Transcript Title of article - JAMA Ophthalmology

Multicenter Study of Infliximab for
Refractory Uveoretinitis in Behçet Disease
Okada AA, Goto H, Ohno S, Mochizuki M; Ocular Behçet’s Disease
Research Group of Japan. Multicenter study of infliximab for refractory
uveoretinitis in Behçet disease. Arch Ophthalmol. 2012;130(5):592-598.
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Introduction
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Behçet disease affected more than 17 000 individuals in Japan in 2008 and
represented the cause of uveitis in roughly 6% of new patient referrals to
specialty clinics.
Patients who have Behçet disease with active uveitis have been shown to
have increased tumor necrosis factor production by peripheral monocytes
compared with patients without active uveitis or control subjects.
Infliximab, a chimeric monoclonal antibody against tumor necrosis factor,
has been shown to be clinically effective in several autoinflammatory
conditions and was officially approved in Japan for the specific indication of
refractory uveoretinitis in patients with Behçet disease.
The aim of this study was to describe the effects of infliximab on uveitis in
patients with Behçet disease during the first year of treatment.
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Methods
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Prospective collection of clinical data was mandated by the Japanese
Ministry of Health, Labour, and Welfare for this indication.
Data were collected from patients who commenced infliximab therapy
between January 26, 2007, and August 23, 2008, at 8 participating tertiary
centers.
All patients had uveoretinitis refractory to immunosuppressive therapy or
were judged to be intolerant of such therapy.
After medical clearance, infliximab at the approved dose of 5 mg/kg was
infused at weeks 0, 2, and 6 and every 8 weeks thereafter. Concomitant
therapy was left to physician discretion.
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Methods
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Study Limitations:
– Of 97 eligible patients, data were obtained for only 63 patients.
– Efficacy and severity ratings were not defined.
– Only inflammatory attacks observed at clinic visits were counted. Thus,
there may have been underreporting of asymptomatic or mild attacks
that did not prompt the patient to seek examination.
– The infliximab dosing was fixed, and some patients may require larger
or more frequent doses.
– The effect of concomitant immunosuppressive therapy was not
evaluated.
– A follow-up of 1 year may be inadequate to fully assess the efficacy and
safety of infliximab therapy in Behçet disease.
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Results
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Among the 63 patients, 56 (89%) were male and 44 (70%) were aged 24 to
44 years.
A total of 34 episodes of adverse effects occurred in 29 patients (46%),
including 3 episodes of infusion reactions. None were serious.
Of note, 1-year efficacy was assessed after excluding 15 patients who had
previously received infliximab or in whom data were incomplete.
At 1 year, the uveoretinitis:
– Had improved in 69% (33 of 48 cases).
– Had improved somewhat in 23% (11 of 48 cases).
– Was unchanged in 8% (4 of 48 cases).
– Had worsened in no patients.
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Results
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The mean number of ocular attacks per 6-month period decreased from
2.66 at baseline to 0.44 during months 1 through 6 and to 0.79 during
months 7 through 12.
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Among 48 patients, 21 (44%) had no ocular attacks during the 1-year period.
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The mean best-corrected visual acuity improved from 0.736 logMAR at
baseline to 0.616 logMAR at the end of 1 year (P = .01).
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Results
Efficacy of Infliximab by Location and Severity of Ocular Inflammatory Attacksa
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Comment
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The use of infliximab for refractory uveoretinitis in Behçet disease in Japan
represents the first regulatory agency–approved use of a biologic agent for
any uveitis indication.
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This multicenter study concluded overwhelmingly good safety and efficacy
for this treatment in a large number of patients, although these conclusions
must be interpreted with the study limitations in mind.
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Further evaluation of longer follow-up, the effect of concomitant
immunosuppressive agents, and a scheme for severity grading is currently
under way.
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Comment
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The utility of biologic agents in various types of uveitis remains unclear.
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Biologic agents have potentially severe adverse effects and are extremely
expensive.
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From a public policy perspective, the utility of these agents requires careful
scrutiny.
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Contact Information
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If you have questions, please contact the corresponding author:
– Annabelle A. Okada, MD, Department of Ophthalmology, Kyorin
University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo
181-8611, Japan ([email protected]).
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