Comment on: Rapid Efficacy of Anifrolumab Across Multiple Subtypes of Recalcitrant Cutaneous Lupus Erythematosus Parallels Changes in Discrete Subsets of Blood Transcriptomic and Cellular Biomarkers
Comment by: Professor Edward Vital, Associate Professor in Systemic Lupus Erythematosus at University of Leeds. Chair of BILAG and the Lupus Forum.
Anifrolumab has been shown to be effective in SLE. However, we have had less information on how this fits into a strategy of other treatments for lupus or on specific manifestations. These details can be important to targeted therapies. For example, it was noted in the past that many types of skin lupus did not respond to rituximab therapy therapies and in fact even develop new lesions in the absence of B cells. The most striking sample of this was discoid lupus. Here, anifrolumab was given to group of resistant cutaneous lupus patients. As well as their cutaneous lesions, these patients were all at least ANA positive, although many did not have other active organs. The results were quite striking; all of the patients treated responded, despite failing up to 15 different therapies in the past. Most of them were in complete remission within a few weeks of the first infustion. This marked difference in response with anifrolumab versus their previous therapies therefore emphasises that severely resistant disease may be explained by the similar modes of action of many older therapies (mostly targeting circulating lymphocytes), and may require an alternative mechanism targeting interferons or other cytokines generated in the lesions themselves. This study was also analysed for a range of circulating biomarkers including flow cytometry and gene expression panels covering the major transcriptomic changes known in SLE. Interestingly many of these biomarkers did not change despite the fact that the skin responded so well. The interferon signature was significantly reduced overall although some interferon stimulated genes’ expression did not fall. The other gene expression panels did not change. Circulating cell subsets, which were a baseline, did not change. The one exception was to intermediate monocytes. Again, these modest improvements in blood biomarkers despite marked improvement in skin lesions suggest that the mode and site of action of this therapy differs. In summary, anifrolumab is effective in disease that is resistant to B cell targeted therapies and is effective in discoid, acral and subacute morphologies of cutaneous lupus.