PReS-endorsed International Childhood Lupus T2T Task Force Definition of Childhood Lupus Low Disease Activity State (cLLDAS)

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2023 Mar 19

PMID 36934849

Authors

E M D Smith

A Aggarwal

J Ainsworth

E Al-Abadi

T Avcin

L Bortey

J Burnham

C Ciurtin

C M Hedrich

S Kamphuis

L Lambert

D M Levy

L Lewandowski

N Maxwell

E Morand

S Ozen

C E Pain

A Ravelli

C Saad Magalhaes

C Pilkington

D Schonenberg-Meinema

C Scott

K Tullus

M W Beresford

Affiliations

Soon will be listed here.

Abstract

Objective: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials.

Methods: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria.

Results: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics.

Conclusions: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

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References

Ugarte-Gil M, Wojdyla D, Pons-Estel G, Catoggio L, Drenkard C, Sarano J . Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL). Ann Rheum Dis. 2017; 76(12):2071-2074. DOI: 10.1136/annrheumdis-2017-211814. View

Apostolopoulos D, Kandane-Rathnayake R, Louthrenoo W, Luo S, Wu Y, Lateef A . Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study. Lancet Rheumatol. 2024; 2(1):e24-e30. DOI: 10.1016/S2665-9913(19)30105-5. View

Smith E, Gorst S, Al-Abadi E, Hawley D, Leone V, Pilkington C . 'It is good to have a target in mind': qualitative views of patients and parents informing a treat to target clinical trial in juvenile-onset systemic lupus erythematosus. Rheumatology (Oxford). 2021; 60(12):5630-5641. PMC: 8645274. DOI: 10.1093/rheumatology/keab173. View

Ter Haar N, van Dijkhuizen E, Swart J, Royen-Kerkhof A, El Idrissi A, Leek A . Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol. 2019; 71(7):1163-1173. PMC: 6617757. DOI: 10.1002/art.40865. View

van Vollenhoven R, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrom K . Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014; 73(6):958-67. DOI: 10.1136/annrheumdis-2013-205139. View

Ozturk K, Caglayan S, Tanatar A, Baglan E, Yener Otar G, Kavrul Kayaalp G . Low disease activity state in juvenile-onset systemic lupus erythematosus. Lupus. 2021; 30(13):2144-2150. DOI: 10.1177/09612033211054399. View

van Vollenhoven R, Voskuyl A, Bertsias G, Aranow C, Aringer M, Arnaud L . A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2016; 76(3):554-561. DOI: 10.1136/annrheumdis-2016-209519. View

Polachek A, Gladman D, Su J, Urowitz M . Defining Low Disease Activity in Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2016; 69(7):997-1003. DOI: 10.1002/acr.23109. View

Tani C, Vagelli R, Stagnaro C, Carli L, Mosca M . Remission and low disease activity in systemic lupus erythematosus: an achievable goal even with fewer steroids? Real-life data from a monocentric cohort. Lupus Sci Med. 2018; 5(1):e000234. PMC: 5844382. DOI: 10.1136/lupus-2017-000234. View

10.

Hissink Muller P, Brinkman D, Schonenberg-Meinema D, van den Bosch W, Koopman-Keemink Y, Brederije I . Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial. Ann Rheum Dis. 2018; 78(1):51-59. DOI: 10.1136/annrheumdis-2018-213902. View

11.

Tsang-A-Sjoe M, Bultink I, Heslinga M, Voskuyl A . Both prolonged remission and Lupus Low Disease Activity State are associated with reduced damage accrual in systemic lupus erythematosus. Rheumatology (Oxford). 2016; 56(1):121-128. DOI: 10.1093/rheumatology/kew377. View

12.

Smith E, Aggarwal A, Ainsworth J, Al-Abadi E, Avcin T, Bortey L . Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force. Ann Rheum Dis. 2023; 82(6):788-798. PMC: 10314055. DOI: 10.1136/ard-2022-223328. View

13.

Eastman R, Keen H . The impact of cardiovascular disease on people with diabetes: the potential for prevention. Lancet. 1997; 350 Suppl 1:SI29-32. DOI: 10.1016/s0140-6736(97)90026-x. View

14.

Zen M, Iaccarino L, Gatto M, Saccon F, Larosa M, Ghirardello A . Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission. Ann Rheum Dis. 2017; 77(1):104-110. DOI: 10.1136/annrheumdis-2017-211613. View

15.

Petri M, Magder L . Comparison of Remission and Lupus Low Disease Activity State in Damage Prevention in a United States Systemic Lupus Erythematosus Cohort. Arthritis Rheumatol. 2018; 70(11):1790-1795. PMC: 6203602. DOI: 10.1002/art.40571. View

16.

Parra Sanchez A, Voskuyl A, van Vollenhoven R . Treat-to-target in systemic lupus erythematosus: advancing towards its implementation. Nat Rev Rheumatol. 2022; 18(3):146-157. DOI: 10.1038/s41584-021-00739-3. View

17.

Smith E, Tharmaratnam K, Al-Abadi E, Armon K, Bailey K, Brennan M . Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus. Rheumatology (Oxford). 2021; 61(8):3378-3389. PMC: 9348762. DOI: 10.1093/rheumatology/keab915. View

18.

Brunner H, Gladman D, Ibanez D, Urowitz M, Silverman E . Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008; 58(2):556-62. DOI: 10.1002/art.23204. View

19.

Chessa E, Piga M, Floris A, Devilliers H, Cauli A, Arnaud L . Use of Physician Global Assessment in systemic lupus erythematosus: a systematic review of its psychometric properties. Rheumatology (Oxford). 2020; 59(12):3622-3632. DOI: 10.1093/rheumatology/keaa383. View

20.

Heshin-Bekenstein M, Trupin L, Yelin E, von Scheven E, Yazdany J, Lawson E . Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus. Semin Arthritis Rheum. 2019; 49(2):267-272. PMC: 7480934. DOI: 10.1016/j.semarthrit.2019.05.010. View