REFRACTORY PULMONARY SARCOIDOSIS: INCIDENCE AFTER TREATMENT WITH METHYLPREDNISOLONE AND/OR METHOTREXATE IN PATIENTS WITH NEWLY DIAGNOSED DISEASE.

Pulmonary sarcoidosis is considered refractory if glucocorticoids (GCs) at a maintenance dose of at least 10 mg/day (prednisolone equivalent) and methotrexate (MTX), including their combined use, are not effective enough to achieve clinical remission. Aim - to study the rate of refractory pulmonary sarcoidosis after conventional treatment with methylprednisolone (MP) and/or MTX in patients with newly diagnosed disease. 250 patients with newly diagnosed pulmonary sarcoidosis (106 men and 144 women; mean age 44 years) were examined. Radiological stage II was established in 237 (94.8%) patients, stage III - in 13 (5.2%). GCs therapy was carried out using MP in 190 patients at an initial dose of 0.4 mg/kg/day for 4 weeks with a gradual decrease to a maintenance dose (0.1 mg/kg/day) by the end of the 6th month. In the presence of contraindications or serious adverse effects of MP (60 patients), MTX was used at a dose of 15 mg/week. Patients without contraindications and serious adverse effects of MP treated with MTX, in case of initial therapy failure, were prescribed combined therapy with MP (12 mg/day) and MTX (10 mg/week). Based on combination therapy outcomes, as well as taking into account the cases of MTX therapy failure in patients with contraindications or serious adverse effects of GCs therapy, refractory pulmonary sarcoidosis was diagnosed in 27 (10.8%) patients. Patients with refractory pulmonary sarcoidosis were more likely to have stage III disease (Pearson's χ2 test=5.766, p=0.018), as well as extrapulmonary lesions (χ2 test=4.672, p=0.031). The high rate of conventional therapy failure using first- and second-line medications in patients with newly diagnosed sarcoidosis determines the relevance of further study of the causes, development of risk criteria and new approaches to the treatment of refractory pulmonary sarcoidosis.

[EFFECTIVENESS AND SAFETY OF METHOTREXATE MONOTHERAPY IN PATIENTS WITH PULMONARY SARCOIDOSIS].

Immunosuppressants are traditionally administered in sarcoidosis patients with contraindications for the use of glucocorticosteroids (GCS), or in those with serious adverse reactions on GCS, as well as in the cases of GCS-therapy resistance. Aim - to study the effectiveness and safety of methotrexate monotherapy in pulmonary sarcoidosis patients with either GCS contraindication or adverse reactions. We examined 33 patients with st. II pulmonary sarcoidosis, 20 men and 13 women, 23-67 years of age. In all cases a general physical examination; chest computed tomography and spirometry were performed. Oral methotrexate 10 mg once per week was administered to all patients. Blood tests, including total blood count with platelet count, blood chemistry (ALT, AST, bilirubin, creatinin) were done before the start of the therapy and monthly afterwards. Methotrexate monotherapy appeared to be effective in 24 (72,7%) study patients (clinical cure or regression of lung lesions). Adverse reactions were registered in 10 (30,3%) patients. In 1 case treatment was stopped because of the serious adverse event. As it was confirmed by our study results, methotrexate should be considered a medication of choice in pulmonary sarcoidosis patients with contraindications for use or adverse reactions to GCS. A research of combination therapy of methotrexate with first-line drugs should be continued.