Anifrolumab Increases Odds of Earlier, Sustained Low Disease Activity vs Placebo in Lupus
Patients with systemic lupus erythematosus receiving anifrolumab are more likely to achieve earlier, more frequent and longer low disease activity, compared with those taking placebo, according to data.
“Deployment of [treat-to-target (T2T)] approaches in clinical practice also requires the existence of therapies that result in attainment of such target states,” Eric F. Morand, MD, of the Center for Inflammatory Diseases at Monash University, in Australia, and colleagues wrote in the Annals of the Rheumatic Diseases. “In the phase 3 Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-2 trial, efficacy of anifrolumab, a monoclonal antibody directed to the type I interferon (IFN) receptor, was demonstrated using the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response.”
Analysis
To analyze the attainment of lupus low disease activity state (LLDAS) in patients with SLE receiving anifrolumab (Saphnelo, AstraZeneca), Morand and colleagues conducted a post-hoc analysis of the phase 3 TULIP-1 and TULIP-2 trials. Both were studies investigating patients aged 18 to 70 years with moderate to severe disease, randomized patients to receive either anifrolumab or placebo. Additionally, all patients demonstrated an SLE disease activity index 2000 score of 6 or more, a clinical SLEDAI-2k score of 4 or more and an organ domain score of 1 or higher. Glucocorticoid tapering was encouraged throughout the studies, according to the researchers.
The current analysis pooled results from TULIP-1 and TULIP-2, including all patients from both studies who received either placebo or anifrolumab 300 mg. However, patients treated with anifrolumab 150 mg were excluded because this dose was not present in both TULIP studies. The researchers assessed the cumulative time patients spent in LLDAS at 20%, 50% and 70% of study period. They examined patients who acheived sustained LLDAS between trial visits and the time taken to reach initial LLDAS.
The pooled analysis included a total of 819 patients. Of those, 25% achieved LLDAS at week 52. According to the researchers, 30% of patients who received anifrolumab achieved LLDAS, compared with 19.6% of patients who received placebo (OR = 1.8; 95% CI, 1.3-2.5). In addition, patients who received anifrolumab were more likely to achieve LLDAS earlier than patients receiving placebo (HR = 1.76; 95% CI, 1.35-2.3), as well as more time in LLDAS (P < .0001) and were more likely to achieve sustained LLDAS (P < .001).
“LLDAS is a more stringent outcome measure than both BICLA and [SLE Responder Index-4 (SRI(4))], but is effectively concentric with these measures,” Morand and colleagues wrote. “LLDAS is associated with improved PtGA and HRQoL, suggesting additional value from measuring LLDAS attainment in SLE clinical trials and the potential to translate SLE clinical trial data into clinical practice to support treatment decisions.
Findings
“Our findings indicate that anifrolumab treatment results in significantly earlier and greater attainment of LLDAS and remission among patients who have moderate to severe SLE despite receiving standard of care,” they added. “These results suggest the potential utility of anifrolumab in a T2T paradigm for the management of SLE, which may lead to optimized therapy approaches and result in long-term benefits for patients with SLE.”