MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.
The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.
“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
Urgent need to improve childhood lupus outcomes
“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.
“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.
Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.
“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.
The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.
Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.
T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
The cSLE T2T international task force and cLLDAS definition
With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.
“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”
Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.
Next, they looked to develop an age-appropriate definition for low disease activity.
“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.
The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”
The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.
“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.
The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.
The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.