• Systemic lupus erythematosus (SLE)

Anifrolumab: 3-year data confirm long-term clinical benefit

New data from a long-term extension study show that anifrolumab was effective, safe, and tolerable in systemic lupus erythematosus (SLE) even in long-term use over three years [1]. Two post-hoc analyses of the TULIP trials also demonstrated that anifrolumab may contribute to an improvement in quality of life, among other benefits [2,3].

Anifrolumab (Saphnelo®) is the first targeted therapy approved for systemic lupus erythematosus (SLE). The fully human monoclonal antibody binds specifically to subunit 1 of the type I interferon receptor and blocks the activity of type I interferons [4]. The cytokines IFNα, IFNβ, and IFNκ are type I interferons associated with the regulation of inflammatory pathways involved in lupus [15–20]. The majority of adults with SLE have an elevated type I interferon gene signature, which is known to be associated with disease activity and severity [16,21].

Long-term safety and efficacy of Saphnelo® proven

In both pivotal studies, TULIP-1 and TULIP-2, anifrolumab resulted in improved disease control as well as sustained steroid sparing [5,6]. The objective of this randomized, double-blind, placebo-controlled, 216-week extension study was to evaluate the long-term safety and tolerability of anifrolumab 300 mg in patients with moderate to severe SLE [1]. This is the only placebo-controlled long-term extension (LTE) study in this disease to date. To enroll in the LTE, patients had to complete the 52-week treatment period in one of the two TULIP trials in which they received anifrolumab or placebo. The focus of the study was to compare patients treated continuously with anifrolumab 300 mg (n=257) or placebo (n=112) in the previous studies as well as in the LTE study.


Multisystemic disease SLE
Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of clinical manifestations that can affect many organs and cause a range of symptoms including pain, rashes, fatigue, joint swelling, and fever [7,8]. SLE belongs to the group of collagenoses. Currently, there are about 250,000 people with SLE in Europe. Most are women who received their diagnosis between the ages of 15 and 45 [9,10]. More than 50% of patients with SLE experience permanent organ damage caused by the disease or existing treatments. Consequences include worsening of symptoms and increased risk of mortality [11,12].


The results indicate a favorable long-term safety profile of anifrolumab with no new safety signals over three years [1]. Rates of serious adverse events (AEs), including events resulting in death, and AEs of special interest – including herpes zoster – were comparable between the two treatment groups. In addition, the LTE also demonstrated that the administration of anifrolumab was associated with lower glucocorticoid requirements and greater mean improvement in SLE Disease Activity Index 2000 (SLEDAI-2K) scores [1]. “We now have proof that the therapy based on type 1 IFN blockade is also safe and tolerable in the long term,” explained Prof. Peter Villiger, MD, full professor of rheumatology and clinical immunology, Monbijou Medical Center Bern [22]. “When we consider the additional data on sustained efficacy, we can conclude that patients may benefit from anifrolumab therapy over longer periods of time, particularly in terms of potential glucocorticoid savings,” he said.

Improving disease activity and patient-reported outcomes (PRO).

The effects of anifrolumab on the different organ domains and the subjectively patient-assessed effects in moderate to severe SLE were investigated in two recent post-hoc analyses of the phase III TULIP-1 and TULIP-2 trials [2,3]. Data from a total of 726 patients were pooled and analyzed. One of the post-hoc analyses confirmed the efficacy of anifrolumab across multiple organ domains. Thus, at week 52, a greater proportion of patients on anifrolumab showed improvement in SLE disease activity as measured by the SLEDAI-2K score in more commonly affected organ domains, including skin and joints. In addition, rapid improvement was also seen in less commonly affected organ domains, such as hematologic [2]. Another post-hoc analysis evaluated the effects of anifrolumab from the patient’s perspective using validated PRO** questionnaires [3]. The data indicate that anifrolumab leads to a decrease in fatigue and an increase in health-related quality of life (QoL): With anifrolumab, compared with placebo, more patients demonstrated an improvement in health-related quality of life ≥MCID$ at week 52 in all eight domains of the lupus-specific health-related QoL questionnaire [3].

** PRO=Patient Reported Outcomes
$ MCID=Minimal Clinically Important Difference

“SLE is usually accompanied by a significant loss of quality of life for patients. Due to the disease-related pain and fatigue, among other things, many find it difficult to participate in everyday work and social activities,” explained Prof. Johannes von Kempis, M.D., Specialist in Internal Medicine, Rheumatology and Immunology, Canton Hospital St. Gallen [22]. “Against this background, the currently available post-hoc data should be considered valuable. They indicate that anifrolumab may contribute to an improvement in PROs, including fatigue as well as health-related quality of life.”

Source: AstraZeneca

Literature:

  1. Kalunian KC, et al: A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Arthritis Rheumatol 2023; 75(2): 253-265.
  2. Morand EF, et al: Efficacy of anifrolumab across organ domains in patients with moderate-to-severe systemic lupus erythemato-sus: a post-hoc analysis of pooled data from the TULIP-1 and TULIP-2 trials. Lancet Rheumatol 2022;4: e282-292.
  3. Strand V, et al: Clinical meaningfulness of a British Isles Lupus Assessment Group-based composite lupus assessment response in terms of patient-reported outcomes in moderate to severe systemic lupus erythematosus: a post-hoc analysis of the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab. Lancet Rheumatol 2022;4:e198-207 and Supplementary Appendix.
  4. Drug Information, www.swissmedicinfo.ch,(last accessed 03/06/2023).
  5. Furie R, et al: Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019;1(4): e208-e219.
  6. Morand, E et al: Trial of anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med 2020; 382(3): 211-221.
  7. The Lupus Foundation of America. What is Lupus? www.lupus.org/resources/what-is-lupus,
    (last call 06.03.2023)
  8. American College of Rheumatology: guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis & Rheumatology 1999; 42: 1785-1796.
  9. Cornet A, et al: Living with systemic lupus erythematosus in 2020: a European patient survey. Lupus Sci Med 2021; 8:e000469.
  10. Lupus Europe: FAQs, www.lupus-europe.org/faqs,(last accessed 03/06/2023).
  11. Bruce IN, et al: Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the systemic lupus international collaborating Clinics (SLICC) inception cohort. Ann Rheum Dis. 2015; 74: 1706-1713.
  12. Segura BT, et al: Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort. Rheumatol 2020; 59 (3): 524-533.
  13. The Lupus Foundation of America. Lupus facts and statistics,
    www.lupus.org/resources/lupus-facts-and-statistics,(last accessed 03/06/2023)
  14. Mahieu MA, et al: A critical review of clinical trials in systemic lupus erythematosus. Lupus 2016; 25(10): 1122-1140.
  15. Rönnblom L, Leonard D: Interferon pathway in SLE: one key to unlocking the mystery of the disease Lupus Sci Med 2019; 6: e000270.
  16. Lauwerys, BR et al: Type I interferon blockade in systemic lupus erythematosus: where do we stand?. Rheumatol 2013; 53(8): 1369-1376.
  17. Sarkar MK, et al: Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. Ann Rheum Dis 2018; 77: 1653-1664.
  18. Jefferies CA: Regulating IRFs in IFN Driven Disease. Front Immunol 2019; 10: 325.
  19. López de Padilla CM, et al: The Type I Interferons: Basic Concepts and Clinical Relevance in Immune-mediated Inflammatory Diseases. Gene 2016; 576(101): 14-21.
  20. May L, et al: The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus. Arthritis Res Ther 2021; 23: 29.
  21. Crow MK: Type I Interferon in the Pathogenesis of Lupus. J Immunol. 2014; 192(12): 5459-5468.
  22. “Long-term safety and efficacy of anifrolumab confirmed over three years in lupus erythematosus (SLE),” 03/01/2023.

HAUSARZT PRAXIS 2023; 18(3): 44-45

Autoren
  • Mirjam Peter, M.Sc.
Publikation
  • HAUSARZT PRAXIS
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