Validation of the Lupus Low Disease Activity State (LLDAS) in the Asia Pacific Region

NCT03138941 | Recruiting DMC

• 1 other identifier: APLC LLDAS Study
• Study Type: observational
• Target: 5,000
• Locations: 11 countries
• Sites: 20

Brief Summary

Lupus Low Disease Activity State (LLDAS) study is an international, multi-centre prospective study, developed by the Asia Pacific Lupus Collaboration (APLC) to investigate whether the attainment of LLDAS is associated with improved outcomes in patients with Systemic Lupus Erythematosus (SLE). SLE, or lupus, is the archetypal multisystem autoimmune disease, with an estimated incidence of 5-50 cases per 100,000 people. Patients with SLE, usually young women, suffer a marked loss of life expectancy, and severe morbidity, due to a heterogeneous range of clinical manifestations caused by autoimmune-mediated inflammation of multiple organs. The most severe manifestations of SLE are the accrual of irreversible organ damage, especially renal and central nervous system (CNS) involvement. As there is no effective targeted monotherapy for SLE, patients also suffer severe toxicity from the use of glucocorticoids and broad-spectrum immunosuppressive therapies. Despite combination therapy with current drugs, many studies show that the majority of patients suffer inadequate disease control and inexorably accrue permanent organ damage over time. The diversity of clinical features of active SLE has made quantification of disease activity problematic. Although there are a number of published systems in use to measure SLE disease activity, there are widely acknowledged problems with these instruments. Published definitions of remission are so stringent that they are met by less than 5% of patients. This lead to the realisation that rather than lupus remission, a lupus low disease activity state target may be more feasible, and that patients with low disease activity are more homogeneous than patients with active disease. Thus, the development of a definition of lupus low disease activity, which is feasible and has face validity, escapes the complexity of attempts to quantify heterogeneous states of active disease. In this study, the investigators will prospectively collect longitudinal data on consecutive SLE patients at each centre to evaluate the LLDAS definition. Protection from organ damage accrual as the primary endpoint.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• SLICC-ACR Damage Index

  Organ damage accrual

  Approximately 5-10 years

Secondary Outcomes (2)

• SFv2-36

  Approximately 5-10 years

• Mortality

  Approximately 5-10 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult SLE patients with confirmed lupus

You may qualify if:

• All patients have to meet either the 1997 American College of Rheumatology (ACR) Modified Classification Criteria for SLE, with at least four of the 11 items; or alternatively, fulfil the Systemic Lupus International Collaborating Clinics (SLICC) 2012 Classification Criteria, with at least four of the 17 items (at least one clinical and one immunological criterion) or with lupus nephritis in the presence of at least one immunological criteria. Patients can be either newly diagnosed or longstanding lupus patients.
• All patients must be over the age of 18 and competent to provide written consent.

You may not qualify if:

• Patients less than 18 years of age and patients who are unable to consent are excluded from the study.

Sponsors & Collaborators

• Monash University: lead
• Flinders Medical Centre, Adelaide, AUSTRALIA: collaborator
• St. Vincent's Hospital, Melbourne, AUSTRALIA: collaborator
• Royal Adelaide Hospital, Adelaide, AUSTRALIA: collaborator
• University of New South Wales, Sydney, AUSTRALIA: collaborator
• People's Hospital, Peking University Health Science Center, Beijing, CHINA: collaborator
• Peking University First Hospital, Beijing, CHINA: collaborator
• The University of Hong Kong: collaborator
• University of Padjadjaran, Bandung, INDONESIA: collaborator
• Tokyo Women's Medical University, JAPAN: collaborator
• University of Occupational and Environmental Health, JAPAN: collaborator
• Keio University, JAPAN: collaborator
• Hanyang University Hospital for Rheumatic Diseases, REPUBLIC OF KOREA: collaborator
• University of Santo Tomas Hospital, Philippines: collaborator
• National University Hospital, Singapore: collaborator
• Tan Tock Seng Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator
• Taichung Veterans General Hospital: collaborator
• Chiang Mai University Hospital, THAILAND: collaborator
• Middlemore Hospital, New Zealand: collaborator
• North Shore Hospital, Auckland, NEW ZEALAND: collaborator
• Auckland District Health Board, Auckland, NEW ZEALAND: collaborator
• Teaching Hospital Kandy, SRI LANKA: collaborator
• University of the Philippines, Philippines: collaborator

Study Sites (20)

Rheumatology Unit, Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Department of Rheumatology, Flinders Medical Centre

Adelaide, South Australia, 5042, Australia

RECRUITING

School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing & Health Sciences

Clayton, Victoria, 3168, Australia

RECRUITING

Department of Rheumatology, St Vincent's Hospital (Melbourne)

Fitzroy, Victoria, 3065, Australia

RECRUITING

Department of Rheumatology and Immunology, People's Hospital Peking University Health Science Center

Beijing, Western District, 100044, China

RECRUITING

Rheumatology and Immunology department, Peking University First Hospital

Beijing, Xicheng District, 100034, China

RECRUITING

Division of Rheumatology & Clinical Immunology, Department of Medicine, Queen Mary Hospital, the University of Hong Kong

Pok Fu Lam, Hong Kong

ACTIVE NOT RECRUITING

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Padjadjaran University/ Hasan Sadikin General Hospital

Bandung, West Java, Indonesia

RECRUITING

The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health

Kitakyushu, 807-8555, Japan

RECRUITING

Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University

Tokyo, 160-8582, Japan

RECRUITING

Institute of Rheumatology, Tokyo Women's Medical University

Tokyo, 162-0054, Japan

RECRUITING

Joint and Bone Center, University of Santo Tomas Hospital

Manila, 1008, Philippines

RECRUITING

University of the Philippines

Quezon City, Philippines

RECRUITING

Rheumatology Division, University Medical Cluster, National University Hospital

Singapore, 119074, Singapore

RECRUITING

Department of Rheumatology, Allergy & Immunology, Tan Tock Seng Hospital

Tan Tock Seng, 308433, Singapore

RECRUITING

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases

Seoul, 04763, South Korea

RECRUITING

Division of Nephrology, Teaching Hospital Kandy, Sri Lanka

Kandy, Sri Lanka

RECRUITING

Department of Rheumatology, Allergy and Immunology Chang Gung Memorial Hospital Chang Gung University

Guishan, Taoyuan County, 333, Taiwan

RECRUITING

Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital

Taichung, 40705, Taiwan

RECRUITING

Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University Hospital

Chiang Mai, Muang District, 50200, Thailand

RECRUITING

Related Publications (12)

• Golder V, Huq M, Franklyn K, Calderone A, Lateef A, Lau CS, Lee ALH, Navarra STV, Godfrey T, Oon S, Hoi AYB, Morand EF, Nikpour M. Does expert opinion match the operational definition of the Lupus Low Disease Activity State (LLDAS)? A case-based construct validity study. Semin Arthritis Rheum. 2017 Jun;46(6):798-803. doi: 10.1016/j.semarthrit.2017.01.007. Epub 2017 Jan 18.

  PMID: 28216192 BACKGROUND

• Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, Li ZG, Luo SF, Sockalingam S, Lau CS, Mok MY, Lateef A, Franklyn K, Morton S, Navarra ST, Zamora L, Wu YJ, Hamijoyo L, Chan M, O'Neill S, Goldblatt F, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study. Arthritis Res Ther. 2017 Mar 20;19(1):62. doi: 10.1186/s13075-017-1256-6.

  PMID: 28320433 BACKGROUND

• Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, Li ZG, Luo SF, Sockalingam S, Lau CS, Lee AL, Mok MY, Lateef A, Franklyn K, Morton S, Navarra ST, Zamora L, Wu YJ, Hamijoyo L, Chan M, O'Neill S, Goldblatt F, Morand EF, Nikpour M; Asia-Pacific Lupus Collaboration. Frequency and predictors of the lupus low disease activity state in a multi-national and multi-ethnic cohort. Arthritis Res Ther. 2016 Nov 9;18(1):260. doi: 10.1186/s13075-016-1163-2.

  PMID: 27829463 BACKGROUND

• Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, Wahono CS, Chen SL, Jin O, Morton S, Hoi A, Huq M, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615-21. doi: 10.1136/annrheumdis-2015-207726. Epub 2015 Oct 12.

  PMID: 26458737 BACKGROUND

• Kandane-Rathnayake R, Golder V, Louthrenoo W, Luo SF, Jan Wu YJ, Li Z, An Y, Lateef A, Sockalingam S, Navarra SV, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Hao Y, Zhang Z, Al-Saleh J, Khamashta M, Takeuchi T, Tanaka Y, Bae SC, Lau CS, Hoi A, Nikpour M, Morand EF. Development of the Asia Pacific Lupus Collaboration cohort. Int J Rheum Dis. 2019 Mar;22(3):425-433. doi: 10.1111/1756-185X.13431. Epub 2018 Nov 5.

  PMID: 30398013 BACKGROUND

• Golder V, Kandane-Rathnayake R, Huq M, Nim HT, Louthrenoo W, Luo SF, Wu YJ, Lateef A, Sockalingam S, Navarra SV, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Lau CS, Li ZG, Hoi A, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. Lancet Rheumatol. 2019 Oct;1(2):e95-e102. doi: 10.1016/S2665-9913(19)30037-2. Epub 2019 Sep 6.

  PMID: 38229349 BACKGROUND

• Golder V, Kandane-Rathnayake R, Huq M, Louthrenoo W, Luo SF, Wu YJ, Lateef A, Sockalingam S, Navarra SV, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Lau CS, Li ZG, Hoi A, Nikpour M, Morand EF; Asia Pacific Lupus Collaboration. Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study. Lancet Rheumatol. 2019 Oct;1(2):e103-e110. doi: 10.1016/S2665-9913(19)30048-7. Epub 2019 Sep 25.

  PMID: 38229337 BACKGROUND

• Kandane-Rathnayake R, Zolio L, Choi J, Golder V, Louthrenoo W, Chen YH, Cho J, Lateef A, Hamijoyo L, Luo SF, Wu YJ, Navarra SV, Zamora L, Li Z, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Chan M, Kikuchi J, Takeuchi T, Oon S, Bae SC, Goldblatt F, O'Neill S, Ng KPL, Law A, Basnayake B, Tugnet N, Kumar S, Tee C, Tee M, Tanaka Y, Lau CS, Hoi A, Nikpour M, Morand EF. Predictors of damage accrual by organ domain in systemic lupus erythematosus. Rheumatology (Oxford). 2025 Nov 18:keaf610. doi: 10.1093/rheumatology/keaf610. Online ahead of print.

  PMID: 41252474 DERIVED

• Kandane-Rathnayake R, Hoi A, Louthrenoo W, Golder V, Chen YH, Cho J, Lateef A, Hamijoyo L, Luo SF, Wu YJ, Navarra S, Zamora L, Li Z, Yao H, Sockalingam S, Katsumata Y, Hao Y, Zhang Z, Basnayake BMDB, Chan M, Kikuchi J, Kaneko Y, Takeuchi T, Oon S, Bae SC, O'Neill S, Hassett G, Goldblatt F, Ng KPL, Poh YJ, Tugnet N, Sapsford M, Chan S, Tee C, Tee ML, Ohkubo N, Tanaka Y, Lau CS, Nikpour M, Morand E. Impact of glucocorticoid dose threshold in definition of lupus low disease activity state: a multinational observational cohort study. Lupus Sci Med. 2025 Nov 11;12(2):e001714. doi: 10.1136/lupus-2025-001714.

  PMID: 41219118 DERIVED

• Golder V, Kandane-Rathnayake R, Li N, Louthrenoo W, Chen YH, Cho J, Lateef A, Hamijoyo L, Luo SF, Wu YJ, Navarra SV, Zamora L, Li Z, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Basnayake D, Chan M, Kikuchi J, Takeuchi T, Bae SC, Goldblatt F, Oon S, O'Neill S, Ng K, Law A, Tugnet N, Kumar S, Tee C, Tee M, Ohkubo N, Tanaka Y, Lau CS, Hoi A, Nikpour M, Morand EF; Asia Pacific Lupus Collaboration. Association of sustained lupus low disease activity state with improved outcomes in systemic lupus erythematosus: a multinational prospective cohort study. Lancet Rheumatol. 2024 Aug;6(8):e528-e536. doi: 10.1016/S2665-9913(24)00121-8. Epub 2024 Jun 11.

  PMID: 38876129 DERIVED

• Golder V, Kandane-Rathnayake R, Louthrenoo W, Chen YH, Cho J, Lateef A, Hamijoyo L, Luo SF, Wu YJ, Navarra SV, Zamora L, Li Z, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Basnayake BMDB, Chan M, Kikuchi J, Takeuchi T, Bae SC, Oon S, O'Neill S, Goldblatt F, Ng KPL, Law A, Tugnet N, Kumar S, Tee C, Tee M, Ohkubo N, Tanaka Y, Lau CS, Nikpour M, Hoi A, Morand EF; Asia Pacific Lupus Collaboration. Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State in Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus. J Rheumatol. 2024 Aug 1;51(8):790-797. doi: 10.3899/jrheum.2023-0900.

  PMID: 38490668 DERIVED

• Kandane-Rathnayake R, Golder V, Louthrenoo W, Chen YH, Cho J, Lateef A, Hamijoyo L, Luo SF, Wu YJ, Navarra SV, Zamora L, Li Z, Sockalingam S, Katsumata Y, Harigai M, Hao Y, Zhang Z, Basnayake BMDB, Chan M, Kikuchi J, Takeuchi T, Bae SC, Oon S, O'Neill S, Goldblatt F, Ng KPL, Law A, Tugnet N, Kumar S, Tee C, Tee M, Ohkubo N, Tanaka Y, Yu D, Karyekar CS, Sing Lau C, Monk JA, Nikpour M, Hoi A, Morand EF; Asia-Pacific Lupus Collaboration. Lupus low disease activity state and remission and risk of mortality in patients with systemic lupus erythematosus: a prospective, multinational, longitudinal cohort study. Lancet Rheumatol. 2022 Dec;4(12):e822-e830. doi: 10.1016/S2665-9913(22)00304-6. Epub 2022 Oct 22.

  PMID: 38261390 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Eric Morand

  Monash University

  STUDY CHAIR

Central Study Contacts

Eric F Morand

CONTACT

+ 61 3 8572 2650; eric.morand@monash.edu

Rangi K KANDANE-RATHNAYAKE

CONTACT

+ 61 3 8572 2561; Rangi.Kandane-Rathnayake@monash.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 3, 2017
• Study Start: September 1, 2013
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2032
• Last Updated: December 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3); KR (1); CN (2); SR (1); AU (4); PH (2); HK (1); ID (1); SG (2); TH (1); TW (2)