Etanercept is associated with a 2- to 4-fold increased risk for anterior uveitis (AU) in patients with ankylosing spondylitis (AS), compared with infliximab or adalimumab, according to a study published in the Annals of the Rheumatic Diseases.

AU sometimes precedes the symptoms of AS, and the risk for AU flares continues to increase after the time of AS diagnosis. Tumor necrosis factor (TNF) inhibitors have been demonstrated to reduce the incidence of acute AU. However, etanercept may not prevent AU to the same extent as infliximab or adalimumab, although data are conflicting and largely observational in nature.

Researchers examined whether different TNF inhibitors were associated with different rates of AU in patients with AS undergoing treatment with adalimumab, etanercept, or infliximab in a large registry study.

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Of 1365 patients from several registry databases, 406 received adalimumab, 354 etanercept, and 605 infliximab. The rates of AU within 2 years prior to the start of TNF inhibitor treatment were similar in all the groups.

In patients who did not have prior AU (n=1127), patients treated with etanercept were significantly more likely than patients treated with adalimumab or infliximab to develop AU within 2 years after starting TNF inhibitor treatment (hazard ratio [HR], 3.86 and 1.99, respectively).

High-Yield Data Summary

  • The risk of anterior uveitis increased 2- to 4-fold with etanercept compared with infliximab and adalimumab, respectively, within 2 years after starting TNF inhibitor treatment.

The rates of acute AU within 2 years post-treatment were similar with adalimumab and infliximab treatment.

“Among those treated with [etanercept], without an AU event in the 2 years prior to treatment start, the on-treatment rates were similar to the pretreatment rates overall for the [etanercept] group, possibly suggesting a lack of protective effect of [etanercept] on AU flares,” the researchers wrote.

Summary and Clinical Applicability

TNF inhibitors have been shown to decrease the risk of AU in patients with AS, although some data suggest that etanercept may not be as effective as other TNF inhibitors at preventing AU. Researchers found that the risk of AU was increased 2- to 4-fold with etanercept compared with infliximab and adalimumab, respectively, within 2 years after starting TNF inhibitor treatment.

“These results, in addition to previously published data on this topic, support the choice of another [TNF inhibitor other] than [etanercept] in patients with AS with a history of AU,” the researchers concluded.

Study Limitations

  • AU flares were defined based on ophthalmology visits for that indication, and it is unknown whether individual visits were for a new flare or for follow-up for a previous flare
  • This study was based on registry data, which may be limited by misclassified or missing data


Dr Lie has received personal fees from AbbVie, Bristol-Myers Squibb, Hospira, Pfizer and UCB. Dr Kristensen has received fees for speaking and consultancy from Pfizer, UCB, Roche, AbbVie, BMS, Novartis, Eli Lilly, Celgene, Biogen and MSD. Dr Jacobsson has received Advisory Board fees from AbbVie, Celegen, MSD, Novartis and UCB. Dr Askling has participated in advisory boards arranged by Lilly, AstraZeneca and Novartis but not received any personal remuneration.

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Lie E, Lindström U, Zverkova-Sandström T, et al. Tumour necrosis factor inhibitor treatment and occurrence of anterior uveitis in ankylosing spondylitis: results from the Swedish biologics register [published online March 2, 2017] Ann Rheum Dis. doi: 10.1136/annrheumdis-2016-210931 

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