Reduced organ damage and premature mortality for patients who achieve prolonged periods with low disease activity validates treat- to- target approach in lupus
By Professor Hans Nossent
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune condition of unclear causes of the disease and with wide-ranging manifestations. Despite developments in the field, SLE patients still face a threefold increase in mortality and score lower on health-related quality of life assessments.
A major cause of morbidity is the cumulative organ damage due to persistent inflammation. Higher levels of organ damage are seen with persistently high disease activity and have a profound impact on a patient’s quality of life, causing significant levels of disability and unemployment. This has led to a push to develop a treatment strategy that results in minimising disease activity with a consequent reduction in organ damage.
Treat-to-target (T2T) has been defined as “a strategy aimed to treat patients to a goal which is capable of improving disease outcome”. This approach is currently already accepted in the follow-up of patients with Rheumatoid and Spondyloarthritis.
Still, it has been harder to define for SLE as the ultimate target of disease remission is achieved in less than 10% of patients, regardless of the definition used. According to the international task force, DORIS (Definitions of Remission In SLE) recommended that “the treatment target in SLE should be, the lowest possible disease activity, measured by a validated lupus activity index and/or by specific organ markers”.
For the first time, a reduction in mortality has been demonstrated for patients with SLE who were able to maintain a low disease activity state (LLDAS- see definition below) for more than 50% of their time spent with the disease.
Dr Chanakya Sharma and colleagues from Sir Charles Gairdner Hospital and the University of Western Australia analysed outcomes for 206 patients with SLE who were followed up for more than ten years (median 125 months).
They showed that lupus patients who spend most of the time (more than 50%) in Lupus Low Disease Activity State (LLDAS-50) have reduced organ damage accrual and also a significantly reduced mortality rate compared to patients who do not achieve LLDAS-50.
Approximately one-third of patients (69, 33.5%) spent at least half of the follow-up time in LLDAS-50. For these patients, there was a significant 63% reduced risk of severe damage and a 69% reduced risk of in age and sex-adjusted mortality compared to those patients who did not achieve LLDAS-50.
Some benefits were also seen for patients who achieved LLDAS for only 30% of follow-up, with a significant reduction in mortality and a strong trend towards a decrease in risk of severe damage.
Achieving long term low disease activity even with the use of medication, will thus significantly reduce the risk for organ damage and premature death among SLE patients.
Dr Sharma and colleagues wrote in the US scientific journal Arthritis Care and Research1 that the powerful effect seen on lupus outcomes now validates a treat-to-target (T2T) approach using LLDAS by clinicians overseeing the management of lupus patients.
A Lupus patient is said to be in LLDAS when they meet the following:
- SLE Disease Activity Index (SLEDAI) -2K less than 4, with no activity in major organ systems and no haemolytic anaemia or gastrointestinal activity;
- No new features of lupus compared with the previous assessment;
- Physician global assessment (PGA, scale 0–3) less than1
- Current prednisolone (or equivalent) dose less than 7.5 mg daily
- Well tolerated standard maintenance doses of immunosuppressive drugs
- 1. Arthritis Care Res, 2020 Mar;72(3):447-451. doi: 10.1002/acr.23867
Sharma C, Raymond W, Eilertsen G, Nossent J. Association of Achieving Lupus Low Disease Activity State Fifty Percent of the Time With Both Reduced Damage Accrual and Mortality in Patients With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2020;72(3):447-451. doi:10.1002/acr.23867