Markers of Radiographic Spinal Progression in Ankylosing Spondylitis

Serum leptin and high molecular weight adiponectin (HMW-APN) have an inverse relationship with radiographic spinal progression in patients with ankylosing spondylitis (AS), according to findings published in Arthritis Research & Therapy.¹ In a post-hoc analysis of the Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on Radiographic Damage in AS (ENRADAS) trial, researchers also found that women tend to have higher levels of leptin and APN and therefore less severe structural damage than men.

AS, which affects more men than women, has no cure.² Patients’ symptoms, however, can be treated with NSAIDs, tumor necrosis factor inhibitors (TNFi), physical therapy, and surgery.^2,3

The original ENRADAS study, a 2-year trial that investigated the efficacy and safety of continuous vs on-demand diclofenac in 167 patients with AS (ClinicalTrials.gov identifier: NCT00715091), found that on-demand NSAIDs — but not continuous NSAID administration — reduced the radiographic spinal progression as measured by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, 0.79 vs 1.28, respectively; P =.39).⁴

The ENRADAS sub-analysis was based on a 2-year follow-up of 120 patients (mean age, 42.9±10.3; 68.3% men). Researchers defined radiographic spinal progression as a worsening of the mSASSS by ≥2 points or the formation or progression of new syndesmophytes after 2 years.

Based on a literature search of the association between adipokines, inflammation, and bone metabolism, serum leptin and adiponectin levels were measured at baseline and after 2 years with enzyme-linked immunosorbent assays.

Of the 8 adipokines tested, leptin and HMW-APN had the strongest association with reduced radiographic spinal progression. For leptin and HMW-APN levels, the odds ratios (OR) for no mSASSS progression were 1.16 (95% CI, 1.03-1.29) and 1.17 (95% CI, 0.99-1.38), respectively. The OR between syndesmophyte formation or progression and leptin and HMW-APN levels were 1.29 (95% CI, 1.11-1.50) and 1.18 (95% CI, 0.98-1.42), respectively.

Women had significantly higher levels of leptin (24.4 ng/mL vs 10.6 ng/mL, respectively; P <.001) and HMW-APN (8.04 µg/mL vs 5.07 µg/mL, respectively; P <.001) than men, indicating that these adipokines may serve as potential sex-linked biomarkers or pathophysiologic factors that predict radiographic spinal progression.

“This is a post-hoc analysis of the ENRADAS trial. We could find that higher serum levels of adipokines leptin and adiponectin (high molecular weight fraction) play a protective role regarding progression of structural damage in the spine (new bone formation) in patients with ankylosing spondylitis,” noted Denis Poddubnyy, MD, in an interview with Rheumatology Advisor.

“Females had in general higher levels of both adipokines as compared to males. These data are especially interesting in light of the fact that female patients with ankylosing spondylitis usually develop less structural damage in the spine as compared to males,” said Dr Poddubnyy. “Thus, our data indicate that naturally higher levels of leptin and adiponectin might protect females with ankylosing spondylitis from structural damage development in the spine.”

Summary and Clinical Applicability

The higher the levels of serum leptin and HMW-APN, the less likely patients with AS would show radiographic spinal progression. Leptin and HMW-APN, which were thought to be markers of bone metabolism, might also have an impact on new bone formation. Women tend to have higher levels of leptin and APN than men with AS, which may account for their lower prevalence of new spinal bone formation.

Limitations and Disclosures

• Few women (n=38) were included in the trial
• There were no additional adipose tissue assessments beyond accounting for body mass index.
• The study did not include patients taking biologics

The German Ministry of Education and Research funded the ENRADAS study and Novartis donated diclofenac, the original study drug.

References

1. Hartl A, Sieper J, Syrbe U, et al. Serum levels of leptin and high molecular weight adiponectin are inversely associated with radiographic spinal progression in patients with ankylosing spondylitis: results from the ENRADAS trial. Arthritis Res Ther. 2017;19(1):140. doi:10.1186/s13075-017-1350-9

2. National Institute of Arthritis and Muskuloskeletal and Skin Diseases. What is Ankylosing Spondylitis? www.niams.nih.gov/health_info/ankylosing_spondylitis/ankylosing_spondylitis_ff.pdf. Accessed July 5, 2017.

3. Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2016;68(2):282-298. doi:10.1002/art.39298

4. Sieper J, Listing J, Poddubnyy D, et al. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis. 2016;75(8):1438-1443. doi:10.1136/annrheumdis-2015-207897