Scoping literature review to identify candidate domains for the OMERACT Systemic Lupus Erythematosus core outcome set.Seminars in arthritis and rheumatism • November 07, 2024
Wils Nielsen, Fadi Kharouf, Carolina Grajales, Aarabi Thayaparan, Melanie Anderson, Vibeke Strand, Lee Simon, Dennisse Bonilla, Eric Morand, Julian Thumboo, Martin Aringer, Marta Mosca, Ian Bruce, Elektra Papadopoulos, Karina Torralba, Laura Whitall Garcia, Cheryl Rosen, Ioannis Parodis, Alfred Kim, Maya Desai, Yvonne Enman, Beverley Shea, Daniel Wallace, Yashaar Chaichian, Sandra Navarra, Cynthia Aranow, Meggan Mackay, Kimberly Trotter, Oshrat Tayer Shifman, AlĂ Duarte GarcĂa, Lai Shan Tam, Manuel Ugarte Gil, Guillermo Pons Estel, John Reynolds, Mandana Nikpour, Alberta Hoi, Juanita Romero Diaz, Amita Aggarwal, DanaĂ« Papachristos, Chi Mok, Keishi Fujio, Rosalind Ramsey Goldman, Alexandra Legge, Laurent Arnaud, Irene E Bultink, Stephanie Finzel, Reinhard Voll, Guillermo Ruiz Irastorza, LuĂs InĂŞs, Simone Appenzeller, Chrisanna Dobrowolski, Ann Clarke, Diane Kamen, Michelle Barraclough, Chiara Tani, Jose GĂłmez Puerta, Victoria Werth, Patti Katz, Anca Askanase, Kathleen Bingham, Dafna Gladman, Sindhu Johnson, Aaron Drucker, Behdin Nowrouzi Kia, Zahi Touma
Objective: To identify candidate Systemic Lupus Erythematosus (SLE) domains from the literature for consideration towards the development of the SLE Core Outcome Set.
Methods: This was a comprehensive scoping literature review of SLE clinical trials and systematic reviews published since 2010. Studies were identified from 5 databases and were screened for eligibility. Candidate domains were extracted from the included studies. Candidate domains were winnowed and binned by the Outcome Measures in Rheumatology (OMERACT) SLE Advisory Group.
Results: Of the 4063 studies identified, 507 met inclusion criteria and proceeded to data extraction. Multiple domains and items were extracted, which winnowing and binning reduced to 25 candidate domains.
Conclusions: The 25 candidate domains cover the important aspects of SLE and the 4 core areas of disease impact according to OMERACT framework. The 25 candidate domains constitute a feasible and manageable number of domains to proceed with to the core domain consensus stage that covers the wide range of impact of SLE. The candidate domains will be supplemented by ongoing qualitative research with patients living with SLE to identify additional domains before proceeding to the consensus stage.
Progress in the use of type I interferon blockade in systemic lupus erythematosus.Expert Opinion On Biological Therapy • July 22, 2025
Iolanda Miceli, Eric Morand, Sarah Jones
The successful clinical trials of the type I interferon (IFN) receptor monoclonal antibody, anifrolumab, have proven the benefit of IFN blockade in systemic lupus erythematosus (SLE), and paved the way for novel therapies targeting this pathway. This review will cover the updated evidence regarding the efficacy and safety of anifrolumab since its positive phase III trial in 2020. In addition, indications of the clinical benefit of emerging IFN-targeting therapies, such as monoclonal antibodies targeting IFN-producing cells and small molecule inhibitors of IFN signaling, currently in phase II/III clinical trials will be discussed. Evidence from clinical trials and real-world studies have revealed the potential for IFN blockade to reduce disease activity and flares, improve glucocorticoid (GC) tapering and increase the attainment of treat-to-target goals in SLE, including in refractory patients. The efficacy of IFN blockade across different SLE disease manifestations and patient subgroups remains under investigation, as well as the ability of such treatments to reduce end organ damage. Regardless, it is clear that IFN blockade has earned a place as part of the standard of care in SLE. Future studies are needed to define whether IFN blockade moves toward being a first line treatment.
Prevalence and outcomes of a pilot definition of severe refractory systemic lupus erythematosus: observations from a multinational Asia-Pacific cohort.Arthritis Research & Therapy • May 17, 2025
Rangi Kandane Rathnayake, Worawit Louthrenoo, C Lau, Laniyati Hamijoyo, Jiacai Cho, Aisha Lateef, Shue Luo, Yeong-jian Wu, Sandra Navarra, Leonid Zamora, Zhanguo Li, Yi-hsing Chen, Shereen Oon, Madelynn Chan, Sargunan Sockalingam, Yanjie Hao, Zhuoli Zhang, Sang-cheol Bae, Jun Kikuchi, Tsutomu Takeuchi, Yasuhiro Katsumata, Bmdb Basnayake, Fiona Goldblatt, Sean O'neill, Kristine Pek Ling Ng, Nicola Tugnet, Mark Sapsford, Yih Poh, Cherica Tee, Michael Tee, Naoaki Ohkubo, Adrienne Lefeber, Tamas Shisha, Yoshiya Tanaka, Vera Golder, Mandana Nikpour, Alberta Hoi, Peter Gergely, Eric Morand
Background: Emerging therapies have the potential to be used in patients with severe refractory systemic lupus erythematosus (srSLE), but no agreed definition of srSLE exists. We evaluated a pilot srSLE definition to assess whether a set of disease activity and treatment thresholds could identify patients with poor outcomes.
Methods: Data from a 13-country longitudinal SLE cohort, collected prospectively between 2013 and 2020 were analysed. srSLE was defined if a patient was in high disease activity (SLEDAI-2K ≥ 10) despite combination use of at least glucocorticoids (GC) and immunosuppressants (IS) at both the index and preceding visit. Synchronised to the index srSLE visit, we assessed disease activity, medication use and treat-to-target (T2T) endpoint attainment over 12 months (m).
Results: Of 3,744 patients studied, 578 (14%) had srSLE, in 1,810 visits. The median [IQR] SLEDAI-2K at the srSLE index visit was 12 [10, 14], which decreased to 6 [4, 10] at 6m and 12m. Most patients remained on combination anti-malarial, GC, and IS at all follow-up time points. The median [IQR] GC dose at the index visit was 10 [5, 20] mg/day; this reduced to 8 mg [5.0, 12.9] at 6m and 5 mg [5.0, 10.0] at 12m. Less than a quarter of patients attained LLDAS and only 1% attained GC-free remission over 12 months.
Conclusions: A draft definition of srSLE was clearly associated with poor outcomes. Work to evaluate multiple thresholds with which to define srSLE, and their outcomes, is warranted.
Informing trial measurement in systemic lupus erythematosus: frequency of domain-specific disease activity in a multinational cohort.Lupus Science & Medicine • March 06, 2025
Raychel Barallon, Kathryn Connelly, Vera Golder, Worawit Louthrenoo, Yi-hsing Chen, Jiacai Cho, Aisha Lateef, Laniyati Hamijoyo, Shue-fen Luo, Yeong-jian Wu, Sandra Navarra, Leonid Zamora, Zhanguo Li, Sargunan Sockalingam, Yasuhiro Katsumata, Masayoshi Harigai, Yanjie Hao, Zhuoli Zhang, Madelynn Chan, Jun Kikuchi, Tsutomu Takeuchi, Shereen Oon, Sang-cheol Bae, Fiona Goldblatt, Sean O'neill, Kristine Ng, Annie Law, Bmdb Basnayake, Nicola Tugnet, Sunil Kumar, Cherica Tee, Michael Tee, Yoshiya Tanaka, Chak Lau, Mandana Nikpour, Alberta Hoi, Eric Morand, Rangi Kandane Rathnayake
Objective: To report the prevalence of disease activity in individual SLE organ domains, including prevalence stratified by the most common disease activity cut-off score for clinical trial eligibility (SLE Disease Activity Index 2000; SLEDAI-2K ≥6).
Methods: We used data from a multinational longitudinal SLE cohort, prospectively collected between 2013 and 2020. Disease activity was categorised by the SLEDAI-2K into nine organ systems. We calculated proportions of organ-specific disease activity in the overall cohort and stratified by SLEDAI-2K ≥6 or <6, on both a per-patient and per-visit level.
Results: We included 4102 patients (92.0% female, 88.9% Asian) contributing 42 345 eligible visits. Serological disease activity was most prevalent, affecting 75.5% of patients at least once during follow-up, followed by renal (41.6%), cutaneous (36.5%), musculoskeletal (20.1%) and haematological (19.1%) activity. Serositis (3.4%), vasculitis (3.4%), central nervous system activity (3.0%) and fever (2.9%) occurred infrequently. In patient visits with an SLEDAI-2K ≥6 (n=10 031), the most common active manifestations were serological (89.8%), renal (72.9%), cutaneous (26.4%) and musculoskeletal (14.3%). In patient visits with an SLEDAI-2K <6 (n=32 314), renal (7.3%), cutaneous (6.7%), haematological (5.8%) and musculoskeletal (1.3%) disease activity were still present.
Conclusions: Serological, renal, cutaneous, musculoskeletal and haematological manifestations predominate in patients with active SLE; other organs are affected infrequently. Trial outcome measures could focus on measuring change in these systems and omit detailed analysis of rare events. Conversely, some patients with active disease in common domains would be ineligible for clinical trials based on an SLEDAI-2K <6. Use of organ-specific activity measures and inclusion criteria may overcome this limitation.
10 years in lupus - progress, but not enough.Trends In Molecular Medicine • January 28, 2025
Eric Morand, Sarah Jones
Systemic lupus erythematosus (SLE, lupus) remains an enigmatic diagnosis with a poor prognosis. SLE is characterised by complex biology and heterogeneous clinical manifestations that create a major hurdle to the approval of new medicines and contribute to multiple trial failures. While the pace of research has accelerated, drugs currently in development target a limited spectrum of mechanisms, tempering hope that any will be a panacea. The pace of translation lags behind advances in basic science, and this continues to cost patients dearly. The unacceptable metabolic adverse effects of glucocorticoids have rightly driven treatment guidelines towards ever more stringent dose-reduction targets, and new research is ongoing to develop a safe and reliable glucocorticoid replacement that will be active across a breadth of inflammatory pathways.
