Lymphoma risk in systemic lupus: effects of treatment versus disease activity
Notice bibliographique
Résumé
We recently evaluated the risk of malignancy in SLE by linking a multi-site international SLE cohort with regional tumor registries. Across 28 centers, 15,980 patients were observed for 119,846 (average 7.5) person-years. In total, 641 cancers occurred, for an overall standardized incidence ratio (SIR) of 1.14 (95% CI = 1.06 to 1.24). Hematologic malignancies were substantially increased (SIR = 3.01, 95% CI = 2.47 to 3.62), particularly non-Hodgkin's lymphoma (NHL; SIR = 4.36, 95% CI = 3.43 to 5.47) and leukemia (SIR = 1.76, 95% CI = 1.04 to 2.78) [ 1 ]. Yet the relative influence of treatment versus disease activity is unknown. Our objective was to determine the relative importance of drugs versus disease activity in mediating the increased risk of lymphoma. We performed case-cohort analyses within this multi-site SLE cohort. Adjusted hazard ratios (HRs) for lymphoma were generated in multivariate regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarials, glucocorticoids), disease activity (mean adjusted SLEDAI-2K), demographics, calendar year, Sjögren's syndrome, and SLE duration. Partially adjusted models were also performed, using only covariates whose HR CI excluded the null. Sensitivity analyses were performed, lagging cyclophosphamide exposures by 5 years. Medications were treated both categorically (ever/never) and as cumulative doses. We studied 64 lymphomas (61 NHL, three Hodgkin's) and 4,739 cancer-free controls. As in the general population, lymphoma risk in SLE was higher in males and with age. Lymphomas occurred a mean of 13.1 years (standard deviation 9.8) after SLE diagnosis. Univariate analyses suggested a decreased lymphoma risk within the highest tertile of disease activity (relative to those with the lowest activity) but in fully adjusted models (using all variables listed above), the CI included the null (Table 1 ). Sensitivity analyses, lagging cyclophosphamide exposures, yielded similar results. In a partially adjusted model (retaining age and highest tertile of disease activity), the HR suggested a twofold lymphoma risk after cyclophosphamide. Despite a trend towards greater cyclophosphamide use in cases versus controls, in fully adjusted models, no drug was estimated to be an independent risk factor. Still, due to correlation, it remains difficult to differentiate the effects of medications from disease activity. We did not definitively demonstrate an increased risk for any medications, despite a trend to greater cyclophosphamide use in the lymphoma cases. If anything, we noted a protective effect for very high SLE disease activity. Further work will focus on genetic profiles that might interact with medication exposures to influence lymphoma risk in SLE.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».