medwireNews: Findings from the phase 2 TULIP-LN trial suggest that add-on treatment with an intensified regimen of anifrolumab, a type I interferon receptor inhibitor, may improve some outcomes for patients with lupus nephritis (LN).
However, the primary endpoint of the study was not met, with no significant difference in 24-hour urine protein:creatinine ratio (UPCR) improvements from baseline to 1 year among participants treated with anifrolumab versus placebo.
Discussing the background to their trial, Catharina Lindholm (AstraZeneca R&D, Gothenburg, Sweden) and co-investigators explain that high type I interferon gene signatures are present in more than 80% of people with LN and associated with disease activity and treatment failure.
“Therefore, there is scientific rationale to support anifrolumab […] as a potential LN treatment option,” they say, noting that the drug has been investigated previously for the treatment of systemic lupus erythematosus (SLE) in the TULIP-1 and TULIP-2 trials.
TULIP-LN included 145 patients with active, biopsy-proven, class III/IV LN who were randomly assigned to receive 48 weeks of anifrolumab every 4 weeks at the standard SLE dose (300 mg) or an intensified dose (900 mg for the first three doses and 300 mg thereafter), or to receive placebo, in addition to ongoing standard therapy. Participants had a median age of approximately 34 years and the majority (73.1%) had class IV disease.
Lindholm and team report that the average 24-hour UPCR improved from 3.10 mg/mg at baseline to 0.92 mg/mg in the combined anifrolumab group (n=96), and from 3.71 to 1.05 mg/mg in the placebo group (n=49), translating into a nonsignificant geometric mean ratio of 1.03 for anifrolumab versus placebo.
The researchers say that this result can be explained by “suboptimal anifrolumab exposure” in the standard dosing group, which “was likely related to increased clearance associated with proteinuria in LN.”
Indeed, when the anifrolumab groups were analyzed separately, the “anifrolumab [intensified regimen] was numerically superior to placebo for several clinically relevant endpoints, whereas the [standard regimen] was not,” they add.
For example, the proportion of patients with a complete renal response (CRR) was numerically higher with the intensified anifrolumab regimen versus placebo (45.5 vs 31.1%), as was the proportion of patients achieving sustained glucocorticoid dose reductions (55.6 vs 33.3%). CRR was defined as 24-hour UPCR of 0.7 mg/mg or lower, estimated glomerular filtration rate of at least 60 mL/min per 1.73 m2 or no decrease of 20% or greater from baseline, no discontinuation of study drug, and no use of restricted medications.
These findings suggest that the intensified anifrolumab schedule “is a more suitable dosing regimen than the [standard SLE dose] to carry forward into future clinical investigations of anifrolumab to treat patients with active LN,” write the authors in the Annals of the Rheumatic Diseases.
They say that the safety profile of anifrolumab in TULIP-LN “was generally consistent with that seen in SLE without active renal disease,” including a higher incidence of herpes zoster with anifrolumab than placebo.
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