Background/Purpose: Infliximab (IFX) suppresses ocular attacks in Behcet’s disease (BD) with uveitis, resulting in favorable long-term visual prognosis. However, some patients had ocular attacks which accumulate one or two weeks before the next IFX infusion, suggesting that the efficacy of IFX depends on the concentration. This study investigates IFX through levels and antibody toward IFX (ATI) in BD patients receiving IFX and analyzes the relationship of the pharmacokinetics with clinical efficacy and safety.

Methods: We retrospectively examined clinical courses of 20 BD patients (female 7, male 22 age 41.9 + 14.4 yo) who met the Japanese revised Behcet’s disease Diagnositic criteria (2003) and received IFX because of refractory uveitis to conventional therapies including cyclosporine A. In principle, immunosuppressants were discontinued before introduction of IFX therapy. In the original regimen, IFX (5mg/kg) was given at 0, 2, 6 week, and thereafter every 8 weeks, but the intervals were shortened to 5 weeks after major ocular attacks occurred. The blood samples were drawn prior to the next infusion. IFX concentrations and ATI in the sera were determined by ELSIA.

Results:  Mean duration was 6.4 + 5.8 years from the disease onset to initiation of infliximab therapy. A. Duration of IFX was 7 to 80 months. The therapy was discontinued in 2 patients because of infusion reaction and/or insufficient efficacy. Frequencies of ocular attacks (/6 months) were 2.6 + 2.1 and 0.4 + 0.5 before and after therapy, indicating that IFX suppresses ocular attacks significantly. During the therapy, total 29 ocular attacks occurred at 6.87 + 1.12 weeks after the last infusion, 1.43 + 1.53 weeks before the next infusion. The infusion interval was shortened from 5 to 7 weeks in 8 patients who experienced major ocular attacks. Thereafter, frequency of ocular attacks was reduced from 0.84 to 0.37/6months, while that was 0.10 in patients who continued to receive the infusions every 8 weeks. The mean IFX through level was 5.0 + 6.1 µg/ml but it was undetectable (less than 0.1µg/ml) in 7 patients. Of the 7 patients, 3 had recent ocular attacks, 6 showed extraocular symptoms, 6 had infusion reaction, and 6 had ATI. Shortening the infusion interval was associated with increased through level, leading to another remission in a patient. Besides 6 patients, ATI was also positive in one patient who had infusion reaction but no ocular attacks. Three of 4 patients who required admission due to infusion reaction were positive for ATI.

Conclusion: The present study suggests that low IFX trough level is also associated with ocular attacks, extraocular manifestations, and ATI, which is partially responsible for serious infusion reaction. Therefore, shortening the infusion interval and concurrent usage of immunosuppressants appear reasonable strategies to circumvent the issues.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunogenicity-of-infliximab-modulates-efficacy-and-safety-in-behcets-disease-patients-with-uveitis/