Efficacy, Safety, and Pharmacokinetics of Multiple Administration of Infliximab in Behçet's Disease with Refractory Uveoretinitis

SHIGEAKI OHNO, SATOSHI NAKAMURA, SADAO HORI, MACHIKO SHIMAKAWA, HIDETOSHI KAWASHIMA, MANABU MOCHIZUKI, SUNAO SUGITA, SATOKI UENO, KAZUYUKI YOSHIZAKI, and GORO INABA

ABSTRACT.

Objective. Behçet's disease (BD) with uveoretinitis is a chronic refractory disease accompanied by ocular attacks. As the decrease in visual acuity due to ocular attack is seriously life-threatening, development of a new drug is anticipated.

Since tumor necrosis factor-a (TNF-a) is involved in the symptoms of BD, particularly the activity of ocular symptoms, suppression of TNF-a might be effective in treating BD with uveoretinitis. We conducted a clinical trial of infliximab, an anti-TNF-a chimeric monoclonal antibody, in patients with BD.

Methods. In this open label trial, the efficacy, safety, and pharmacokinetics of repeated administration of infliximab were evaluated in 13 patients with BD accompanied by refractory uveoretinitis. Infliximab was administered 4 times at Weeks 0, 2, 6, and 10 at doses of either 5 or 10 mg/kg by intravenous drip infusion. Frequency of ocular attacks was used as the primary index for evaluation of efficacy, with visual acuity and extraocular symptoms as secondary indices.

Results. The mean numbers of ocular attacks, converted to frequency per 14 weeks, were 3.96 times for the 5 mg/kg group and 3.79 times for the 10 mg/kg group during the observation period. Following treatment with infliximab, they decreased to 0.98 times and 0.16 times, respectively. A serious adverse event, tuberculosis, was observed in one case in the 10 mg/kg group. Serum infliximab concentration increased with dosage.

Conclusion. Administration of infliximab in patients with BD with refractory uveoretinitis suppressed the frequency of ocular attacks, and multiple administration was well tolerated, suggesting that infliximab is effective for this condition. (J Rheumatol 2004;31:1362-8)

Key Indexing Terms:

BEHÇET'S DISEASE
REFRACTORY UVEORETINITIS
ANTI-TUMOR NECROSIS FACTOR-a ANTIBODY
CLINICAL STUDY

---

From the Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo; Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama; Department of Ophthalmology, Tokyo Women's Medical University; Department of Ophthalmology, Faculty of Medicine, University of Tokyo; Department of Ophthalmology, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo; Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki; Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Osaka; and Department of Internal Medicine, Jinkokai Hospital, Atsugi, Japan.

S. Ohno, MD, PhD, Professor, Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine; S. Nakamura, MD, PhD, Lecturer, Department of Ophthalmology, Yokohama City University School of Medicine; S. Hori, MD, PhD, Professor; M. Shimakawa, MD, PhD, Lecturer, Department of Ophthalmology, Tokyo Women's Medical University; H. Kawashima, MD, PhD, Associate Professor, Department of Ophthalmology, Faculty of Medicine, University of Tokyo; M. Mochizuki, MD, PhD, Professor; S. Sugita, MD, PhD, Teaching Assistant, Department of Ophthalmology, Faculty of Medicine, Tokyo Medical and Dental University; S. Ueno, MD, PhD, Professor, Department of Ophthalmology, St. Marianna University School of Medicine; K. Yoshizaki, MD, PhD, Professor, Department of Medical Science I, School of Health and Sport Sciences, Osaka University; G. Inaba, MD, PhD, Department of Internal Medicine, Jinkokai Hospital.

Address reprint requests to Dr. S. Ohno, Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-Ku, Sapporo, 060-8638, Japan.

Submitted June 10, 2003; revision accepted January 29, 2004.

---