Highlights
- Anifrolumab demonstrated sustained, numerically greater improvements in patient-reported outcomes (PROs) compared to placebo over 4 years in moderate-to-severe systemic lupus erythematosus (SLE).
- Key domains showing benefit included bodily pain and mental health, as measured by SF-36v2, as well as health utility indices (SF-6D, EQ-5D-5L).
- These benefits occurred in the context of improved disease activity, reduced glucocorticoid requirements, and a tolerable safety profile.
- The TULIP-LTE study supports the long-term use of anifrolumab as an effective option to enhance health-related quality of life in SLE.
Study Background and Disease Burden
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease marked by unpredictable flares, organ involvement, and a substantial impact on quality of life. Despite advances in therapy, many patients experience persistent symptoms, high glucocorticoid exposure, and decreased physical and mental well-being. Traditional disease activity measures often fail to capture the full patient experience, making patient-reported outcomes (PROs) essential for holistic disease assessment. There is a recognized unmet need for therapies that not only control disease activity but also improve the lived experience of SLE.
Anifrolumab, a monoclonal antibody targeting the type I interferon receptor, has shown clinical efficacy in reducing disease activity in phase 3 TULIP-1 and TULIP-2 trials. However, the durability of PRO improvements with long-term therapy remained unknown prior to the TULIP-LTE extension study.
Study Design
TULIP-LTE was a 3-year, randomized, double-blind, placebo-controlled, phase 3 long-term extension of the TULIP-1 and TULIP-2 trials. Eligible patients with moderate-to-severe SLE, who completed the initial 52-week trials while receiving standard care, were reconsented and continued their original treatment assignment—anifrolumab 300 mg IV every 4 weeks or placebo—for an additional 3 years, totaling up to 4 years of continuous treatment.
A total of 369 patients entered the extension (257 anifrolumab, 112 placebo). The cohort was predominantly female (92%), with a mean age of 42.8 years. PROs were rigorously assessed using validated instruments:
- Short Form-36 version 2 acute recall (SF-36v2 [acute])
- Patient Global Assessment of disease activity
- EuroQoL 5 Dimensions-5 Levels (EQ-5D-5L)
- Work Productivity and Activity Impairment-Lupus (WPAI-Lupus)
- Health utility indices (SF-6D and EQ-5D-5L derived)
All analyses were performed in the modified intention-to-treat (mITT) population, adjusting for repeated measures over time.
Key Findings
Over the 4-year treatment period, both the anifrolumab and placebo groups reported improvements from baseline in most PROs, but the magnitude of improvement was consistently higher in the anifrolumab group.
SF-36v2 (Acute) Domains:
At week 208 (4 years), improvements from baseline were numerically greater for anifrolumab in bodily pain (least-squares mean difference 5.9 [95% CI -0.7 to 12.5]) and mental health (3.7 [-1.2 to 8.6]) compared to placebo. These domains are especially relevant in SLE, where pain and psychological distress are major contributors to disease burden. Although the confidence intervals crossed zero, the sustained numerical trend across multiple timepoints and domains is notable.
Health Utility Indices:
Improvements in SF-6D—a summary measure of health utility—were generally greater with anifrolumab, evident as early as week 24 (least-squares mean difference 0.013 [-0.007 to 0.032]) and maintained at week 208 (0.016 [-0.010 to 0.042]). This finding persisted across EQ-5D-5L assessments.
Other PROs:
Patient Global Assessment, EQ-5D-5L, and WPAI-Lupus scores also improved more in the anifrolumab group, though most differences were numerically, rather than statistically, significant.
Clinical and Safety Context:
The PRO improvements were observed alongside reduced disease activity, lower glucocorticoid doses, and a tolerable safety profile in the anifrolumab group. No new safety signals emerged during the long-term extension, supporting the durability and acceptability of this therapy.
Expert Commentary
The TULIP-LTE study represents one of the longest controlled evaluations of PROs in SLE, addressing a critical gap in evidence. The sustained, multidimensional improvements in quality of life, especially in pain and mental health, are clinically meaningful for patients who often experience these symptoms despite immunosuppressive therapy.
It is important to note that while many between-group differences did not reach statistical significance, the consistent numerical advantage and long-term trajectory favoring anifrolumab provide reassurance of its potential to address unmet patient needs. Limitations include possible selection bias (patients who tolerated and responded to therapy in the initial trials were more likely to enter the extension) and the exploratory nature of most endpoints.
Guidelines from organizations such as EULAR and ACR increasingly emphasize the importance of PROs and steroid-sparing in lupus management—this study supports the integration of anifrolumab into such strategies, especially for patients with refractory symptoms impacting quality of life.
Conclusion
Anifrolumab, as demonstrated in the TULIP-LTE trial, offers sustained improvement in patient-reported outcomes and health-related quality of life for SLE patients receiving standard therapy. These benefits are achieved in the context of disease activity reduction, glucocorticoid sparing, and a favorable safety profile. Future research should focus on identifying patient subgroups most likely to benefit, optimizing PRO measurement, and further clarifying the long-term risk-benefit profile.
References
1. Strand V, Kalunian KC, Lee KW, Seo C, Abreu G, Tummala R, Al-Mossawi H, Duncan EA, Lindholm C. Long-term effect of anifrolumab on patient-reported outcomes in systemic lupus erythematosus (TULIP-LTE): a randomised, placebo-controlled, phase 3 long-term extension trial. Lancet Rheumatol. 2025 Jul;7(7):e485-e494. doi: 10.1016/S2665-9913(25)00022-0.
2. Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an Anti–Interferon α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. N Engl J Med 2019;382:211-221.
3. van Vollenhoven RF et al. EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78:736-745.
