BMI and Treatment Response to TNF Inhibitors in Ankylosing Spondylitis

Among patients with ankylosing spondylitis (AS) treated with tumor necrosis factor (TNF) inhibitors, higher body fat content before treatment predicts lower rates of response to anti-TNF therapy, according to an article published in the Journal of Rheumatology.

Data demonstrate that among patients with AS, body mass index (BMI) in the overweight or obese range is linked to a lower likelihood of clinical improvement with TNF inhibitor therapy. One possible explanation for this link is that adipose tissue produces cytokines that may have a pro-inflammatory effect on immune processes.

However, BMI does not capture whole body fat composition or the distribution of fat and muscle. Limited evidence suggests TNF inhibitor treatment in AS is associated with increases in fat mass, abdominal obesity, and visceral and subcutaneous adipose tissue.

Sebastián Ibáñez Vodnizza, MD, from Clínica Alemana de Santiago and Padre Hurtado Padre in Chile, and Irene van der Horst–Bruinsma, MD, PhD, from VU University Medical Center in the Netherlands, evaluated whether body fat composition was related to clinical outcomes after TNF inhibitor treatment in patients with AS.

Of 41 participants with AS, 61% were men. All patients were TNF inhibitor-naive and were treated with adalimumab or etanercept, with a median follow-up of 14.3 months. Dual-energy x-ray absorptiometry was used to measure body fat composition.

After adjusting for age and sex, pretreatment higher body fat percentage (odds ratio [OR], 0.8), fat mass index (OR, 0.7), and fat mass index percentile (OR, 0.9) were associated with lower rates of clinically important improvement with anti-TNF treatment, as measured by Ankylosing Spondylitis Disease Activity Score containing C-reactive protein.

Higher fat mass index percentile at baseline (OR, 0.95) was also correlated with a lower likelihood of attaining clinically important improvement by the Bath Ankylosing Spondylitis Disease Activity Index.

After adjusting for sex and age, percentiles for fat mass index and body fat percentages were similar for women and men. Muscle wasting may have been more common in women, who had higher fat free mass index percentages. Body composition did not change significantly between baseline and follow-up after treatment, but a trend toward muscle recovery, as measured by fat free mass index, was identified in men.

Summary and Applicability

Higher BMI at baseline is associated with a lower likelihood of treatment response in patients with AS receiving TNF inhibitor therapy. However, BMI does not differentiate between fat and muscle mass, and thus does not provide information about body fat composition or distribution. Researchers sought to determine whether body fat composition affects clinical response to TNF inhibitor treatment among patients with AS.

“We found that a higher fat mass content, corrected for height and independent of gender and age, is related to a worse response to TNF alpha blockers,” Dr van der Horst–Bruinsma told Rheumatology Advisor.

“The reason for this association is unclear,” Dr van der Horst–Bruinsma added. “It seems unlikely that the worse response is due to a larger area of distribution since, after the multivariate analysis, the total fat mass was not related to a worse response. We are going to investigate fat metabolism in the near future to unravel this mechanism.”

Limitations and Disclosures

As the result of a small sample size, this study may have been underpowered to detect differences in outcomes related to differences in fat mass indices between men and women.

Dr van der Horst–Bruinsma reports no relevant disclosures.

Reference

Ibáñez Vodnizza SE, Nurmohamed MT, Visman IM, et al. Fat mass lowers the response to tumor necrosis factor-α blockers in patients with ankylosing spondylitis [published online July 15, 2017]. J Rheumatol. doi: 10.3899/jrheum.170094