Adult definitions of low disease activity, remission in lupus achievable in children
Low disease activity and remission definitions used for adult systemic lupus erythematosus are achievable among children and can significantly reduce the risk for severe flare, according to data published in Rheumatology.
“A treat-to-target approach (T2T), where treatment is escalated until a specific target is achieved, and re-escalated if the target is lost, has been proposed as a strategy to improve adult-onset SLE (aSLE) outcomes,” Eve M.D. Smith, MD, BSc, PhD, of the University of Liverpool, in the United Kingdom, and colleagues wrote. “However, initiatives focusing on [childhood-onset SLE (cSLE)] are lacking. International principles and recommendations for T2T in aSLE have highlighted the need for validated remission and low disease activity (LDA) definitions, to enable a T2T approach.”
“A number of LDA definitions have been proposed, with the Asia Pacific Lupus Consortium producing the most widely accepted Lupus Low Disease Activity State (LLDAS) definition, based on the principle of ‘tolerable’ disease activity on stable treatment, with low corticosteroid doses and reduced likelihood of adverse outcomes,” they added. “Currently, no data robustly define appropriate cSLE T2T target(s).”
To analyze the achievability and impact of LDA or remission in childhood SLE, Smith and colleagues examined data from the United Kingdom Juvenile-onset SLE (UK JSLE) Cohort Study. According to the researchers, the UK JSLE study collects longitudinal data from 22 pediatric rheumatology centers. For their analysis, Smith and colleagues included 430 patients with childhood SLE from the cohort, all of whom had been monitored between 2006 and 2020, were aged 18 years or younger at diagnosis and fulfilled at least four American College of Rheumatology classification criteria.
All included patients, at recruitment and during follow-up visits, were assessed for demographics, including disease duration; ACR-SLE classification criteria; SLE disease activity, including full and clinical SLEDAI-2K scores and pBILAG2004 score; SLICC-ACR Damage Index (SDI) score; and blood and urine parameters. Smith and colleagues assessed the attainment of three adult SLE definitions of low disease activity:
- LLDAS, defined as a SLEDAI-2K score of four or less; no major active organ involvement, hemolytic anemia or gastrointestinal involvement; no new lupus features compared with previous assessment; physician global assessment (PGA) of no more than one; prednisolone dose of 7.5mg/day or less and no intravenous methylprednisolone; and tolerated standard maintenance immunosuppressive drugs or biological agents, excluding investigational drugs.
- LA, an altered version of LLDAS where the first criterion is limited to a SLEDAI-2K score of four or less, and the second criterion is excluded.
- Toronto-Low Disease Activity (Toronto-LDA), defined as a cSLEDAI-2K score of less than three, only one manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis, fever, thrombocytopenia, leukopenia; no corticosteroids; and no immunomodulators. Antimalarials are permitted.
In addition, the researchers assessed four definitions of remission: Clinical-SLEDAI-defined remission on or off treatment, and pBILAG-defined remission on or off treatment.
According to the researchers, LLDAS, LA and Toronto-LDA targets were achieved in 67%, 73% and 32% of patients following a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA were achieved for a median of 23%, 31% and 19% of the total follow-up-time, respectively.
Remission on-treatment was more common — 61% for cSLEDAI-defined and 42% for pBILAG-defined — compared with remission off-treatment — 31% for cSLEDAI and 21% for pBILAG).
Achieving all target states, and disease duration of more than 1 year, significantly reduced the risk for severe flare (P < .001), the researchers wrote. In addition, as the cumulative time in each target increased, the risk for severe flare progressively reduced. Achieving LLDAS reduced the risk for severe flare more than LA or Toronto-LDA (P < .001). LLDAS attainment and all remission definitions led to a statistically comparable reduction in the risks for severe flare (P > .05). Additionally, the achievement of all targets reduced the risk for new damage (P < .05).
“We know that childhood lupus is in many ways more severe than adult SLE, with higher disease activity, increased steroid burden, faster rates of damage accrual and higher standardized mortality rates,” Smith told Healio. “This study suggests that institution of a T2T approach has real potential to improve outcomes in this severe and potentially life-threatening disease. A prospective clinical trial is now needed to test whether childhood lupus patients can actually be 'treated to target' and what the impact a T2T approach has on important clinical outcomes.”