”

Thomas R. Collins is a freelance medical writer based in Florida.

References

1. Landewé R, Strand V, van der Heijde D. From inhibition of radiographic progression to maintaining structural integrity: A methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials. Ann Rheum Dis. 2013 Jul;72(7):1113–1117.
2. Ramiro S, van der Heijde D, van Tubergen A, et al. Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort. Ann Rheum Dis. 2014 Aug;73(8):1455–1461.
3. Sieper J, van der Heijde D, Dougados M, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013 Jun;72(6):815–822.
4. Poddubnyy D, Hermann KG, Callhoff J, et al. Ustekinumab for the treatment of patients with active ankylosing spondylitis: Results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis. 2014 May;73(5):817–823.
5. Poddubnyy D, Fedorova A, Listing J, et al. Functional status remains stable despite continuous radiographic spinal progression over ten years in patients with ankylosing spondylitis receiving anti-TNF therapy. Abstract THU0199. Presented at EULAR, June 11, 2015, Rome.
6. van der Host-Bruinsma IE, Zack DJ, Szumski A, et al. Female patients with ankylosing spondylitis: Analysis of the impact of gender across treatment studies. Ann Rheum Dis. 2013 Jul;72(7):1221–1224.