Study Shows TNF Inhibitors Prevent Relapse of Uveitis in Most Patients with Ankylosing Spondylitis

August 26, 2016
Ellen Kurek

Adalimumab, infliximab, and etanercept, reduced the number of uveitis relapses in a retrospective, long-term study of uveitis patients with HLA-B27-positive ankylosing spondylitis who had taken one of these biological agents for at least 1 year.

Although the main articular manifestation of ankylosing spondylitis (AS) is inflammation of the intervertebral joints, one of its main extra-articular manifestations is acute anterior uveitis. The prevalence of uveitis in AS patients varies depending on the patient population studied. However, a meta-analysis of 143 reports found that the pooled prevalence of uveitis in AS patients was 26%, and that this prevalence increased with alongside the duration of AS.

Human Leukocyte Antigen (HLA)-B27 is frequently found in AS patients and is the most common cause of acute anterior uveitis. In North America and Europe, the prevalence of HLA-B27 is approximately 8% to 10%, but the prevalence of the HLA-B27 allele in patients with acute anterior uveitis is much higher, ranging from 15% to 60%.

Most patients with HLA-B27-associated uveitis have acute or recurrent inflammation, but some may have chronic inflammation, defined as uveitis that lasts longer than 3 months or that requires long-term therapy. Chronic uveitis develops in approximately 5% to 19% of patients with HLA-B27-associated uveitis and is associated with a 7-fold increase in the risk of visual impairment. Moreover, poor control of inflammation has been associated with the development of ocular complications including vision loss.

Current guidelines recommend using biological agents to treat more severe or advanced uveitis. The anti-tumor necrosis factor alpha (anti-TNFα) agents adalimumab (Humira, Abbvie) and infliximab (Remicade, Janssen) are the biological agents most frequently used for uveitis. Etanercept (Enbrel, Amgen) has also been used, but it appears to be less effective in treating ocular inflammation than systemic inflammation.

To assess the long-term efficacy of these three anti-TNFα agents in treating uveitis in patients with HLA-B27 positive AS, a Korean team retrospectively reviewed the medical records of 143 such patients who visited Seoul St. Mary’s Hospital and had taken one of these three agents for at least 1 year. Results of the study are being published in the October, 2016, issue of the American Journal of Ophthalmology.

Mean patient age was 41 ± 13 years, and 97 patients (68%) were male. Mean follow-up was 71 ± 38 months. Study patients were divided into three groups on the basis of the anti-TNFα agent used.

For those with ocular inflammation at the onset of therapy, the number of days before improvement occurred was measured. Improvement occurred most rapidly in the adalimumab group (45 patients), in whom uveitis improved after 18 ± 6 days. In contrast, in the infliximab group (66 patients), uveitis improved after 24 ± 15 days, and in the etanercept group, it improved after 26 ± 18 days.

After treatment, 76% of patients did not experience a uveitis relapse. Absence of relapse was most common in the adalimumab group; relapse did not occur in 79% of this group, compared with 76% of the infliximab group and 68% of the etanercept group. In addition, the number of systemic medications could be safely reduced in 90% of study patients.

Minor side effects were observed in 28 patients. In 4 patients, tuberculosis developed, which led to discontinuation of therapy.

These results led the investigators to conclude the anti-TNFα agents studied were effective for treating uveitis and reducing the number of uveitis relapses in HLA-B27-positive AS patients. However, they warned that anti-TNFα therapy poses an increased risk of serious infections such as tuberculosis, which occurred in nearly 3% of the patients in their study, and that this risk continues to increase with prolonged use of anti-TNFα agents.