Pooled data from the phase 3 TULIP program offer additional insight into the effects of anifrolumab use in people with moderate-to-severe systemic lupus erythematosus.
A pooled analysis of data from phase 3 studies examining anifrolumab (Saphnelo) in patients with moderate-to-severe systemic lupus erythematosus (SLE) is providing what may be the most comprehensive overview yet of the impact of the treatment a patient’s likelihood to achieve remission.
An analysis of the TULIP-1 and TULIP-2 trials, results of the study, which included more than 700 patients from the trials, indicate use of anifrolumab was associated with a more than 5-fold increase in likelihood of achieving sustained remission for 7 months or longer relative to their counterparts with SLE receiving placebo therapy.
A first-in-class type I interferon receptor antibody, anifrolumab received approval from the US Food and Drug Administration in August 2021 based on data from the aforementioned TULIP-1 and TULIP-2 trials as well as the phase 2 MUSE trial.2 The current study, which was presented at the Congress of Clinical Rheumatology (CCR) East 2023 annual meeting, was launched with an interest in exploring rate of SLE remission and factors associated with increased likelihood of sustained remission relative to placebo therapies from within the phase 3 TULIP program.
A randomized, double-blinded, 52-week placebo-controlled, multicenter trial, the TULIP-1 trial randomized 460 patients to 150mg anifrolumab, 300mg anifrolumab, or placebo every 4 weeks. The trial would go on to miss its primary endpoint of a reduction of disease activity, as measured by the SLE responder index.3
In TULIP-2, which was designed as a randomized, double-blind, placebo-controlled, parallel-group trial, a total of 362 patients underwent randomization. This trial met its primary endpoint, with results demonstrating a BICLA response in 47.8% of the anifrolumab group compared to 31.5% of the placebo arm. Additionally, analysis of secondary endpoints from the phase 3 program demonstrated consistent efficacy was observed for BICLA response, reduction in OCS use, and improvement in skin disease activity among those in TULIP-1 as was seen as TULIP-2.4
From the pair of phase 3 trials, investigators obtained information related to a cohort of 726 patients with moderate to severe SLE on standard of care, including 360 randomized to anifrolumab and 366 randomized to placebo therapy. According to investigators, all patients met the SLE 1997 criteria.1
For the purpose of analysis, Definition of Remission In SLE (DORIS) response served as the primary outcome of interest. DORIS response was defined as clinical SLE Disease Activity Index 2000 score of 0, a Physician’s Global Assessment less than 0.5, prednisone or equivalent dose of 5 mg or less per day, no use of restricted medications, and no premature discontinuation of study drug. Investigators pointed out plans to assess remission rate by timepoint, time to first remission, cumulative/percentage of time and proportion of consecutive visits in remission using the Cochran–Mantel–Haenszel (CMH) approach, logistic regression, Cox regression, and analysis of covariance.1
Upon analysis, results indicated remission rates generally increased over time, with 35 of 360 anifrolumab-treated patients achieving remission between weeks 36 and 52 compared to just 3% with placebo therapy. When examining timing of remission, results indicated remission was achieved earlier in patients treated with 300 mg anifrolumab than with placebo therapy (Hazard ratio [HR], 2.4 [95% CI, 1.5-3.8]; P <.001). Further analysis indicated differences in remission rates using the CMH approach were greater in the 300 mg anifrolumab group relative to placebo at all timepoints from week 28 to week 52 (all P <.05).1
Additional results highlighted by investigators included improvements in cumulative time and percentage of time spent in remission as well as cumulative time in remission thresholds of 20% or greater (Odds ratio [OR, 2.7 [95% CI, 1.5-5.1]; P=.002) and 50% or greater (OR, 3.5 [95% CI, 1.1-11.0]; P=.029). When assessing sustained remission, results indicated anifrolumab treated patients were more likely to achieve remission for 3 or more consecutive monthly visits (OR, 2.5 [95% CI, 1.4-4.4]; P=.003), 5 or more consecutive monthly visits (OR, 3.1 [95% CI, 1.3-7.0]; P=.003), and 7 or more consecutive monthly visits (OR, 5.6 [95% CI, 1.6-19.7]; P=.007).1
“Nearly 10% of anifrolumab-treated patients achieved remission, suggesting that DORIS response is an attainable outcome for patients with SLE treated with anifrolumab, and was associated with earlier, more frequent, more prolonged, and more sustained achievement of remission compared with placebo,” wrote investigators.1