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Clinical Trial
. 2013 Feb;65(2):447-56.
doi: 10.1002/art.37785.

Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid

Bernard R Lauwerys  1 , Eric Hachulla, François Spertini, Estibaliz Lazaro, Christian Jorgensen, Xavier Mariette, Edwige Haelterman, Géraldine Grouard-Vogel, Bernard Fanget, Olivier Dhellin, Pierre Vandepapelière, Frédéric A Houssiau
Affiliations
Clinical Trial

Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid

Bernard R Lauwerys et al. Arthritis Rheum. 2013 Feb.

Abstract

Objective: We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE.

Methods: We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE.

Results: IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers.

Conclusion: These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted.

Trial registration: ClinicalTrials.gov NCT01058343.

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