Methotrexate Polyglutamate Concentrations as a Possible Predictive Marker for Effectiveness of Methotrexate Therapy in Patients with Sarcoidosis: A Pilot Study.

IF 4.6 2区 医学 Q1 RESPIRATORY SYSTEM
Lung Pub Date : 2023-12-01 Epub Date: 2023-11-16 DOI:10.1007/s00408-023-00656-0
Montse Janssen Bonás, Janani Sundaresan, Ruth G M Keijsers, Eduard A Struys, Bas J M Peters, Vivienne Kahlmann, Marlies S Wijsenbeek, Maurits C F J de Rotte, Jan C Grutters, Marcel Veltkamp
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引用次数: 0

Abstract

Introduction: Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG(n=1-5) resulting in enhanced cellular retention. In this study we address the question whether different MTXPG(n) concentrations in red blood cells (RBC) of patients with sarcoidosis after 3 months of MTX therapy correlate with response to treatment.

Methods: We retrospectively included patients with sarcoidosis that had started on MTX therapy and from whom blood samples and FDG-PET/CT were available 3 and 6-12 months after MTX initiation, respectively. FDG-uptake was measured by SUVmax in the heart, lungs and thoracic lymph nodes. Changes in SUVmax was used to determine anti-inflammatory response after 6-12 months of MTX therapy. MTXPG(n) concentrations were measured from whole blood RBC using an LC-MS/MS method. Pearson correlation coefficients were calculated to evaluate the relationship between changes in the SUVmax and MTXPG(n) concentrations.

Results: We included 42 sarcoidosis patients treated with MTX (15 mg/week); 31 with cardiac sarcoidosis and 11 with pulmonary sarcoidosis. In MTXPG3 and MTXPG4 a significant negative relation between the absolute changes in SUVmax and MTXPG(n) was found r = - 0.312 (n = 42, p = 0.047) for MTXPG3 and r = - 0.336 (n = 42, p = 0.031 for MTXPG4). The other MTXPG(n) did not correlate to changes in SUVmax.

Conclusion: These results suggest a relation between MTXPG(n) concentrations and the anti-inflammatory effect in patients with sarcoidosis. Further prospective validation is warranted, but if measuring MTXPG concentrations could predict treatment effect of MTX this would be a step in the direction of personalized medicine.

Abstract Image

甲氨蝶呤多谷氨酸浓度作为甲氨蝶呤治疗结节病有效性的可能预测指标:一项初步研究。
简介:甲氨蝶呤(MTX)是一种叶酸拮抗剂,常用于结节病患者的二线治疗。甲氨蝶呤的疗效有很大的患者间差异,目前尚不可能对甲氨蝶呤进行治疗性药物监测。给药后,MTX被主动运输到细胞中,并通过添加谷氨酸残基形成MTXPG(n=1-5)代谢成其活性形式,从而增强细胞保留。在这项研究中,我们探讨了结节病患者在接受MTX治疗3个月后,红细胞(RBC)中MTXPG(n)浓度的不同是否与治疗反应相关。方法:我们回顾性地纳入了开始MTX治疗的结节病患者,分别在MTX开始治疗3个月和6-12个月后获得血液样本和FDG-PET/CT。通过心脏、肺和胸淋巴结的SUVmax测量fdg的摄取。SUVmax的变化用于确定MTX治疗6-12个月后的抗炎反应。采用LC-MS/MS法测定全血红细胞MTXPG(n)浓度。计算Pearson相关系数来评价SUVmax与MTXPG(n)浓度变化之间的关系。结果:我们纳入了42例使用MTX (15mg /周)治疗的结节病患者;31例为心脏结节病,11例为肺结节病。MTXPG3和MTXPG4的SUVmax绝对值变化与MTXPG(n)呈显著负相关,分别为r = - 0.312 (n = 42, p = 0.047)和r = - 0.336 (n = 42, p = 0.031)。另一个MTXPG(n)与SUVmax的变化无关。结论:MTXPG(n)浓度与结节病患者的抗炎作用有关。进一步的前瞻性验证是必要的,但如果测量MTXPG浓度可以预测MTX的治疗效果,这将是个性化医疗方向的一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Lung
Lung 医学-呼吸系统
CiteScore
9.10
自引率
10.00%
发文量
95
审稿时长
6-12 weeks
期刊介绍: Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.
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