Abstract 1315: MEDI-545, an anti-interferon alpha monoclonal antibody, shows evidence of clinical activity in systemic lupus erythematosus.
Authors:
DJ Wallace, M Petri, N Olsen, K Kirou, G Dennis, Y Yao, B Jallal, A Coyle, L Zeng, Lupus Interferon Skin Activity (LISA) Investigators, B White.
Background:
In SLE, plasmacytoid dendritic cells are activated (through toll-like receptors) by immune complexes to produce interferon. Interferon then activates myeloid dendritic cells that present antigen to T cells as well as make the B lymphocyte stimulator protein (BLyS). 50% of SLE patients have the interferon gene signature. SLE patients have elevated levels of interferon. Interferon alpha given to non autoimmune patients can cause a lupus-like illness. This clinical trial studied a monoclonal antibody against interferon alpha.
Methods:
This was a dose-finding study of 5 doses of the monoclonal antibody and placebo. In addition to disease activity, skin biopsies and photographs of SLE rashes were obtained. Several interferon-induced proteins were stained in the biopsies (HERCS, ISGIS, IP-10).
Results:
Clinical benefit: A SLEDAI score of 0 was obtained in 39% of active vs 12% of placebo (p=0.09). A PGA < 0.5 was achieved in 46.7% vs 18.8% (p=0.11). A flare (SELENA SLEDAI > 3) occurred in 3% of active vs 29% placebo (p=0.017). New steroid was prescribed to 6% of active vs 35% of placebo (p=0.0134). Skin biopsies showed an inhibition of interferon-induced proteins; the blood interferon signature was also inhibited.
Safety:
There was no immunogenicity.
Conclusion:
MEDI-545 showed proof of concept in that it inhibited the interferon signature AND it showed clinical efficacy in terms of disease activity, flares, and steroid sparing.
Editorial Comment:
Given this small study, the clinical benefit seen is very impressive. On patient at the highest dose (30 mg/kg) had benefit for over 2 ½ months! Questions to be addressed in subsequent trials will be whether the safety holds up – remembering that since this monoclonal blocks only IFN-alpha, leaving other Type 1 and Type 2 interferons alone, the hope is that there will not be an increase in serious infections.
