Background/Purpose: Fatigue is highly prevalent and severely affects health-related quality of life (HRQoL) in patients with SLE.^1,2  We previously demonstrated that, compared with placebo, a numerically greater proportion of patients with moderate to severe SLE receiving treatment with the type I IFN receptor antibody anifrolumab in the phase 3 TULIP-1 and TULIP-2 trials reported improvements in fatigue at Week 52.³ However, fatigue fluctuates over time,² and treatments that enable sustained improvements are needed. In this post hoc analysis of the TULIP-1/-2 trials, we assessed sustained fatigue response in patients receiving anifrolumab versus placebo.      

Methods: Adults with moderate to severe SLE despite standard therapy were randomized in the double-blind, 52-week TULIP-1/-2 trials (NCT02446912, NCT02446899) to receive intravenous anifrolumab 300 mg or placebo every 4 weeks (Q4W).³ Patients completed the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F) questionnaire Q4W to provide a measurement of their fatigue and its impact on daily life. Based on the minimum clinically important difference, FACIT–F response was defined as a ≥4-point improvement from Week 0 assessment.³ Sustained FACIT–F response was defined as being achieved from the time of first FACIT–F response after which all subsequent assessments met the definition of response. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using a Cox regression model with treatment and stratification factors of SLEDAI-2K score at screening, Week 0 prednisone or equivalent dosage, and type 1 IFN test result at screening as covariates. Patients who received restricted medications beyond protocol-allowed thresholds, discontinued investigational product, or could not be evaluated for FACIT–F were considered nonresponders. P-values are nominal.

Results: Similar proportions of patients achieved a FACIT–F response at any time during the trials with anifrolumab and placebo (71.8% [257/358] and 71.1% [256/360]; HR 0.99, 95% CI 0.83–1.18). A numerically higher percentage of patients achieved a FACIT–F response at Week 52 with anifrolumab versus placebo (34.1% [122/358] vs 26.1% [94/360]). Patients on anifrolumab achieved sustained response earlier in the trials versus placebo (HR 1.30, 95% CI 1.00–1.71, nominal P=0.0542), with the numerical difference between the groups favoring anifrolumab versus placebo maintained from Week 4 to Week 52 (Figure).

Conclusion: Considering the severe impact of fatigue on HRQoL in patients with SLE¹, it is important that improvements in fatigue be not only temporarily achieved but sustained. Though the proportions of patients achieving FACIT-F response during the trials did not differ with treatment, a numerically higher proportion of patients treated with anifrolumab achieved a FACIT–F response early in the trials that was sustained over time compared with placebo. Our findings are suggestive that anifrolumab treatment may provide longer-term improvements in fatigue and that further research is warranted.

References:

1. Elefante E. RMD Open. 2020;6(1):e001133.

2. Kawka L. J Clin Med. 2021;10(17):3996.

3. Strand V. Lancet Rheumatol. 2022;4(3):e198–207.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sustained-functional-assessment-of-chronic-illness-therapy-fatigue-response-in-patients-with-sle-receiving-anifrolumab-alongside-standard-therapy/