The Filtered Fragments (OG Filtrate)

Joel Topf

Jennie Lin

Swapnil Hiremath

Special Guest

Brad Rovin GN God and second author from The Ohio State

Koyal Jain GN Specialist from UNC

Alfred Kim Rheumatologist from Washington University

Editing by

Simon Topf and Nayan Arora

The Kidney Connection written and performed by by Tim Yau

Show Notes

Joel’s monologue One of the most surprising facts of nephrology is that despite conventional wisdom that lupus nephritis is an antibody mediated disease, that over a decade ago, the LUNAR investigtors were unable to find a significant benefit when rituximab was added to conventional therapy. And this was after the equally negative phase 2 trial of rituximab, EXPLORER.

In fact, despite this finding rituximab has been able to burough its way into treatment of many nephrologists and rheumatologists as well as the KDIGO guidelines where it is suggested for patients with persistent disease activity or inadequate response to initial standard-of-care therapy.

This long conflict is now coming to an end. Obinutuzumab, a newer, better monoclonal antibody targeting the same CD20 that we grew to love with rituximab, but it has a number of advantages.

One. It is humanized antibody rather than a chimeric mouse-human antibody

Two. It’s cytotoxicity is not complement dependent an particular advantage if you want to deploy it ina disease where hypocomplementemia is a disease characteristic

Three, and most importantly, it causes stronger and deeper b-cell depletion than rituximab. Better B-cell depletion in the blood and tissue.

And this brings us to tonight’s topic, we had already seen the phase two results of obinutuzumab which, unlike EXPLORER, were positive, we will look at the phase three regency trial. This makes the third novel lupus nephritis drug in the last 4 years. We continue to remake glomerular nephritis.

LUNAR: Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study Pubmed

EXPLORER: Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial Pubmed

REGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis NEJM | NephJC

NOBILITY: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Annals of Rheumatic Disease

Comparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus Phase 3 program PubMed Central

Class 5 lupus nephritis is slow to respond Long-term Use of Voclosporin in Patients with Class V Lupus Nephritis: Results from the AURORA 2 Continuation Study ACR Meeting abstract

Tubular Secretions

Swap: Young Adult novel I Must Betray You by Ruta Sepetys (Amazon)

Koyal: Taekwondo (Wikipedia)

Jennie: these unprecedented times Trump NYT: Administration Freezes $1 Billion for Cornell and $790 Million for Northwestern, Officials Say

Al: Acquired Podcast

Brad: The Feather Thief by Kirk Wallace Johnson (Amazon)

Joel: Paradise on Hulu (Wikipedia)

FF 79 REGENCY, Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis