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Record W4386278277 · doi:10.1136/lupus-2023-la.26

26 Optimizing steroid-sparing drugs in SLE

2023· article· en· W4386278277 on OpenAlexaboutno aff
Guillermo Ruiz‐Irastorza

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicSystemic Lupus Erythematosus Research
Canadian institutionsnot available
Fundersnot available
KeywordsHydroxychloroquineCyclophosphamideMedicineAzathioprineSystemic lupus erythematosusPrednisoloneDrugPharmacologyLupus erythematosusMethotrexateClinical trialInternal medicineDiseaseImmunologyChemotherapyCoronavirus disease 2019 (COVID-19)

Abstract

fetched live from OpenAlex

Glucocorticoids (GC) have long been one of the cornerstones of the treatment of systemic lupus erythematosus (SLE). However, it is now a well-established fact that GC are a major cause of irreversible damage.1 Therefore, strategies to decrease GC load without compromising the adequate control of disease activity are essential in the management of SLE. Hydroxychloroquine (HCQ) should be considered the main GC-sparing drug in lupus. Its continued use has been associated to a myriad of beneficial effects, including the prevention of damage accrual and the improvement of survival, but also to a better control of lupus activity and, thus, a reduced need for GC use. Also, immunosuppressive drugs such as cyclophosphamide, azathioprine and methotrexate, have been extensively used throughout different clinical scenarios in order to decrease GC doses.2 Although clinical trials with this group of drugs are few, their use has long been validated by clinical practice. More recently, biologic agents approved for SLE such as belimumab and anifrolumab have also been shown to allow a good control of disease activity whilst reducing the dose of GCs.3 4 However, it is my view that the best GC-sparing drugs are…GCs. Pulses of methyl-prednisolone (MP), 125–500 mg/d, given for short periods of time (usually 3 days) have been shown to be the most effective way of rapidly controlling lupus flares through the activation of the non-genomic pathway.5 6 Therefore, the use of MP in the induction of remission, not only in life-threatening scenarios, combination therapy with HCQ and immunosuppressive drugs and a rapid tapering with a slow withdrawal of prednisone is our proposal for the successful management of SLE. In cases in which this scheme fails to adequately control lupus activity, the addition of biologic drugs should be considered. References Ugarte-Gil MF, et al. Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies. Lupus Sci Med. 2021 Dec;8(1):e000590. doi: 10.1136/lupus-2021-000590. Pego-Reigosa JM, et al. Efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus: a systematic review. Arthritis Care Res. (Hoboken). 2013 Nov;65(11):1775–85. doi: 10.1002/acr.22035. Touma Z, et al. Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada Study. Rheumatol Int. 2017 Jun;37(6):865–873. doi: 10.1007/s00296-017-3682-9. Epub 2017 Mar 9. Bruce IN, et al. Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials. Rheumatology (Oxford). 2023 Apr 3;62(4):1526–1534. doi: 10.1093/rheumatology/keac491. Ruiz-Irastorza G, et al. Prolonged remission in SLE is possible by using reduced doses of prednisone: an observational study from the lupus-cruces and lupus-bordeaux inception cohorts. Autoimmun Rev. 2019 Sep;18(9):102359. doi: 10.1016/j.autrev.2019.102359. Epub 2019 Jul 16. Ruiz-Irastorza G, Bertsias G. Treating systemic lupus erythematosus in the 21st century: new drugs and new perspectives on old drugs. Rheumatology (Oxford). 2020 Dec 5;59(Suppl5):v69-v81. doi: 10.1093/rheumatology/keaa403. Learning Objectives Describe the concept and the need for sparing GC Describe different drugs used to treat SLE with a GC-sparing effect Discuss results from recent studies on the efficacy and toxicity of therapeutic schemes using methyl-prednisolone pulses followed by lower doses of prednisone in active lupus Describe practical guidelines for using glucocorticoid-sparing drugs in the different settings of active lupus

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.007
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0070.002

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.

Opus teacher head0.044
GPT teacher head0.332
Teacher spread0.288 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreOther

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".

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Citations1
Published2023
Admission routes1
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