Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial

Abstract

Objective: To characterise the safety and efficacy of anifrolumab in active lupus nephritis (LN) through year 2 of the phase II randomised, double-blind Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-LN trial (NCT02547922) of 2 anifrolumab dosing regimens versus placebo.

Methods: Patients received intravenous anifrolumab 900 mg for the first 3 doses followed by 300 mg anifrolumab (intensified regimen (IR)), 300 mg anifrolumab (basic regimen (BR)) or placebo every 4 weeks throughout. To continue into Year 2, patients must have achieved at least partial renal response and a glucocorticoid tapering target.

Results: Of 147 randomised patients, 101 completed Year 1 study treatment; of these, 75 (74%) continued into Year 2 (anifrolumab IR: n=29, BR: n=23 and placebo: n=23). During Year 2, 72% of patients reported ≥1 adverse event (AE); serious AEs were reported in 6.9%, 8.7% and 8.7% of patients (anifrolumab IR, BR and placebo, respectively); 3 patients discontinued treatment due to an AE (anifrolumab IR: n=2 and placebo: n=1) and herpes zoster was reported in 2 patients (anifrolumab IR: n=1 and BR: n=1). The study was ongoing at the start of the pandemic, but no COVID-19 cases were reported. Of the 145 patients receiving treatment, more patients on the IR attained complete renal response at Week 104 compared with those on BR or placebo (27.3% vs 18.6% and 17.8%) and simultaneously achieved sustained glucocorticoid tapering (IR: 25.0%; BR: 18.6% and placebo: 17.8%). The improvements in estimated glomerular filtration rate were numerically larger in both anifrolumab groups versus placebo.

Conclusions: The safety and tolerability profile through Year 2 of TULIP-LN was generally consistent with Year 1, with promising efficacy results for the anifrolumab IR regimen. Collectively, the results support further investigation of an anifrolumab intensified dosing regimen in larger populations of patients with active proliferative LN.

Trial registration number: NCT02547922.

Keywords: autoimmune diseases; lupus nephritis; therapeutics.

Figure 1

Patient disposition for the first and second years of the TULIP-LN study. *Percentages calculated using the full analysis set. ^†Percentages calculated using the second-year population (patients who continued into the second year). AE, adverse event; BR, basic regimen; IR, intensified regimen; TULIP, Treatment of Uncontrolled Lupus via the Interferon Pathway.

Figure 2

Efficacy end points over time. Analyses were conducted excluding patients from France and Italy. All data after discontinuation were excluded from the analysis. (A) CRR required 24-hour UPCR ≤0.7 mg/mg, eGFR ≥60 mL/min/1.73 m² or no decrease ≥20% from baseline, no treatment discontinuation and no use of restricted medications. The response rates were calculated with a weighted Cochran-Mantel-Haenszel controlling for stratification factors; percentages are based on the number of patients in the analysis, so the denominator remained the same each week (anifrolumab IR: n=44; anifrolumab BR: n=43; placebo: n=45). Non-responder imputation was applied in case of missing data in any of the CRR components. (B) Mean cumulative proteinuria (area under the curve in UPCR standardised by the expected follow-up time) was assessed using analysis of covariance controlling for baseline UPCR and stratification factors. Error bars represent SE. (C) Non-renal SLEDAI-2K change from baseline is expressed as least squares means which were calculated using a mixed model for repeated measures, controlling for stratification factors. Missing data for continuous end points were modelled under the missing-at-random assumption within the mixed model for repeated measures model. BR, basic regimen, CRR, complete renal response; eGFR, estimated glomerular filtration rate; IR, intensified regimen; LS, least squares; n, number of subjects in the treatment group; SLEDAI-2K, SLE Disease Activity Index 2000; UPCR, urine protein-creatinine ratio.