Combo Therapy Slows Progression in Ankylosing Spondylitis

Nancy A. Melville

September 18, 2016

GHENT, Belgium — The progression of ankylosing spondylitis can be slowed when tumor necrosis factor (TNF) inhibitors are added to high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), possibly because of a synergistic effect between the two drugs, according to new research.

"This is the first study to show a relation between these drugs, and the first long-term longitudinal cohort study looking at drug effects on progression," said investigator Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco Medical Center.

She presented the research here at the International Congress on Spondyloarthritides 2016.

All 527 patients had ankylosing spondylitis with at least 2 years of clinical and radiographic imaging follow-up. Mean follow-up was 3.67 years.

Disease progression was defined as an increase of at least 2 units on the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over 24 months.

The propensity-score analysis was adjusted for factors such as disease duration, sex, race, education level, comorbidities, smoking, C-reactive protein levels, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, and baseline mSASSS.

Of the 42% of patients who used TNF inhibitors in the first interval of the study, 10% had a high NSAID-use index. Of the 58% of patients who did not use TNF inhibitors, 20% had a high NSAID-use index.

After multivariate adjustment, the probability of radiographic progression was lower for patients with a high NSAID-use index who used TNF inhibitors than for those who did not use TNF inhibitors; in fact, the reduction was much as 70% (odds ratio, 0.30; P = .05).

For patients with a low NSAID-use index or no NSAID use, rates of radiographic progression were not significantly different between users and nonusers of TNF inhibitors.

The combination of TNF inhibitors and NSAIDs is typically not recommended for patients with ankylosing spondylitis, Dr Gensler told Medscape Medical News. However, in some cases, symptoms dictate the combination, and in other cases, overlap can occur during the course of treatment.

"Patients are expected to try a course of NSAIDs before stepping up to a TNF inhibitor, and they are often on both in the initial stage of starting the TNF inhibitor," she explained. "Most will stop or taper the NSAID when symptoms are controlled."

The mechanism of the synergistic effect between the two drugs could be related to a combined anti-inflammatory effect, Dr Gensler speculated.

"NSAIDs have been used to prevent heterotrophic ossification in surgical patients for years, and TNF inhibitors obviously suppress inflammation and promote the repair of erosions," she explained. "It is possible that together they optimize control of inflammation and prevent new bone both directly and indirectly."

The effects of these drugs on disease modification and the progression of ankylosing spondylitis are a matter of debate. Clinical trials of TNF inhibitors have shown no effect on progression; however, Dr Gensler was involved in a previous study that showed evidence of a protective effect of TNF inhibitors (Arthritis Rheum. 2013;65:2645–2654).

Although the current study is the first to show a combined effect of NSAIDs and TNF inhibitors on disease progression, Dr Gensler said that longer-term studies are needed.

"This study implies a causal relation; however, unmeasured confounders are possible," she said. Still, it does start "to give a more granular look at the potential benefit, aided by the power in the numbers — both of patients and in follow-up time."

"Additional analyses need to be done, and validation in another cohort — or better, in a randomized controlled trial — to examine the relation would be optimal," she added.

 
For the moment, I would say this looks more like residual confounding than a true effect.
 

"It's hard to say whether this reflects a real effect," said Robert Landewé, MD, professor of rheumatology at the Amsterdam Rheumatology & Immunology Center, who is copresident of the meeting.

"For the moment, I would say this looks more like residual confounding than a true effect," he told Medscape Medical News. Nevertheless, the study contributes an intriguing theory for discussion, Dr Landewé said.

"There has been ongoing discussion about whether TNF inhibitors inhibit radiographic progression, and this brings another nuance of the story," he explained. "I have not seen this in previous studies. It's a new angle in the discussion and it's very interesting."

The study was funded by the National Institutes of Health. Dr Gensler is a consultant for AbbVie, Amgen, Janssen, and Novartis. Dr Landewé has consulted for Janssen.

International Congress on Spondyloarthritides (SPA) 2016: Abstract 09. Presented September 17, 2016.

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