Inflammation May Lead to Underestimating Efficacy of TNF Inhibitors, Study Suggests

The efficacy of TNF inhibitors in slowing disease progression in people with ankylosing spondylitis (AS) may be underestimated due to inflammation when treatment is started, new research suggests.

The findings were presented in a session, titled “Tumor Necrosis Factor Inhibitors Slow Radiologic Progression in Patients with Ankylosing Spondylitis: 18-year Longitudinal Cohort Study,” at the recent 2019 American College of Rheumatology/Association for Rheumatology Professionals Annual Meeting.

Tumor necrosis factor (TNF) is a molecule that drives inflammation, and helps the immune system fight diseases and infections. In AS, excessive levels of TNF contribute to pain and swelling in the joints of the spine. Inhibitors — such as Enbrel (etanercept), Humira (adalimumab), and infliximab (brand names Remsima, Remicade) — block TNF and are common treatments in AS and other inflammatory disorders.

Yet, frequent changes in AS disease activity and in medication have made it difficult to assess the efficacy of these medications in slowing radiographic progression, meaning progression assessed via imaging. Also, high levels of inflammation when treatment was initiated may have precluded a correct analysis of the effects of TNF inhibitors.

Investigators from the Republic of Korea addressed this by using data from 328 people (mean age of nearly 33 years), who were treated with TNF inhibitors at a single site over 18 years. The data were assessed in 2,315 intervals, defined as periods of time spent on or off of these therapies.

Radiologic progression was assessed by calculating the rate of change in the Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).

Results showed that this rate was significantly lower in “on” compared to “off” intervals — 0.916 vs. 0.970 per year.

However, the researchers said that the impact of the TNF inhibitors was underestimated, because erythrocyte sedimentation rates and levels of c-reactive protein — two markers of inflammation — were significantly higher at the start of “on” treatment intervals.

When the team accounted for the effects of these markers, the rate of mSASSS change per year showed a greater difference favoring the use of TNF inhibitors — 0.848 on vs. 0.959 off treatment.

“TNF inhibitor treatment significantly slowed radiologic progression,” the scientists wrote. “In addition, the effect of TNF inhibitors on radiological progress has been previously underestimated.”