Treat-to-target endpoints ‘feasible’ in lupus trials
medwireNews: The treat-to-target (T2T) endpoints of low disease activity (LDA), Lupus Low Disease Activity State (LLDAS), and remission are robust outcome measures for clinical trials in systemic lupus erythematosus (SLE), researchers report.
These findings are based on a post-hoc analysis of the phase 2b ADDRESS II trial, which previously demonstrated a potential benefit of the B cell inhibitor atacicept relative to placebo in people with more active disease according to various definitions, including those with high disease activity (HDA; SLEDAI-2K ≥10).
In the present study, Eric Morand (Monash University, Melbourne, Australia) and co-workers analyzed data from 158 ADDRESS II participants with HDA at baseline to investigate the proportions of patients meeting different response criteria.
As reported in Rheumatology, 55.1% of participants across the treatment arms achieved an SLE responder index (SRI)-4 response at week 24, while 42.4% had an SRI-6 response. For the T2T endpoints, 23.4% met the criteria for LDA (SLEDAI-2K≤2), 15.8% achieved LLDAS, and 10.8% achieved remission (cSLEDAI-2K=0).
Morand et al report that “almost all” patients who met the criteria for LDA, LLDAS, or remission also had an SRI-4 and an SRI-6 response, at 94.6%, 96.0%, and 100%, respectively. On the other hand, among patients with an SRI-4 response, only 40.2%, 27.6%, and 19.5% achieved LDA, LLDAS, or remission, respectively, as did a corresponding 52.2%, 35.8%, and 25.4% of those with an SRI-6 response.
“Thus, each of the T2T endpoints [was] significantly more stringent than SRI-4 and SRI-6,” they say.
Moreover, they note that all patients in remission additionally met the criteria for LLDAS, which is “consistent with the concept of these states being concentric.”
The investigators also demonstrated that a significantly higher proportion of HDA participants treated with atacicept versus placebo achieved LDA (37.3 vs 13.5%) or LLDAS (23.5 vs 5.8%) at week 24, in line with previously reported findings demonstrating significantly higher SRI-4 and SRI-6 response rates among atacicept-treated patients in this subgroup.
Together, these findings suggest that “LLDAS, LDA and remission are feasible endpoints in SLE trials, attainable in patients with highly active disease at baseline, which discriminate active treatment from placebo at week 24,” write the researchers.
“As new and more effective treatments emerge, following the example set in other rheumatic diseases, [T2T] approaches are likely to become part of the standard of care in SLE,” they add.
The study authors caution, however, that the hypothesis-generating findings from their study “must be confirmed by future testing in a formal T2T strategy trial.”
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