Effects of atacicept on disease activity in patients with moderate to severe systemic lupus erythematosus: APRIL-SLE randomized trial
Bibliographic record
Abstract
Atacicept is a fusion protein that inhibits B-cell stimulating factors BLyS and APRIL, which are elevated in systemic lupus erythematosus (SLE). Atacicept 150 mg (A150) was associated with reduced BILAG A and B flares in the APRIL-SLE study. We examined efficacy of atacicept in preventing flares of SLE disease activity by the BILAG organ system and modified SELENA SLEDAI flare index and assessed corticosteroid use during a previously reported trial of atacicept versus placebo (PLC). Subjects with active SLE were treated with corticosteroid taper for 12 weeks. Subjects reaching BILAG C or D at weeks 10 and 12 were randomized at baseline 1:1:1 to receive PLC, atacicept 75 mg (A75) or A150 twice weekly every 4 weeks then weekly for 48 weeks. All patients received standard of care. Analysis was performed in the modified intention-to-treat population. BILAG and SELENA SLEDAI flares and corticosteroid usage were assessed 4 weekly. The A150 arm was terminated early due to two fatal pulmonary infections. A lower proportion of subjects with >1 BILAG system A or B flare was observed in A150 and A75 versus PLC. Proportions of subjects with BILAG flare in each organ system were reduced in A150 versus PLC, except for vasculitis, which had similar proportions between groups. BILAG flares were most commonly observed in mucocutaneous and musculoskeletal systems. Proportions of subjects with severe SELENA SLEDAI flare during treatment in a post-hoc analysis were 19%, 11%, and 13% for PLC, A75, and A150, respectively. There was a dose-proportional decrease in the number of subjects who had at least one increase in steroid dose, and an increase of ≥20 mg/day (Table 1 ). Atacicept induced substantial reductions in Ig levels, which lessened during follow-up but did not fully return to baseline over 24 weeks. Atacicept treatment effect was observed in subjects with BLyS or APRIL levels ≥ median, but not < median. The difference was most pronounced in patients with baseline BLyS and APRIL ≥ median. Atacicept-treated patients with greatest absolute decrease in IgG and IgM experienced fewest new flares. Reduction of the individual BILAG system and severe SELENA SLEDAI flares and corticosteroid use was associated with A150 treatment. Analysis of potential predictive biomarkers identified a subgroup of patients with higher BLyS and APRIL levels at baseline more likely to benefit from treatment. Further studies are required to clarify safety and efficacy of atacicept in SLE patients and associations between biomarkers and clinical response to atacicept.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".