Treatment with anifrolumab vs placebo is associated with earlier, more frequent, and more prolonged and sustained achievement of Lupus Low Disease Activity State (LLDAS) and remission among patients with moderate to severe systemic lupus erythematosus (SLE), according to study results published in Annals of the Rheumatic Diseases.
Researchers conducted a post hoc analysis using pooled data from 2 phase 3 trials (Treatment of Uncontrolled Lupus via the Interferon Pathway [TULIP-1; ClinicalTrials.gov Identifier: NCT02446912 and TULIP-2; ClinicalTrials.gov Identifier: NCT02446899]). They evaluated the attainment of LLDAS among patients with SLE who received treatment with anifrolumab.
In the study, LLDAS was defined as a SLE Disease Activity Index 2000 (SLEDAI-2K) score of 4 or less without major organ activity; no new disease activity; Physician’s Global Assessment (PGA) score of 1 or less; prednisone of 7.5 mg/day or lesser; and no nonstandard immunosuppressive medication dosing.
A total of 819 patients with moderate to severe SLE were enrolled in the TULIP-1 and
-2 trials. Patients were randomly assigned to receive anifrolumab 300 mg (n=360), anifrolumab 150 mg (n=93), or placebo (n=366).
Researchers conducted an analysis agnostic to treatment in the entire study cohort, including patients in the TULIP-1 trial who received treatment with anifrolumab 150 mg every month, to evaluate the association of LLDAS attainment with other measures of treatment response.
At 52 weeks, 25.0% (n=205/819) of the participants attained LLDAS. The individual components of LLDAS were achieved with variable frequency at week 52, with a
SLEDAI-2K score of 4 or less attained least often (n=415/726; 57.2%).
Among the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA)-responders at 52 weeks, 58.5% (n=186/318) achieved LLDAS compared with 3.8% (n=19/501) of the BICLA-nonresponders (95% CI, 49.0-60.3; P <.0001). Overall, 90.7% of LLDAS-responders at week 52 were BICLA-responders as well.
In addition, among SLE Responder Index-4 (SRI)-responders at 52 weeks, 53.4% (n=203/380) achieved LLDAS compared with 0.005% (n=2/439) of SRI(4)-nonresponders (95% CI, 48.4-58.6; P <.0001). Improvements from baseline in PGA scores at 52 weeks were 3-fold higher among those who attained LLDAS.
At 52 weeks, 30.0% (n=108/360) of patients who received anifrolumab and 19.6% (n=72/366) of those who received placebo attained LLDAS (odds ratio [OR], 1.8; 95% CI, 1.3-2.5; P =.0011).
Anifrolumab vs placebo was associated with earlier attainment of LLDAS (time to first LLDAS: hazard ratio [HR], 1.76; 95% CI, 1.35-2.30; P <.0001), increased cumulative time in LLDAS (P <.0001), and a higher likelihood of sustained LLDAS (P <.001).
A total of 15.3% (n=55/360) of patients who received anifrolumab vs 7.6% (n=28/366) of those who received placebo achieved remission by week 52 (OR, 2.2; 95% CI, 1.4-3.6; P =.0013).
One of the study limitations was that the TULIP trials included patients with moderate to severe SLE that mainly affected mucocutaneous and musculoskeletal domains, thus those with severe active renal or central nervous system disease were excluded from the analysis.
The study authors concluded, “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.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Morand EF, Abreu G, Furie RA, Golder V, Tummala R. Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus. Ann Rheum Dis. Published online January 23, 2023. doi:10.1136/ard-2022-222748