Anifrolumab achieves rapid and durable BICLA-response

Data from the phase 3 TULIP studies showed that treatment of systemic lupus erythematosus (SLE) patients with anifrolumab resulted in more British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) responses compared with placebo, starting at early timepoints and being sustained through week 52. Prof. Eric Morand (Monash University, Australia) who presented these studies, stated that rapid and durable BICLA response supports the clinical benefit of anifrolumab for patients with moderately to severely active SLE [1].

The human monoclonal antibody anifrolumab is a type I interferon (IFN) receptor antagonist, which has previously shown promising results in the phase 3 TULIP-2 and TULIP-1 trials in SLE [2,3]. Both TULIP-2 (anifrolumab n=180; placebo n=182) and TULIP-1 (anifrolumab n=180; placebo n=184) were randomised, double-blind, placebo-controlled trials which evaluated the efficacy and safety of anifrolumab (300 mg every 4 weeks) over 52 weeks in patients with moderately to severely active SLE who were receiving standard-of-care treatment [2,3]. BICLA responses on anifrolumab versus placebo at week 52 showed differences of 16.3% (95% CI 6.3-26.3; P=0.001; primary endpoint) and 16.4% (95% CI 6.7–26.2; secondary endpoint), respectively. However, optimal attributes of therapeutics for SLE include rapid onset and durability of response.

In this follow-up study, Morand et al. compared BICLA responses on anifrolumab versus placebo over time in both TULIP studies, and pooled data for early timepoints, for time to onset of BICLA response sustained to week 52, as well as for major and partial clinical response [1]. BICLA response was defined as all of the following: 1) reduction of baseline BILAG-2004 domain by at least 1 gradation and no worsening in other BILAG-2004 organ systems; 2) no worsening of disease activity (determined by SLE Disease Activity Index (SLEDAI)-2K and Physician Global Assessment (PGA); 3) no study treatment discontinuation; 4) no use of restricted medications beyond protocol-allowed thresholds [2,3]. Major clinical response was defined as all BILAG-2004 scores C or better at week 24, maintained through week 52, with no new A or B scores between weeks 24-52, whilst partial clinical response was defined as a maximum of 1 BILAG-2004 B score at week 24, maintained through week 52, with no new B domain scores through week 52. The majority of patients was young (median age pooled from both studies 42.6 years) and female (92.5%).

Results showed that at the first 3 assessments in TULIP-2 (at weeks 4, 8, and 12), numerically higher percentages of patients treated with anifrolumab (26.8%, 35.3%, and 42.9%, respectively) were classified as having a BICLA response compared with patients receiving placebo (21.3%, 21.6%, and 31.8%). A similar trend was observed in TULIP-1 with anifrolumab (23.3%, 34.2%, and 36.5%) versus placebo (18.3%, 23.2%, and 27.5%). The time to onset of BICLA response sustained through week 52 favoured anifrolumab in both TULIP-2 (HR 1.55; 95% CI 1.11-2.18) and TULIP-1 (HR 1.94; 95% CI 1.38-2.73). These data translate into an HR of 1.73 (95% CI 1.37-2.20) for the pooled data. In TULIP-2, 86 (47.8%) patients treated with anifrolumab had BICLA responses that were sustained through week 52 compared with 57 (31.3%) patients in the placebo group. Major clinical response was achieved by 22.1% of anifrolumab patients in TULIP-1 versus 15.8% of those on placebo, and 20.8% versus 10.9% in TULIP-2; pooled data showed a major clinical response rate of 21.5% for anifrolumab versus 13.4% for placebo. Partial clinical response was achieved in 45.4% of anifrolumab patients in TULIP-1 versus 40.2% of placebo patients, 46.8% versus 38.4% in TULIP-2, and 46.1% versus 39.3% in the pooled data. It was concluded that anifrolumab not only achieved more BICLA responders compared with placebo, but that the time of onset favoured anifrolumab as well.

1. 1. Morand EF, et al. Abstract P0003. EULAR E-Congress, 3-6 June 2020.
   2. Morand EF, et al. N Engl J Med. 2020;382:211–221.
   3. Furie RA, et al. Lancet Rheumatol. 2019;1:e208–e219.