Hotline Archive - Lymphoproliferative Disease in Patients with Autoimmune Disease on Low-Dose Methotrexate
June 1995
Lederle Laboratories sent a letter to physicians on April 24, 1995, updating them on the possible adverse effects of low-dose methotrexate in patients with autoimmune disease. Of special interest was the discussion of lymphoproliferative disorders in which nine cases were noted in seven reports over the last several years. Eight cases occurred in patients with rheumatoid arthritis and one case in a patient with dermatomyositis. Of these cases, four regressed spontaneously after cessation of methotrexate suggesting a causal relationship. One was a Hodgkin's lymphoma, one was a non-Hodgkin's lymphoma, and two were undefined lymphoproliferative disorders. Five other patients had non-Hodgkin's lymphoma. None had Sjogren's syndrome. Four received cytotoxic therapy, and two died of disseminated disease. Complete disappearance of lymphomas and lymphoproliferative disease has been documented in organ transplant patients when immunosuppressive therapy was withdrawn. Some studies have shown an increased frequency of hematologic malignancies, especially non-Hodgkin's lymphoma in patients with rheumatoid arthritis and other autoimmune diseases. This could reflect altered immune function associated with the disease or disease-modifying drug therapy.
Non-Hodgkin's lymphoma and other lymphomas may appear rarely in patients receiving low-dose methotrexate therapy. Some of these lymphoproliferative disorders may spontaneously regress when the methotrexate is withdrawn and not require cytotoxic therapy. There are no controlled human studies evaluating the risk of neoplasia with methotrexate, and animal studies are inconclusive. Controlled trials and observational studies have shown low-dose methotrexate to be a second line agent of high potency with a favorable profile of safety in patients with rheumatoid arthritis. Methotrexate is the drug with the highest long-term continuation rate in rheumatoid arthritis patients. Other life-threatening events such as severe hemocytopenia and methotrexate pneumonitis are rare and amendable to recognizing risk factors and promonitory signs.
These reports, while interesting, should not be overemphasized in their importance. Physicians prescribing methotrexate should be aware of the small number of lymphomas reported despite the widespread use of this drug.
Prepared by Robert Thoburn, MD, and Paul Katz, MD
Co-Editors, ACR Hotline
June 1,1995
This Hotline is provided by the American College of Rheumatology Communications and Marketing Group as an informational service for members. This Hotline does not represent a position statement of the College.
