Risk factors associated with delayed methotrexate clearance and increased toxicity in pediatric patients with osteosarcoma
PEDIATRIC BLOOD & CANCER
Authors: Young, Elizabeth P.; Cheng, W. Susan; Bernhardt, Melanie B.; Wang, Lisa L.; Rainusso, Nino; Foster, Jennifer H.
High-dose methotrexate (HD-MTX; 12 g/m(2)) is part of standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. We investigated the association between peak MTX levels (four-hour) and delayed MTX clearance or treatment toxicity. Information was retrieved from electronic medical records of 33 OS patients treated with HD-MTX at Texas Children's Hospital from 2008 to 2015. We found that the four-hour MTX level did not contribute to toxicity or delayed MTX clearance. We demonstrated that certain demographic characteristics are associated with delayed clearance and increased toxicity.
Achieving sustained minimal disease activity with methotrexate in early interleukin 23-driven early psoriatic arthritis
Authors: den Braanker, Hannah; Wervers, Kim; Mus, Adriana M. C.; Bangoer, Priyanka S.; Davelaar, Nadine; Luime, Jolanda; Tchetverikov, Ilja; Hazes, J. M. W.; Vis, Marijn; Lubberts, Erik; Kok, Marc R.
Objectives Methotrexate (MTX) is currently the recommended first-line therapy for treating psoriatic arthritis (PsA), despite lacking clear evidence. No estimates of efficacy of MTX in usual care and no clear MTX responsive clinical or laboratory variables are currently available. This study describes the response to MTX monotherapy in newly diagnosed patients with PsA in usual care. Second, we compared clinical variables and cytokine profiles in patients responding and not responding to MTX monotherapy. Methods We used data collected in the Dutch southwest Early Psoriatic Arthritis cohoRt study to select patients with PsA with oligoarthritis or polyarthritis, and at least 1 year follow-up. We analysed disease activity at 6 months of patients who started MTX monotherapy and still used MTX monotherapy 1 year after diagnosis. Cytokine profiles were determined at baseline and after 3 and 6 months with a bead-based multi-immunoassay. Results We identified 219 patients of which 183 (84%) patients started MTX monotherapy within 6 months after diagnosis. 90 patients used MTX monotherapy throughout the first year of which 44 patients (24%) reached minimal disease activity(MDA) at 6 months, decreasing to 33 patients (18%) after 1 year. Non-responders had significantly higher concentrations of interleukin (IL) 23 and IL-10 before and during MTX therapy. Conclusions Our results showed that only 18% of patients with PsA are in sustained MDA after 1 year of MTX monotherapy and non-responders more often had IL-23driven disease. Our results indicate the need for more treatto-target and personalised therapy strategies in PsA.