Lupus nephritis B cell dilemma

Side effects profile

Do we need another pharmacologic agent for treatment of lupus nephritis? 

Kidneys may be affected in up to 60% of cases of lupus. About 1/3rd of such patients may end up with kidney failure. American College of Rheumatology recommends triple therapy for lupus nephritis (proliferative) – mycophenolate mofetil, glucocorticoids and a third agent). 

There have been encouraging results for an ideal 3rd candidate- Belimumab (an intravenous recombinant monoclonal IgG-1 lambda antibody) that inhibits B- cell activating factor OR voclosporin, a novel calcineurin inhibitor that works by modulating T- cell response. Randomized placebo-controlled trials with belimumab and with voclosporin have both shown that a combination therapy with mycophenolate and low dose steroids along with B-cell belimumab or T cell voclosporin had a better kidney outcome response with acceptable side effects profile compared to standard therapy alone. 

Thus the question is – is a 3rd agent- a deep B cell depletor (CD20) such as Obinutuzumab still needed? And where does it sit in the treatment paradigm of active lupus nephritis? 

Longer term data would be helpful as the current NEJM results from NOBILITY trial does not show us the eGFR comparison which will be much helpful. 

But one should emphasize that Obinutuzumab is not benign- the incidence of serious adverse events such as neutropenia, COVID 19 infection and pneumonia was significantly higher in Obinutuzumab group!