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From Arsenic to Interferon – Do We Finally Have Good Targets for the Treatment of Lupus?

November 11 2015 6:14 AM ET via RheumReports RheumReports

I was excited to attend the novel therapeutic session for lupus this afternoon.  It's the one place where the notable "who's who" of international lupus experts will sit together to avoid the alternative of sitting on the floor in this crowed room. 

A dizzying array of targets, some new and some old, were presented at this session. 

Dr. Stohl presented data supporting the results of subcutaneous belimumab in the Phase 3 BLISS-SC randomized, double-blind, placebo-controlled trial. Key points from this study included that more patients achieved the primary endpoint of the SRI4 response at week 52 than placebo (OR 1.64; 95% CI 1.22-2.8), severe flares were reduced by 50% over 52 weeks, and there was a trend to greater steroid-sparing in the belimumab group. This is a big deal because currently belimumab is IV, which requires an infusion centre, staffing and IV access.  Introducing a SC formulation of belimumab has practical and economic implications for the patient and health care system. SC belimumab must still undergo FDA approval (even though the IV formulation is approved), but expect to hear more about it with these results. 

If you are getting bored – read on – the next treatment discussed was arsenic! The Lupsenic trial, a proof of concept phase 1/2a, open-label, multicentre French study in adult lupus patients, demonstrated acceptable safety and tolerability while demonstrating short-term clinical efficacy. How does this work without killing the patient? Well it's quite different from an Agatha Christie novel! It was approved 10 years ago for acute promyelocytic leukemia, and has already been shown to reduce lymphoproliferation, suppress skin lesions, and prevent inflammatory infiltrates in lungs and kidneys in lupus animal models, while inhibiting immune complex deposition. Larger clinical trials may follow.

The star of the show was anifrolumab – a fully human IgG kappa monoclonal antibody directed against interferon alpha. A phase 2b randomized, placebo-controlled trial in lupus evaluated the efficacy of two doses of the drug administered IV once monthly in 305 adult, seropositive, moderate to severe SLE patients. For once, the odds ratios for patients on the medication (especially the lower dose of 300 mg) were in the range of 2/3/4 depending on the analysis that was employed. Patients with higher interferon alpha gene signatures had greater improvements in the various endpoints, which included achieving the SRI4, steroid dose reduction, and maintenance of response. Notable improvements in skin lupus using the CLASI score were also reported. 

While future work is clearly needed for all the medications mentioned, the atmosphere of optimism was a great change from past years at ACR for the lupus sessions. 


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About the Author

Dr. Stephanie Keeling
Dr. Stephanie Keeling

Dr. Stephanie Keeling is an Associate Professor at the University of Alberta. Her research interests include lupus and connective tissue disorders.

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