Rare diseases

Combining NSAIDs and TNFi may slow radiographic progression in AS

A/Prof Lianne Gensler

Patients with ankylosing spondylitis (AS) show less radiographic progression after four years if they take NSAIDs as well as TNF inhibitors, a prospective US study has found.

Presenting their findings at the Annual European Congress of Rheumatology (EULAR 2018) in Amsterdam, researchers said that until now the data on the impact of combined therapy on radiographic progression was limited because many AS patients discontinue NSAIDs when they are put onto TNF inhibitors.

Associate Professor Lianne Gensler, a rheumatologist at the University of California, San Francisco, said the evidence for the impact of TNF inhibitors on radiographic progression was unclear despite their good clinical efficacy, and clinical trials using continuous versus on-demand NSAIDs have had mixed results.

“This brings up the question of whether there are differential effects across NSAIDs, not every NSAID may be the same,” she told the meeting.

In a prospective cohort study Dr Gensler and colleagues sought to explore the effects of TNF inhibitors on radiographic progression in ankylosing spondylitis and to determine if NSAID dose and type altered this relationship.

The study included 519 patients with ankylosing spondylitis who met the Modified New York criteria with at least four years of clinical and radiographic follow up. The average age of participants was 41.4 years with an average symptom duration of 16.8 years. Three quarters of the patients were male, and NSAIDs were used by 66% of patients, of whom half had a high intake. Celecoxib was used by 17% of NSAID users and DMARDs by 15%. TNF inhibitors were used in 46% of patients.

Over the trial period the odds of radiographic progression for TNF inhibitor users was 41% lower [non-significant] for the 3.6–5.9 year duration of use than in non-users. In patients taking TNF inhibitors there was a significant dose-related interaction (p=0.01) between NSAID use and TNFi in relation to radiographic progression. Patients exposed to both TNFi and with high NSAID use had an Odds Ratio for progression of 0.31, compared to those not on high dose NSAIDs (OR=1.23).

When NSAID-specific effects were examined, celecoxib was associated with the greatest reduction in radiographic progression and this was significant at both two and four years.

The mean difference in mSASSS between TNF inhibitor and no TNF inhibitor use for celecoxib was -3.98 (p<0.001) and -4.69 (p<0.001) at two and four years respectively.

“Our results suggest that the use of TNF inhibitors and NSAIDs, particularly celecoxib, have a synergistic effect to slow radiographic progression in AS patients, particularly at higher doses,” Dr Gensler told the EULAR meeting.

She acknowledged that the results might have been subject to unmeasured confounders, but said this would have to be quite a large effect to overcome or negate the findings.

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