Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet's disease with refractory uveoretinitis.
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.


CONCLUSIONS
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.
Ohno
Shigeaki
S
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-8638, Japan.
Nakamura
Satoshi
S
Hori
Sadao
S
Shimakawa
Machiko
M
Kawashima
Hidetoshi
H
Mochizuki
Manabu
M
Sugita
Sunao
S
Ueno
Satoki
S
Yoshizaki
Kazuyuki
K
Inaba
Goro
G
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001528:Behcet Syndrome / Q000150:complications* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab