Patients with systemic lupus erythematosus (SLE) who attain a low disease state have a lower risk of subsequent disease flares and accumulated organ damage, making this state a potential treatment target in clinical trials, a new study suggests.
The research was published in an article, “Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study,” in the journal Lancet Rheumatology.
In SLE and other diseases that affect multiple organs, defining a therapeutic goal has been challenging. Clinical trials often use disease remission as their primary goal, but lupus patients rarely achieve sustained remission with current therapies.
- have a SLE Disease Activity Index (SLEDAI)-2K of 4 or lower, with no disease activity in major organ systems.
- show no additional signs of disease since their last assessment.
- achieve a SELENA-SLEDAI physician global assessment of 1 or less, where 0 represents no disease activity and 3 equals maximum disease activity.
- take no more than 7.5 milligrams of an immunosuppressant (prednisolone or similar).
- tolerate standard maintenance doses of immunosuppressants or approved biologic medicines.
LLDAS is currently being tested as an endpoint, or goal, in SLE clinical trials, but evidence showing its link with improved patient outcomes is still required before it’s used as a treatment goal.
A retrospective study has shown that attaining LLDAS leads to major reductions in healthcare use and cost, making it a cost-effective endpoint.
Subsequently, these same researchers — from Monash University, in Melbourne, Australia, and their colleagues — conducted a prospective study (NCT03138941) to assess whether achieving LLDAS protected lupus patients against flares and accrual (accumulation) of damage.
The trial, which is still enrolling participants, included 1,707 SLE patients, 93% women, from more than 13 centers of the Asia Pacific Lupus Collaboration in eight countries. Diagnosed at the mean average age of 29, the patients were observed in regular visits that were less than six months apart over 2.2 years.
At the start of the study, the median SLEDAI-2K score was 4, but 506 (29.6%) patients had a score of 6 or higher, which meant they had active disease. Organ damage was present in 706 (41.4%) of the patients.
LLDAS status was achieved in 6,081 visits (47.9%), with 1,332 patients (78%) having at least one episode of LLDAS during follow-up. Sustained LLDAS — defined as LLDAS for at least two consecutive visits — was achieved by 1,071 patients (62.7%), with half of them maintaining LLDAS for at least one year.
Achieving LLDAS at any visit was linked with a significant reduction of flares in the following visit. Damage accumulation was seen in 17.8% of patients who never experienced sustained LLDAS, and in 2.9% of those who achieved this state, reflecting a statistical significant difference.
Also, the data showed that the longer the sustained LLDAS, the lower the risk for new damage. In particular, patients who experienced LLDAS over at least 50% of the follow-up period had significant lower: flare and damage accumulation, SLEDAI-2K scores at the study’s start, mean prednisolone dose in follow-up, and likelihood to have vasculitis — blood vessel inflammation — or renal disease compared with those who spent less time in LLDAS.
Of note, the association between LLDAS and reduced damage accumulation was independent of previous damage or disease activity at baseline.
Overall, “LLDAS attainment is associated with significant protection against flare and damage accrual in SLE,” the scientists wrote.
“This large prospective study sets a benchmark for validation of lupus endpoints, and provides formal validation of LLDAS as a desirable treatment endpoint for lupus,” he added. “We look forward to LLDAS being adopted in treat-to-target approaches and trials of new medicines.”
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