title: Methotrexate as a single agent for treating pulmonary sarcoidosis: a single centre real-life prospective study.
abstract: BACKGROUND
  The first-line therapy in chronic sarcoidosis, according to WASOG/ATS/ERS recommendations, is GCS. This therapy is associated with significant adverse effects and finally does not alter the natural history of the disease. The objective of our study was to evaluate the efficacy and safety of monotherapy with MTX, as an alternative to GCS, in progressive pulmonary sarcoidosis.
  
  
  METHODS
  An open prospective real-life, single-centre trial was performed on 50 patients with biopsy proven sarcoidosis, 28M and 22F, mean age 45.55 ± 8.9 years. The average duration of disease before MTX therapy was 12.34 ± 20.49 years, GCS therapy in the past was applied in 41 patients. All patients received MTX (10 mg or 15 mg weekly) between 2004 and 2013 because of chronic progressive pulmonary sarcoidosis. Therapy was planned for 24 months. Patients underwent regular clinical evaluation, pulmonary function assessment, exercise ability testing (6MWT), and chest radiography for therapy effectiveness every six months and side effects monitoring every 4-6 weeks. Forty-nine patients were included for statistical analysis of treatment efficacy. They were retrospectively allocated to "MTX responder" group if an improvement of 10% of FEV1, FVC, TLC, or 15% of DLCO from the initial value was documented for at least one parameter or "non-responders" if the patient did not meet the above-mentioned criteria.
  
  
  RESULTS
  Duration of treatment ranged from 6 to 24 months, mean time 60.75 ± 34.1 weeks. For the whole cohort significant improvement after MTX therapy was observed for minimal SaO2 (%) (p = 0.043) and for decrease of DSaO2 (%) (p = 0.048) in six-minute walk test. The results were significantly better for patients treated with 15 mg than for those treated with 10 mg weekly and for those who obtained a greater total amount of MTX during therapy. Significant difference of DLCO%pred was observed after six months of MTX therapy between groups treated 15 mg vs 10 mg weekly (73.27 ± 12.7% vs. 63.15 ± 16.4%, p = 0.03). Twenty-five patients (55%) met the criteria of "MTX responders" group. Patients who responded well to treatment had significantly lower TLC and FVC initial values comparing to "MTX non-responders". After treatment the only significant difference in PFT between groups was noted for DLCO%pred. Eleven patients (22%) stopped the treatment due to adverse events of MTX, mild hepatic abnormalities were observed in ten patients (20%), and concomitant infection was found in four patients. There were no patients with a fatal outcome.
  
  
  CONCLUSIONS
  MTX as a single agent in the treatment of sarcoidosis has proved to be a safe and effective steroid alternative. Selected patients with chronic pulmonary sarcoidosis experience definite PFT improvements after MTX treatment. There is need to search for predictors of MTX treatment effectiveness.
authors.affiliation: a.goljan@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Goljan-Geremek
authors.forename: Michał
authors.initials: M
authors.lastname: Bednarek
authors.forename: Monika
authors.initials: M
authors.lastname: Franczuk
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Puścińska
authors.forename: Adam
authors.initials: A
authors.lastname: Nowiński
authors.forename: Monika
authors.initials: M
authors.lastname: Czystowska
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kamiński
authors.forename: Damian
authors.initials: D
authors.lastname: Korzybski
authors.forename: Anna
authors.initials: A
authors.lastname: Stokłosa
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalska
authors.forename: Emil
authors.initials: E
authors.lastname: Wojda
authors.forename: Paweł
authors.initials: P
authors.lastname: Sliwiński
authors.forename: Barbara
authors.initials: B
authors.lastname: Burakowska
authors.forename: Jakub
authors.initials: J
authors.lastname: Ptak
authors.forename: Inga
authors.initials: I
authors.lastname: Barańska
authors.forename: Alicja
authors.initials: A
authors.lastname: Drygalska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Małek
authors.forename: Iwona
authors.initials: I
authors.lastname: Bestry
authors.forename: Stefan
authors.initials: S
authors.lastname: Wesołowski
authors.forename: Marek
authors.initials: M
authors.lastname: Kram
authors.forename: Dorota
authors.initials: D
authors.lastname: Górecka
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011446:Prospective Studies; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy*
chemical_list: D003879:Dermatologic Agents; D008727:Methotrexate