Development of prediction model for alanine transaminase elevations during the first 6 months of conventional synthetic DMARD treatment.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 08 2023
09 08 2023
Historique:
received:
12
02
2023
accepted:
29
07
2023
medline:
11
8
2023
pubmed:
10
8
2023
entrez:
9
8
2023
Statut:
epublish
Résumé
Frequent laboratory monitoring is recommended for early identification of toxicity when initiating conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). We aimed at developing a risk prediction model to individualize laboratory testing at csDMARD initiation. We identified inflammatory joint disease patients (N = 1196) initiating a csDMARD in Turku University Hospital 2013-2019. Baseline and follow-up safety monitoring results were drawn from electronic health records. For rheumatoid arthritis patients, diagnoses and csDMARD initiation/cessation dates were manually confirmed. Primary endpoint was alanine transaminase (ALT) elevation of more than twice the upper limit of normal (ULN) within 6 months after treatment initiation. Computational models for predicting incident ALT elevations were developed using Lasso Cox proportional hazards regression with stable iterative variable selection (SIVS) and were internally validated against a randomly selected test cohort (1/3 of the data) that was not used for training the models. Primary endpoint was reached in 82 patients (6.9%). Among baseline variables, Lasso model with SIVS predicted subsequent ALT elevations of > 2 × ULN using higher ALT, csDMARD other than methotrexate or sulfasalazine and psoriatic arthritis diagnosis as important predictors, with a concordance index of 0.71 in the test cohort. Respectively, at first follow-up, in addition to baseline ALT and psoriatic arthritis diagnosis, also ALT change from baseline was identified as an important predictor resulting in a test concordance index of 0.72. Our computational model predicts ALT elevations after the first follow-up test with good accuracy and can help in optimizing individual testing frequency.
Identifiants
pubmed: 37558753
doi: 10.1038/s41598-023-39694-2
pii: 10.1038/s41598-023-39694-2
pmc: PMC10412531
doi:
Substances chimiques
Alanine Transaminase
EC 2.6.1.2
Antirheumatic Agents
0
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12943Informations de copyright
© 2023. Springer Nature Limited.
Références
Saag, K. G. et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Care Res. 59, 762–784. https://doi.org/10.1002/art.23721 (2008).
doi: 10.1002/art.23721
Visser, K. et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: Integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann. Rheum. Dis. 68, 1086–1093. https://doi.org/10.1136/ard.2008.094474 (2009).
doi: 10.1136/ard.2008.094474
pubmed: 19033291
Singh, J. A. et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 64, 625–639. https://doi.org/10.1002/acr.21641 (2012).
doi: 10.1002/acr.21641
Taimen, K., Eklund, K., Kaipiainen-Seppänen, O., Karjalainen, A. & Mäkinen, H. Reumalääkityksen laboratorioseuranta—Ohjeet päivitetty. Finn. Med. J. 74, 249–251 (2019).
Ledingham, J. et al. BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs. Rheumatology (Oxford) 56, 865–868. https://doi.org/10.1093/rheumatology/kew479 (2017).
doi: 10.1093/rheumatology/kew479
pubmed: 28339817
Busger op Vollenbroek, F. T. M., Doggen, C. J. M., Janssens, R. W. A. & Bernelot Moens, H. J. Dermatological guidelines for monitoring methotrexate treatment reduce drug-survival compared to rheumatological guidelines. PLoS ONE 13, e0194401. https://doi.org/10.1371/journal.pone.0194401 (2018).
doi: 10.1371/journal.pone.0194401
pubmed: 29570708
pmcid: 5865732
Schmajuk, G. et al. Identification of risk factors for elevated transaminases in methotrexate users through an electronic health record. Arthritis Care Res. 66, 1159–1166. https://doi.org/10.1002/acr.22294 (2014).
doi: 10.1002/acr.22294
Malley, T., Corfield, G., Fung, P., Heneghan, D. & Kitchen, J. Transaminitis and neutropenia are rare in patients on methotrexate: Evidence from a large cohort of inflammatory arthritis patients. Rheumatology (Oxford) 58, 2061–2062. https://doi.org/10.1093/rheumatology/kez168 (2019).
doi: 10.1093/rheumatology/kez168
pubmed: 31081042
Karlsson Sundbaum, J. et al. Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: A long-term follow-up of predictors, surveillance, and outcome in clinical practice. Int. J. Rheum. Dis. 22, 1226–1232. https://doi.org/10.1111/1756-185X.13576 (2019).
doi: 10.1111/1756-185X.13576
pubmed: 31012257
pmcid: 6767545
Kent, P. D., Luthra, H. S. & Michet, C. Jr. Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis. J. Rheumatol. 31, 1727–1731 (2004).
pubmed: 15338491
Mori, S. et al. Incidence, predictive factors and severity of methotrexate-related liver injury in rheumatoid arthritis: A longitudinal cohort study. Rheumatol. Adv. Pract. 4, rkaa020. https://doi.org/10.1093/rap/rkaa020 (2020).
doi: 10.1093/rap/rkaa020
pubmed: 33134809
pmcid: 7585403
Dirven, L. et al. Risk of alanine transferase (ALT) elevation in patients with rheumatoid arthritis treated with methotrexate in a DAS-steered strategy. Clin. Rheumatol. 32, 585–590. https://doi.org/10.1007/s10067-012-2136-8 (2013).
doi: 10.1007/s10067-012-2136-8
pubmed: 23224330
Mahmoudian, M., Venäläinen, M. S., Klén, R. & Elo, L. L. Stable iterative variable selection. Bioinformatics 37, 4810–4817. https://doi.org/10.1093/bioinformatics/btab501 (2021).
doi: 10.1093/bioinformatics/btab501
pubmed: 34270690
pmcid: 8665768
Venäläinen, M. S., Klén, R., Mahmoudian, M., Raitakari, O. T. & Elo, L. L. Easy-to-use tool for evaluating the elevated acute kidney injury risk against reduced cardiovascular disease risk during intensive blood pressure control. J. Hypertens. 38, 511–518. https://doi.org/10.1097/HJH.0000000000002282 (2020).
doi: 10.1097/HJH.0000000000002282
pubmed: 31977572
Venäläinen, M. S. et al. Improved risk prediction of chemotherapy-induced neutropenia-model development and validation with real-world data. Cancer Med. 11, 654–663. https://doi.org/10.1002/cam4.4465 (2022).
doi: 10.1002/cam4.4465
pubmed: 34859963
Therneau, T. & Grambsch, P. Modeling Survival Data: Extending the Cox Model (Springer, 2000).
doi: 10.1007/978-1-4757-3294-8
Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2009).
doi: 10.1007/978-0-387-98141-3
Friedman, J., Hastie, T. & Tibshirani, R. Regularization paths for generalized linear models via coordinate descent. J. Stat. Softw. 33, 1–22 (2010).
doi: 10.18637/jss.v033.i01
pubmed: 20808728
pmcid: 2929880
Kremer, J. M., Lee, R. G. & Tolman, K. G. Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. Arthritis Rheum. 32, 121–127. https://doi.org/10.1002/anr.1780320202 (1989).
doi: 10.1002/anr.1780320202
pubmed: 2920047
Jensen, P. & Skov, L. Psoriasis and obesity. Dermatology 232, 633–639. https://doi.org/10.1159/000455840 (2016).
doi: 10.1159/000455840
pubmed: 28226326
Li, W., Han, J. & Qureshi, A. A. Obesity and risk of incident psoriatic arthritis in US women. Ann. Rheum. Dis. 71, 1267–1272. https://doi.org/10.1136/annrheumdis-2011-201273 (2012).
doi: 10.1136/annrheumdis-2011-201273
pubmed: 22562978
Pakchotanon, R., Ye, J. Y., Cook, R. J., Chandran, V. & Gladman, D. D. Liver abnormalities in patients with psoriatic arthritis. J. Rheumatol. 47, 847–853. https://doi.org/10.3899/jrheum.181312 (2020).
doi: 10.3899/jrheum.181312
pubmed: 31615918
Torosian, K. et al. Psoriatic disease and non-alcoholic fatty liver disease shared pathogenesis review. Semin. Arthritis Rheum. 59, 152165. https://doi.org/10.1016/j.semarthrit.2023.152165 (2023).
doi: 10.1016/j.semarthrit.2023.152165
pubmed: 36716599
Conway, R., Low, C., Coughlan, R. J., O’Donnell, M. J. & Carey, J. J. Risk of liver injury among methotrexate users: A meta-analysis of randomised controlled trials. Semin. Arthritis Rheum. 45, 156–162. https://doi.org/10.1016/j.semarthrit.2015.05.003 (2015).
doi: 10.1016/j.semarthrit.2015.05.003
pubmed: 26088004
Solomon, D. H. et al. Adverse effects of low-dose methotrexate: A randomized trial. Ann. Intern. Med. 172, 369–380. https://doi.org/10.7326/M19-3369 (2020).
doi: 10.7326/M19-3369
pubmed: 32066146
pmcid: 7229518