TNF Inhibitors Significantly Slow Bone Damage in AS, Long-term Study Finds

Disease progression slowed significantly in people with ankylosing spondylitis (AS) when they were on TNF inhibitors, compared to when they were off the medications, a long-term study has found.

This protection from bone damage remained significant even after accounting for factors that influence the progression of radiologic disease.

The study, “Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence,” was published in the journal Annals of the Rheumatic Diseases.

TNF inhibitors, such as Remicade (infliximab), Simponi (golimumab), Enbrel (etanercept), and Humira (adalimumab), are a therapeutic mainstay for people with AS who fail to respond to non-steroidal anti-inflammatory drugs (NSAIDs).

These medications reduce inflammation and may stop disease progression by blocking the effects of tumor necrosis factor (TNF), a key inflammatory mediator. But whether they also reduce the rate of bone damage remains unclear.

While clinical trials have shown no differences in radiologic disease progression with TNF inhibitor treatment for two years, more recent studies suggest that long-term or earlier treatment with these agents may impact radiographic disease progression.

To address this question, researchers in South Korea examined real-world data from AS patients followed at the Hanyang University Medical Center between January 2001 and December 2018, who received at least one TNF inhibitor over their lifetime. The progression of radiographic damage was assessed with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).

To avoid certain confounding factors, the researchers examined the radiographic progression rate of patients while on TNF inhibitors and while not receiving these therapies. Such approach enabled patients to be their own controls.

The team also used statistical methods to account for the fact that TNF inhibitors are often given to patients when their disease is more severe, and thereby more likely to progress on radiographic exams.

The study included 338 participants who were prescribed TNF inhibitors, as assessed via their prescriptions on electronic medical records, and had at least one period off such medicines.

Patients had been diagnosed at a mean age of 33.1 years, and had the disease for an average of 12.6 years at the time of the analysis. They had been treated with TNF inhibitors for a mean period of 6.6 years.

In total, the scientists examined 2,364 treatment intervals among the 338 patients. Each interval lasted over a mean of 439 days, but periods on TNF inhibitors lasted longer (633 days) than periods without such medications (210 days).

In a first analysis, changes in mSASSS were significantly associated with age at diagnosis, the presence of the genetic marker HLA-B27, eye involvement, female sex, inflammation status at the start of the interval, and use of disease-modifying anti-rheumatic drugs and TNF inhibitors.

However, after accounting for the factors that impact TNF inhibitor use — including inflammation and NSAID use — and removing variables with disproportionate numbers of intervals on and off treatment, only eye involvement and inflammation markers at the start of the treatment period remained as significant predictors of more severe worsening in mSASSS scores.

In turn, being female, having higher disease severity scores — assessed with the Bath Ankylosing Spondylitis Disease Activity Index — and TNF inhibitor use remained as significant predictors of reductions in the rate of radiographic disease progression.

Notably, in this analysis, patients worsened an average of 0.914 points per year on their mSASSS scores while using TNF inhibitors, compared with 0.970 points per year while off these medications.

This difference became greater when a statistical model accounting for greater inflammation status at the time of TNF inhibitor start was employed. In this model, patients worsened about 0.848 points per year on their mSASSS scores, versus 0.960 points per year without these treatments.

The investigators noted several limitations to their study, including the lack of data on smoking status, the exclusion of patients who never received TNF inhibitors, and the possibility that estimated mSASSS values do not correspond to actual values.

Yet, “our study provided strong evidence that TNFi therapy slows the radiographic progression by overcoming the limitations of previous studies,” they concluded. “Treatment using TNFis is among the modifiable factors for radiographic progression in patients with AS.”