Antibody Development an Obstacle in Treating Uveitis with Humira

A Spanish research team found an association between testing positive for antibodies to adalimumab (Humira) and a worse outcome of uveitis, but only in those who tested positive permanently. They also found that this association correlated with undetectable trough levels of Humira.

Although adalimumab (Humira/AbbVie) is a fully human monoclonal antibody, antibodies to it develop in 5% to 54% of patients treated with it, depending on the disease. Moreover, the development of these antibodies has been associated with decreased clinical efficacy and adverse effects.

Because the formation of complexes between anti-Humira antibodies and Humira itself increase clearance and reduce serum levels of Humira, clinicians can optimize therapy by monitoring levels of Humira and antibodies to it in serum. However, until recently, appropriate trough levels of Humira and the rate of formation of antibodies to it in uveitis patients have been unclear, in part because the U.S. Food and Drug Administration has not approved Humira for use in treating uveitis.

Nevertheless, the off-label use of Humira to treat refractory forms of noninfectious immune-mediated uveitis has produced encouraging results in many cases. And good-quality evidence supports the use of Humira in uveitis associated with spondyloarthropathy, HLA-B27, or juvenile idiopathic arthritis. Yet some patients with these conditions never respond to Humira or stop responding to it over time, and the development of antibodies against Humira may explain many of these treatment failures.

To determine the rate of immunogenicity induced by Humira and its relation with drug serum levels and clinical responses in patients with noninfectious uveitis, a Spanish team did a prospective observational study at a single referral center. The study enrolled 25 consecutive patients who were about to initiate therapy with Humira, 40 mg every other week, for active noninfectious uveitis resistant to conventional therapy. The study was done by Dr. Miguel Cordero-Coma and colleagues at the University Hospital of León in León, Spain.

Patients were evaluated before therapy was initiated and after 4, 8, and 24 weeks of treatment. At these time points, the investigators measured change in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and leakage on retinal angiograms. They also measured serum trough levels of Humira and antibodies to it.

The investigators found that nearly three-quarters (72%, or 18/25) of those studied responded to Humira; 44% (11/25) had a complete response and 28% (7/25) had a partial response. The other 28%, however, had no response. They also found that median trough serum levels of Humira were higher in responders than in non-responders (P < 0.001).

Antibodies to Humira developed in 32% of patients (8/25) at some point in the 24-week study. Four of these patients permanently tested positive for anti-Humira antibodies, and the other four tested positive only transiently.

In all patients with permanent antibody positivity, trough levels of Humira became undetectable (P < 0.001). In contrast, in those with transient antibody positivity, the investigators found no correlation between antibody titers and trough levels of Humira.

Moreover, the investigators only found an association between antibody positivity and worse outcome of uveitis in those with permanent antibody positivity. They also found that this association correlated with undetectable trough levels of Humira (P = 0.014).

Finally, the investigators noted that Humira immunogenicity was more common in patients with uveitis associated with a systemic disease. Nevertheless, they also noted that concomitant therapy with an immunosuppressant did not protect patients from forming antibodies to Humira.

The study, “Adalimumab for treatment of noninfectious uveitis,” was published in the December, 2016, issue of Ophthalmology.

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Adalimumab: Efficacy and Adverse Effects for Patients with Active Noninfectious Uveitis