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Original Research: Diffuse Lung Disease |

Methotrexate vs Azathioprine in Second-line Therapy of SarcoidosisMethotrexate vs Azathioprine in Sarcoidosis

Adriane D. M. Vorselaars, MD; Wim A. Wuyts, MD, PhD; Veronique M. M. Vorselaars, MD; Pieter Zanen, MD, PhD; Vera H. M. Deneer, PhD; Marcel Veltkamp, MD, PhD; Michiel Thomeer, MD, PhD; Coline H. M. van Moorsel, PhD; Jan C. Grutters, MD, PhD
Author and Funding Information

From the Center of Interstitial Lung Diseases (Drs A. D. M. Vorselaars, V. M. M. Vorselaars, Veltkamp, van Moorsel, and Grutters), Department of Pulmonology, and Department of Clinical Pharmacy (Dr Deneer), St Antonius Hospital, Nieuwegein, The Netherlands; Unit for Interstitial Lung Diseases (Dr Wuyts), Department of Pulmonology, University Hospitals Leuven, Leuven, Belgium; Division of Heart and Lungs (Drs Zanen, van Moorsel, and Grutters), University Medical Centre Utrecht, Utrecht, The Netherlands; and the Department of Respiratory Medicine (Dr Thomeer), Hospital Oost Limburg, Research Cluster Oncology, UHasselt, Hasselt, Belgium.

Correspondence to: Jan C. Grutters, MD, PhD, Center of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands; e-mail: j.grutters@antoniusziekenhuis.nl


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(3):805-812. doi:10.1378/chest.12-1728
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Background:  Steroids remain the first-choice therapeutic in sarcoidosis; however, long-term use is associated with toxicity. Evidence defining the best second-line therapeutic is currently lacking. The aim of this study was to compare the effect of methotrexate and azathioprine on prednisone tapering, pulmonary function, and side effects in the second-line treatment of sarcoidosis.

Methods:  An international retrospective cohort study was performed, reviewing all patients with sarcoidosis who started methotrexate or azathioprine until 2 years after initiation or discontinuation. A linear mixed model with FEV1, vital capacity (VC), diffusing capacity of lung for carbon monoxide (Dlco), and prednisone dose changes over time as end points was used. Side effects were compared with χ2 tests.

Results:  Two hundred patients were included, of whom 145 received methotrexate and 55 azathioprine. Prednisone daily dose decreased a mean of 6.32 mg/y (P < .0001) while on therapy, with a similar steroid-sparing capacity for methotrexate and azathioprine. Of all patients completing 1 year of therapy, 70% had a reduction in daily prednisone dose of at least 10 mg. FEV1 showed a mean increase of 52 mL/y (P = .006) and VC of 95 mL/y (P = .001) in both treatment groups. Dlco % predicted increased, with a mean of 1.23%/y (P = .018). There were more patients with infections in the azathioprine group (34.6% vs 18.1%, P = .01), but no differences regarding other side effects.

Conclusions:  This retrospective study comparing the effect of second-line therapy in sarcoidosis shows that both methotrexate and azathioprine have significant steroid-sparing potency, a similar positive effect on lung function, and comparable side effects, except for a higher infection rate in the azathioprine group.

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