Long-term treatment with anifrolumab significantly increased the likelihood of achieving lupus low disease activity state (LLDAS) and remission as defined by the DORIS criteria in patients with moderate to severe systemic lupus erythematosus (SLE), according to a post hoc analysis published in Annals of the Rheumatic Diseases. These findings are based on a combined assessment of the TULIP-1, TULIP-2, and their long-term extension trials, which collectively tracked disease activity outcomes over a four-year period.
The analysis included 370 patients who received either intravenous anifrolumab 300 mg or placebo every four weeks for 52 weeks, followed by continued treatment in a three-year extension. At week 208, 37% of patients in the anifrolumab group achieved LLDAS compared to 17% in the placebo group, corresponding to an odds ratio (OR) of 2.7. Similarly, DORIS-defined remission was reached by 30% of patients on anifrolumab versus 18% on placebo (OR 1.9). Although the remission difference narrowly missed statistical significance (P = 0.07), the trend remained consistent across other time-based outcomes. Patients receiving anifrolumab reached their first LLDAS and DORIS states more quickly than those on placebo, with hazard ratios of 1.6 and 1.5, respectively. Notably, the cumulative time and percentage of time spent in LLDAS or DORIS were significantly higher in the anifrolumab group (P = 0.0004 and P = 0.003, respectively), underscoring sustained disease control over the long term.
Traditional treatment options for SLE primarily include glucocorticoids and immunosuppressive agents. However, these therapies are associated with an increased risk of serious adverse effects, including infections and increased mortality. As a result, there is a pressing need to develop targeted biological therapies to more effectively manage the disease. Type I interferons play a crucial role in the pathogenesis of SLE, with elevated type I interferon activity observed in over 60% of patients. This increased interferon signature is strongly associated with increased disease activity, as reflected by a significant positive correlation with the SLE Disease Activity Index (SLEDAI) score.
Anifrolumab is a fully human, effector-null IgG1κ monoclonal antibody that targets subunit 1 of the type I interferon receptor (IFNAR1), effectively blocking all type I interferon-mediated signaling. Structural and molecular docking studies have demonstrated that anifrolumab sterically hinders the binding of type I interferons to IFNAR1. To eliminate Fc-mediated effector functions—such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity—anifrolumab was engineered with a triple mutation (L234F, L235E, P331S) in its heavy chain, minimizing its interaction with Fc gamma receptors (FcγRs).The 52-week Phase 3 TULIP-1 and TULIP-2 trials provided key evidence supporting the approval of anifrolumab for the treatment of moderate to severe SLE. Post hoc analyses of these trials revealed that patients receiving anifrolumab achieved higher rates of LLDAS and clinical remission compared to those receiving standard therapy alone.
These findings reinforce LLDAS and DORIS as practical treat-to-target endpoints in SLE management, with anifrolumab offering a viable path to sustained low disease activity and remission. The data suggest that incorporating anifrolumab into standard therapy could alter the long-term trajectory of disease progression and organ damage in patients with SLE.
References
- Morand EF, van Vollenhoven R, Furie RA, Kalunian KC, Manzi S, Abreu G, et al. LLDAS and remission attainment with anifrolumab treatment in patients with systemic lupus erythematosus: results from the TULIP and long-term extension randomised controlled trials. Ann Rheum Dis. 2025 May;84(5):777-788.
- Liu Z, Cheng R, Liu Y. Evaluation of anifrolumab safety in systemic lupus erythematosus: A meta-analysis and systematic review. Front Immunol. 2022 Sep 23;13:996662.
- Riggs JM, Hanna RN, Rajan B, Zerrouki K, Karnell JL, Sagar D, et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Sci Med. 2018 Apr 5;5(1):e000261.