乌鸦传媒

SAN DIEGO -- Treatment with the B-cell depleting agent obinutuzumab (Gazyva) helped patients with lupus nephritis avoid the most serious adverse outcomes, according to a post hoc analysis of randomized trial data.

Among 125 patients assigned to obinutuzumab or placebo, risk of a composite of unfavorable outcomes was reduced 60% with the active drug, reported Brad H. Rovin, MD, of The Ohio State University in Columbus, and colleagues .

Rates of individual adverse outcomes were lower by up to 90%, the researchers indicated. The study is also to be presented at the American College of Rheumatology's annual meeting that starts here Friday.

Obinutuzumab is only for treating hematologic malignancies, but its manufacturer, Roche's Genentech unit, has been seeking additional indications insofar as B cells are at the root of many autoimmune and inflammatory diseases. The drug is massively more potent than the first-in-class agent rituximab (Rituxan). ClinicalTrials.gov with obinutuzumab, many in non-cancerous conditions.

The new study drew on data collected for the firm's phase II NOBILITY trial, first reported in 2020, in which the primary finding was that obinutuzumab effectively reduced markers of lupus nephritis relative to standard care. Rovin and colleagues (who included several Genentech and Roche employees) wanted more detail on whether the treatment could also preserve near-normal renal function. One of the things that makes lupus nephritis a feared complication of systemic lupus erythematosus is that these bouts of renal inflammation often leave patients with permanently impaired function.

NOBILITY enrolled 125 patients with active lupus nephritis, randomizing them 1:1 to obinutuzumab or placebo, in both cases added to standard treatment with steroids and mycophenolate mofetil. All were included in the new analysis.

The primary endpoint was a composite of three adverse outcomes: lack of treatment response, doubling in serum creatinine, or all-cause death. Other endpoints included lupus nephritis flare, declines in estimated glomerular filtration rate (eGFR) of 30% and 40%, and the rate of eGFR decline in serial measurement.

By the trial's end, about 40% of the placebo group had experienced one of the composite endpoint events, versus less than 20% of those on obinutuzumab; that translated to a hazard ratio of 0.40 (95% CI 0.20-0.80).

A similar reduction was seen in rates of lupus nephritis flare (HR 0.43, 95% CI 0.20-0.95). Risk of 30% and 40% decline in eGFR was lower by 80% and 91%, respectively -- only five patients receiving obinutuzumab saw a 40% decline by week 104. Decreases over time in eGFR were smaller by 4.10 mL/min/1.73 m²/year with obinutuzumab relative to placebo.

Rovin and colleagues also found that 38% of the obinutuzumab group maintained complete renal responses at week 104 while also taking no more than 7.5 mg/day of prednisone, compared with 22% in the placebo group, but this just missed statistical significance (P=0.06).

The researchers cautioned that these analyses were not prespecified in the original protocol, and consequently were underpowered for the selected endpoints. The group promised to repeat them in a now underway in patients with lupus nephritis, with initial results expected late next year.

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