03 Disease modification and prevention of damage
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
<h3></h3> Although there is currently a need to adopt a treat to target approach in systemic lupus erythematosus (SLE), there are no clear descriptions of disease modifications to guide this approach. Recently van Vollenhoven <i>et al</i> reported a conceptual framework for defining disease modification in SLE in three epochs, year 1, years 2–5, and ≥5 years.<sup>1</sup> They suggested criteria to define disease modification for each epoch including minimizing disease activity and slowing or preventing organ damage progression.<sup>1</sup> Failure to achieve these disease modifications results in damage accrual either due to the disease or its treatment. Furthermore, damage accrual predicts increasing damage and mortality.<sup>2 3</sup> Very few of the therapeutic agents currently available to treat SLE have been successful in disease modification in all three epochs either because their therapeutic effect is short lived, or they have not yet been used for ≥5 years or toxicity has precluded long term use. Four medications merit mention at this time: corticosteroids, antimalarials, belimumab and anifrolumab. Corticosteroids are very effective anti-inflammatory/anti-immunologic agents, but should not be used long term because of their significant toxicities. One should use a dose required to achieve suppression of the acute inflammatory clinical disease BUT strive to wean to a dose of ≤5 mg prednisone by 3 months. Time to achieve the clinical response desired may vary depending on disease manifestations, but rapid weaning should remain the desired target. With complete remission weaning the last 5 mg prednisone is possible, using a slow taper schedule.<sup>4</sup> Antimalarials used early and consistently have been shown to protect against damage accrual and mortality.<sup>2 3</sup> Belimumab, the first biologic developed for the treatment of SLE, was first approved in 2011 and has now been shown to be disease modifying in each of the three epochs with minimal toxicity. Belimumab’s long term use has demonstrated a reduction in organ damage progression, a slowed rate of organ damage progression and reduction in the magnitude of year-to-year organ damage.<sup>5</sup> Anifrolumab was approved by the FDA in 2021 but has data for 3 years of follow-up in an extension study that show the initial therapeutic responses persist. There is a lower cumulative corticosteroid dose in patients and there was no safety issue signal.<sup>6</sup> <h3>References</h3> van Vollenhoven R, <i>et al.</i> Conceptual framework for defining disease modification in systemic lupus erythematosus: a call for formal criteria. <i>Lupus Sci Med.</i> 2022 Mar;<b>9</b>(1):e000634. doi: 10.1136/lupus-2021-000634. Bruce IN, <i>et al.</i> Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the systemic lupus international collaborating clinics (SLICC) inception cohort. <i>Ann Rheum Dis</i>. 2015 Sep;<b>74</b>(9):1706–13. doi: 10.1136/annrheumdis-2013-205171. Rahman P, <i>et al</i>. Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus. <i>Lupus</i>. 2001;<b>10</b>(2):93–6. doi: 10.1191/096120301670679959. Tselios K, <i>et al.</i> Gradual glucocorticosteroid withdrawal is safe in clinically quiescent systemic lupus erythematosus. <i>ACR Open Rheumatol</i>. 2021 Aug;<b>3</b>(8):550–557. doi: 10.1002/acr2.11267. Epub 2021 Jul 10. Urowitz MB, <i>et al</i>. Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis. <i>Ann Rheum Dis</i>. 2019 Mar;<b>78</b>(3):372–379. doi: 10.1136/annrheumdis-2018-214043. Kalunian KC, <i>et al.</i> A randomized, placebo-controlled phase iii extension trial of the long-term safety and tolerability of anifrolumab in active systemic lupus erythematosus. <i>Arthritis Rheumatol.</i> 2023 Feb;<b>75</b>(2):253–265. doi: 10.1002/art.42392. Epub 2022 Nov 11. <h3>Learning Objectives</h3> Describe a definition of disease modification in SLE Describe that failure of disease modification results in significant damage Explain how managing corticosteroids, antimalarials and two newer biologics may aid damage prevention
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it