Intensified treatment regimen of anifrolumab for lupus nephritis is promising

An intensified treatment regimen of anifrolumab showed superiority over placebo on several clinical endpoints for patients with active, proliferative lupus nephritis (LN) [1]. The results of the randomised, placebo-controlled, double-blind phase 2 TULIP-LN trial therefore encourage further efficacy and safety assessment of anifrolumab in this population.

Anifrolumab, a type 1 interferon (IFN) receptor-targeting antibody, has demonstrated benefits for patients with moderate-to-severe systemic lupus erythematosus (SLE) in prior phase 3 trials [2,3]. However, patients with active, proliferative LN were not included in these studies. Since up to 40% of patients with SLE develops LN, and LN could lead to glomerular and tubulointerstitial damage, further evaluation of the use of anifrolumab in this population is required. In addition, type 1 IFN signalling is involved in LN pathogenesis, providing another rationale for investigating anifrolumab in LN patients.

In the TULIP-LN phase 2 trial (NCT02547922), 147 patients with active proliferative LN were randomised 1:1:1 to anifrolumab basic regimen (300 mg intravenous every 4 weeks), anifrolumab intensified regimen (900 mg for 3 doses, 300 mg thereafter, intravenous every 4 weeks), or placebo (intravenous every 4 weeks) in addition to standard therapy. The primary endpoint was the difference in change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR) for combined anifrolumab regimens versus placebo at week 52.

The primary endpoint was not met: geometric mean change from baseline in 24-hour UPCR between placebo and the 2 regimens was not significantly different (P=0.905). Individually, no differences were observed between the 24-hour UPCR geometric mean ratio of placebo versus the basic regimen (1.10; 95% CI 0.61–1.99; P=0.741) and versus the intensified regimen (0.96; 95% CI 0.55–1.69; P=0.895). Numerical improvements of this measure over placebo were observed for both anifrolumab regimens at week 12 and week 24, and at week 36 for the intensified regimen. Pharmacokinetics exposure and pharmacodynamics exposure showed suboptimal results for the basic regimen group. Therefore, the authors focussed on the intensified regimen group for the secondary outcome measures.

Patients in the intensified regimen showed no difference in attained complete renal response (CRR; +14.3%, P=0.162). Nonetheless, a significant difference was observed for CRR with inactive urine sediments (+27.6%,  P=0.003). SLE Disease Activity Index (SLEDAI)-2K (-2.6 vs -1.3); Physician’s Global Assessment (-0.98 vs -0.66), and Patient Global Assessment (-16.7 vs -8.7) showed numerical benefits of the anifrolumab intensified regimen versus placebo. Finally, lupus serological tests showed numerical benefits of anifrolumab treatment: C3 improvements if C3 was low at baseline (median change -0.28 vs -0.14 g/L); and anti-dsDNA reductions (median change -73.2 vs -11.0 units/mL).

The safety profile was similar to that of non-renal SLE patients, which was provided in previous anifrolumab trials. Adverse events occurred in 93.8% of the anifrolumab-treated patients and in 89.8% of the placebo patients. There were respectively 10, 9, and 8 cases of serious adverse events in the basic regimen arm, intensified regimen arm, and the placebo arm. Herpes zoster occurred more often in anifrolumab recipients (16 cases) than in placebo patients (4 cases). Prof. David Jayne (University of Cambridge, UK) concluded that the results of this study support further investigation of the intensified regimen of anifrolumab in patients with active, proliferative LN.

1. Jayne D, et al. Randomized, Controlled; Phase 2 Trial of Type 1 IFN Inhibitor Anifrolumab in Patients With Active Proliferative Lupus Nephritis. POS0690, EULAR 2021 Virtual Congress, 2–5 June.
2. Furie RA, et al. Lancet Rheumatol. 2019;1(4):e208-19.
3. Morand EF, et al. N engl J Med. 2020;382(3):211-21.

 

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Posted on 2 August 20213 August 2021