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Prolonged Use of Methotrexate for Sarcoidosis

Prolonged Use of Methotrexate for Sarcoidosis Abstract Background: To determine the safety and efficacy of methotrexate as a steroid-sparing agent in patients with symptomatic sarcoidosis, a nonrandomized interventional study of patients with chronic sarcoidosis treated with methotrexate for at least 2 years was performed. Efficacy was assessed for all patients after 2 years of treatment. Toxicity was assessed for all patients receiving therapy for the entire time (a total of 150 patient-years). Methods: Patients were treated in a subspecialty ambulatory clinic at a university hospital. Patients with biopsy-confirmed sarcoidosis who had persistent symptoms and who were eager to avoid or reduce corticosteroid therapy were selected for study. A total of 50 patients completed at least 2 years of methotrexate therapy. Patients were treated with oral methotrexate once a week. Dosage was adjusted based on the patient's white blood cell count. Clinical response was measured in the affected organ, including the lung (measurement of vital capacity), skin (regression of skin lesions), and central nervous system (magnetic resonance imaging). Also noted was the initial and subsequent dosage of prednisone used as therapy for sarcoidosis. Results: Improvement in vital capacity or other affected symptomatic organ was noted in 33 of 50 treated patients. Corticosteroids were discontinued in an additional six patients who remained stable with clinical or symptomatic improvement. The major toxic effects noted in 150 patient-years of therapy were hepatic (six patients), leukopenia requiring hospitalization (one patient), and cough (one patient). Forty-one liver biopsy procedures were performed in 33 patients. Of these, six demonstrated significant changes related to methotrexate that led to drug discontinuation. Conclusion: Methotrexate is a well-tolerated therapeutic agent with significant steroid sparing and efficacy for the treatment of chronic symptomatic sarcoidosis.(Arch Intern Med. 1995;155:846-851) References 1. Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med . 1983;208:525-533. 2. DeRemee RA. The present status of therapy of pulmonary sarcoidosis: a house divided. Chest . 1977;71:388-393.Crossref 3. Sharma OP. Pulmonary sarcoidosis and corticosteroids. Am Rev Respir Dis . 1993:147:1598-1600.Crossref 4. Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum . 1986;29:822-831.Crossref 5. Anderson PA, West SG, O'Dell JR, Via CS, Claypool RG, Kotzin BL. Weekly pulse methotrexate in rheumatoid arthritis. Ann Intern Med . 1985;103:489-496.Crossref 6. Lower EE, Baughman RP. The use of low dose methotrexate in refractory sarcoidosis. Am J Med Sci . 1990;299:153-157.Crossref 7. Baughman RP, Shipley R, Eisentrout CE. Predictive value of gallium scan, angiotensin-converting enzyme level, and bronchoalveolar lavage in 2-year follow-up of pulmonary sarcoidosis. Lung . 1987;165:371-377.Crossref 8. Johns CJ, Zachary JB, Ball WC. A 10-year study of corticosteroid treatment of pulmonary sarcoidosis. Johns Hopkins Med J . 1974;134:271-283. 9. Jones E, Cagen JP. Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas . J Am Acad Dermatol . 1990;23:487-490.Crossref 10. Pacheo Y, Marechal C, Marechal F, Biot N, Perrin-Fayolle M. Azathioprine treatment of chronic pulmonary sarcoidosis. Sarcoidosis . 1985;2:107-113. 11. Sharma OP, Hughes DTD, James DG, Naish P. Immunosuppressive therapy with azathioprine in sarcoidosis. In: Levinsky L, Macholoa F, eds. Fifth International Conference on Sarcoidosis and Other Granulomatous Disorders . Prague, Czech Republic: Universita Karlova; 1971:635-637. 12. Demeter SL. Myocardial sarcoidosis unresponsive to steroids: treatment with cyclophosphamide. Chest . 1988;94:202-203.Crossref 13. Kataria YP. Chlorambucil in sarcoidosis. Chest . 1980;78:36-42.Crossref 14. Lerner HJ. Acute myelogenous leukemia in patients receiving chlorambucil as long-term adjuvant chemotherapy for stage II breast cancer. Cancer Treat Rep . 1978;62:1135-1138. 15. Baker GL, Kahl LE, Zee BC, Stolzer BL, Agarwal AK, Medsger TA. Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Am J Med . 1987;83:1-9.Crossref 16. Balin PL, Tindall JP, Roenigk HH, Hogan MD. Is methotrexate therapy for psoriasis carcinogenic? a modified retrospective-prospective analysis. JAMA . 1975; 232:359-362.Crossref 17. Rustin GJS, Rustin F, Dent J, Booth M, Salt S. No increase in second tumors after cytotoxic chemotherapy for gestational trophoblastic tumors. N Engl J Med . 1982;308:473-476.Crossref 18. Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. J Rheumatol . 1985;12:S35-S39. 19. Lacher MJ. Spontaneous remission response to methotrexate in sarcoidosis. Ann Intern Med . 1968:69:1274-1278.Crossref 20. Fenton DA, Shaw M, Black MN. Invasive nasal sarcoidosis treated with methotrexate. Clin Exp Dermatol . 1985;10:279-283.Crossref 21. Israel HL The treatment of sarcoidosis. Postgrad Med J . 1970;46:537-540.Crossref 22. Tolman KG, Clegg DO, Lee RG, Ward JR. Methotrexate and the liver. J Rheumatol . 1985;12:S29-S34. 23. White DA, Rankin JA, Stover DE, Gellene RA, Gupta S. Methotrexate pneumonitis: bronchoalveolar lavage findings suggest an immunologie disorder. Am Rev Respir Dis . 1989;139:18-21.Crossref 24. Jones G, Mierins E, Karsh J. Methotrexate-induced asthma. Am Rev Respir Dis . 1991;143:179-181.Crossref 25. Mullarkey MF, Lammert JF, Blumenstein BA. Long-term methotrexate treatment in corticosteroid-dependent asthma. Ann Intern Med . 1990;112:577-581.Crossref 26. Lower EE, Smith JT, Martelo 0J, Baughman RP. The anemia of sarcoidosis. Sarcoidosis . 1988;5:51-55. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Prolonged Use of Methotrexate for Sarcoidosis

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1995.00430080088011
Publisher site
See Article on Publisher Site

Abstract

Abstract Background: To determine the safety and efficacy of methotrexate as a steroid-sparing agent in patients with symptomatic sarcoidosis, a nonrandomized interventional study of patients with chronic sarcoidosis treated with methotrexate for at least 2 years was performed. Efficacy was assessed for all patients after 2 years of treatment. Toxicity was assessed for all patients receiving therapy for the entire time (a total of 150 patient-years). Methods: Patients were treated in a subspecialty ambulatory clinic at a university hospital. Patients with biopsy-confirmed sarcoidosis who had persistent symptoms and who were eager to avoid or reduce corticosteroid therapy were selected for study. A total of 50 patients completed at least 2 years of methotrexate therapy. Patients were treated with oral methotrexate once a week. Dosage was adjusted based on the patient's white blood cell count. Clinical response was measured in the affected organ, including the lung (measurement of vital capacity), skin (regression of skin lesions), and central nervous system (magnetic resonance imaging). Also noted was the initial and subsequent dosage of prednisone used as therapy for sarcoidosis. Results: Improvement in vital capacity or other affected symptomatic organ was noted in 33 of 50 treated patients. Corticosteroids were discontinued in an additional six patients who remained stable with clinical or symptomatic improvement. The major toxic effects noted in 150 patient-years of therapy were hepatic (six patients), leukopenia requiring hospitalization (one patient), and cough (one patient). Forty-one liver biopsy procedures were performed in 33 patients. Of these, six demonstrated significant changes related to methotrexate that led to drug discontinuation. Conclusion: Methotrexate is a well-tolerated therapeutic agent with significant steroid sparing and efficacy for the treatment of chronic symptomatic sarcoidosis.(Arch Intern Med. 1995;155:846-851) References 1. Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med . 1983;208:525-533. 2. DeRemee RA. The present status of therapy of pulmonary sarcoidosis: a house divided. Chest . 1977;71:388-393.Crossref 3. Sharma OP. Pulmonary sarcoidosis and corticosteroids. Am Rev Respir Dis . 1993:147:1598-1600.Crossref 4. Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum . 1986;29:822-831.Crossref 5. Anderson PA, West SG, O'Dell JR, Via CS, Claypool RG, Kotzin BL. Weekly pulse methotrexate in rheumatoid arthritis. Ann Intern Med . 1985;103:489-496.Crossref 6. Lower EE, Baughman RP. The use of low dose methotrexate in refractory sarcoidosis. Am J Med Sci . 1990;299:153-157.Crossref 7. Baughman RP, Shipley R, Eisentrout CE. Predictive value of gallium scan, angiotensin-converting enzyme level, and bronchoalveolar lavage in 2-year follow-up of pulmonary sarcoidosis. Lung . 1987;165:371-377.Crossref 8. Johns CJ, Zachary JB, Ball WC. A 10-year study of corticosteroid treatment of pulmonary sarcoidosis. Johns Hopkins Med J . 1974;134:271-283. 9. Jones E, Cagen JP. Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas . J Am Acad Dermatol . 1990;23:487-490.Crossref 10. Pacheo Y, Marechal C, Marechal F, Biot N, Perrin-Fayolle M. Azathioprine treatment of chronic pulmonary sarcoidosis. Sarcoidosis . 1985;2:107-113. 11. Sharma OP, Hughes DTD, James DG, Naish P. Immunosuppressive therapy with azathioprine in sarcoidosis. In: Levinsky L, Macholoa F, eds. Fifth International Conference on Sarcoidosis and Other Granulomatous Disorders . Prague, Czech Republic: Universita Karlova; 1971:635-637. 12. Demeter SL. Myocardial sarcoidosis unresponsive to steroids: treatment with cyclophosphamide. Chest . 1988;94:202-203.Crossref 13. Kataria YP. Chlorambucil in sarcoidosis. Chest . 1980;78:36-42.Crossref 14. Lerner HJ. Acute myelogenous leukemia in patients receiving chlorambucil as long-term adjuvant chemotherapy for stage II breast cancer. Cancer Treat Rep . 1978;62:1135-1138. 15. Baker GL, Kahl LE, Zee BC, Stolzer BL, Agarwal AK, Medsger TA. Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Am J Med . 1987;83:1-9.Crossref 16. Balin PL, Tindall JP, Roenigk HH, Hogan MD. Is methotrexate therapy for psoriasis carcinogenic? a modified retrospective-prospective analysis. JAMA . 1975; 232:359-362.Crossref 17. Rustin GJS, Rustin F, Dent J, Booth M, Salt S. No increase in second tumors after cytotoxic chemotherapy for gestational trophoblastic tumors. N Engl J Med . 1982;308:473-476.Crossref 18. Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. J Rheumatol . 1985;12:S35-S39. 19. Lacher MJ. Spontaneous remission response to methotrexate in sarcoidosis. Ann Intern Med . 1968:69:1274-1278.Crossref 20. Fenton DA, Shaw M, Black MN. Invasive nasal sarcoidosis treated with methotrexate. Clin Exp Dermatol . 1985;10:279-283.Crossref 21. Israel HL The treatment of sarcoidosis. Postgrad Med J . 1970;46:537-540.Crossref 22. Tolman KG, Clegg DO, Lee RG, Ward JR. Methotrexate and the liver. J Rheumatol . 1985;12:S29-S34. 23. White DA, Rankin JA, Stover DE, Gellene RA, Gupta S. Methotrexate pneumonitis: bronchoalveolar lavage findings suggest an immunologie disorder. Am Rev Respir Dis . 1989;139:18-21.Crossref 24. Jones G, Mierins E, Karsh J. Methotrexate-induced asthma. Am Rev Respir Dis . 1991;143:179-181.Crossref 25. Mullarkey MF, Lammert JF, Blumenstein BA. Long-term methotrexate treatment in corticosteroid-dependent asthma. Ann Intern Med . 1990;112:577-581.Crossref 26. Lower EE, Smith JT, Martelo 0J, Baughman RP. The anemia of sarcoidosis. Sarcoidosis . 1988;5:51-55.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Apr 24, 1995

References