Efficacy and Tolerability of Methotrexate and Methylprednisolone in a Comparative Assessment of the Primary and Long-Term Outcomes in Patients with Pulmonary Sarcoidosis

Abstract

Background: There is insufficient information in the literature on the comparative efficacy and tolerability of methotrexate (MTX) and methylprednisolone (MP) in patients with pulmonary sarcoidosis in assessing primary outcomes and the relapse rate. Purpose: The aim of our study was to evaluate primary and long-term outcomes of using MTX and MP in patients with pulmonary sarcoidosis. Methods: A total of 143 patients with newly diagnosed pulmonary sarcoidosis, verified by high-resolution computed tomography (CT) data, were examined. Corticosteroid (CS) therapy was used in 97 patients using MP at a dose of 0.4 mg/kg body weight for 4 weeks, followed by a dose reduction to 0.1 mg/kg by the end of the sixth month. The total duration of CS therapy was 12 months on average. Forty-six patients were treated with MTX at a dose of 10 mg/week (28) and 15 mg/week (18) per os for 6 to 12 months. The study of the relapse rate was conducted within 12 months after the CT data normalization in 60 patients after CS therapy and in 24 after MTX treatment. Results: MP treatment was successfully completed in 68 (70.1%), and MTX in 29 (60.4%) patients. In five MP patients (5.2%) and in five (10.9%) MTX, treatment was discontinued due to serious side effects. In seven (7.2%) MP patients and ten (21.7%) MTX patients, treatment required additional therapy due to the lack of efficacy. Progression with MP treatment (17–17.5%) was more common than with MTX (2–4.3%; Chi square = 4.703, p = 0.031). Relapses after MP therapy were observed in 26 (43.3%) patients, and after MTX therapy in 2 (8.3%; Chi square = 9.450, p = 0.003). Conclusion: In patients with pulmonary sarcoidosis, MTX monotherapy does not differ significantly from MP monotherapy in terms of the level of efficacy and the rate of serious side effects. Increasing the MTX dose from 10 to 15 mg/week accelerates the rate of regression of sarcoidosis, improves treatment efficacy, and does not affect the rate of serious side effects. When using MTX, there is a significant decrease in the incidence of treatment resistance and the relapse rate.

Comparative Effectiveness of Methotrexate versus Methylprednisolone in Treatment Naïve Pulmonary Sarcoidosis Patients

“…In the current issue of the journal, Gavrysyuk et al use real-world evidence [18], obtained from an observational study of 143 newly diagnosed pulmonary sarcoidosis patients, including 45 (31.5%) with extrapulmonary manifestation and 29 (20%) with moderate/severe disease, to demonstrate same rates of treatment completion and sideeffects in head-to-head comparison of methylprednisolone (MP) and methotrexate (MTX). In their study, 97 (68%) enrolled patients were assigned to MP and the remaining 46 patients who could not tolerate corticosteroids for a variety of reasons, such as diabetes mellitus and obesity, were assigned to MTX.…”

“…What is noteworthy too is that most of the gains in the steroid-sparing regimens were realized in patients who received higher doses of MXT at 15 mg/week, while 9/10 failures (those who failed to demonstrate treatment effectiveness on radiological examination) were in those who received lower dose: 10 mg/week of MXT. In the words of the authors, "MXT monotherapy did not significantly differ with MP monotherapy, in effectiveness and in serious side effects" [18]. Indeed, the group from Kyiv must be commended for their hard work, clinical competency and the timely release of these data that will certainly enhance the care of sarcoidosis patients.…”

“…However, in addition to serial imaging (high-resolution CT scans), serial changes in symptoms, physiologic and pulmonary function, as well as other HRQoL measures are required and necessary when tracking disease progression. Gavrysyuk et al reported symptoms and CT imaging only [18]. All clinical observations are important, and they give us valuable insights about a disease we still know little about during therapy.…”

“…Meanwhile, 16-weeks of the CLEAR regimen (NCT02024555) failed to improve forced vital capacity (−1.1% versus 0.02%, p = 0.64), radiography, HRQoL or the 6-min walk distance when compared to placebo [23]. Thus, the work to better describe the relationships between pharmacotherapeutics and patients' response; such as drug dose responses and identifying optimal exposures associated with patients' outcomes, as demonstrated with MXT in the study by Gavrysyuk et al [18], still lies ahead of us. These critiques do not in any way diminish the findings by Gavrysyuk et al [18].…”

“…Thus, the work to better describe the relationships between pharmacotherapeutics and patients' response; such as drug dose responses and identifying optimal exposures associated with patients' outcomes, as demonstrated with MXT in the study by Gavrysyuk et al [18], still lies ahead of us. These critiques do not in any way diminish the findings by Gavrysyuk et al [18]. What is more reassuring is that there are similar findings reported by the same group previously, and related findings by others [7][8][9].…”