Obinutuzumab Efficacy in Active Lupus Nephritis Save

A phase 3, randomized controlled trial of an anti-CD20 monoclonal antibody, obinutuzumab, was shown to be effective and safe in patients with active lupus nephritis.

 

Obinutuzumab is a humanized, anti-CD-20 mAb, currently approved for use in chronic lymphocytic leukemia and follicular lymphoma.  It previously showed encouraging results in a phase II trial in patients with SLE. 

 

The New England Journal of medicine has published the results of a 277 patient trial wherein adults with biopsy-proven active lupus nephritis were randomized to receive either placebo or obinutuzumab (one of two dose schedules-1000 mg on day 1 and at weeks 2, 24, 26, and 52, with or without a dose at week 50) . All patients remained on standard background therapy with mycophenolate mofetil, along with oral prednisone at a target dose of 7.5 mg per day by week 12 and 5 mg per day by week 24. The primary end point was a complete renal response (CRR) at week 76, defined by a urinary protein-to-creatinine ratio of less than 0.5 (with protein and creatinine both measured in milligrams), an estimated glomerular filtration rate of at least 85% of the baseline value, and no intercurrent event (i.e., rescue therapy, treatment failure, death, or early trial withdrawal). 

 

Overall, 135 were given obinutuzumab and 136 placebo. A complete renal response at week 76 was seen in: 

More patients on obinutuzumab were able to be on prednisone 7.5 mg per day or less between weeks 64 and 76 than placebo (42.7% vs. 30.9%; P=0.04).

 

A urinary protein-to-creatinine ratio lower than 0.8 was also more common with obinutuzumab than placebo (55.5% vs. 41.9%; P=0.02). 

 

There were no unexpected safety signals were identified, but more serious adverse events occurred with obinutuzumab (mostly infections and COVID-19), 

Obinutuzumab plus standard therapy, appears to be effective in adults with active lupus nephritis. 

(Funded by F. Hoffmann–La Roche; REGENCY ClinicalTrials.gov number, NCT04221477.)