Clinical use of immunosuppressive drugs: part II

Abstract

In haematological diseases, insufficient data has been accumulated to evaluate the efficacy of immunosuppressive drug treatment in patients with erythroid aplasia or sideroblastic anaemia. Cyclophosphamide may be efficacious in inhibiting circulating anticoagulants in patients who need continued replacement of clotting factors. Azathioprine, 6-mercaptopurine, cyclophosphamide and vincristine have been used successfully in treating patients with idiopathic thrombocytopenic purpura, and some patients with auto-immune haemolytic anaemia may benefit from the addition of purine analogues. However, the use of immunosuppressive therapy seems to accelerate the presence of haematological malignancies in patients with macroglobulinaemia. In gastro-intestinal diseases, uncontrolled studies have shown nitrogen mustard, 6-mercaptopurine and azathioprine to be of modest benefit to patients with ulcerative colitis and Crohn's disease. In a controlled trial azathioprine plus prednisone proved more effective than prednisone alone in sustaining remission in patients with Crohn's disease. In patients with either chronic active hepatitis or primary biliary cirrhosis, however, there seems to be no benefit from immunosuppressive therapy for primary treatment of these diseases. Cyclophosphamide, azathioprine and methotrexate have all been used with some success in treating patient with uveitis, and in a controlled trial cytarabine has been shown to be beneficial to patients with herpes ophthalmicus. However, no benefit has been shown to patients with the eye changes of Graves' disease with either azathioprine or methotrexate. Patients with Paget's disease appear to be helped by mithramycin. Cyclophosphamide, chlorambucil and azathioprine are ineffective in treating patients with multiple sclerosis. 6-Mercaptopurine, azathioprine, methotrexate and cyclophosphamide have all produced some benefit in patients with myasthenia gravis, and some patients with idiopathic pulmonary haemosiderosis have responded to azathioprine, 6-mercaptopurine and cyclophosphamide. Alkylating agents have proved useful in treating some patients with asthma and in treating frequent relapsers among children with the nephrotic syndrome. In adults with membrano-proliferative glomerulonephritis some patients have responded to combination therapy with cyclophosphamide, azathioprine and corticosteroids. Immunosuppressive therapy is also indicated in prolonging graft survivals in patients receiving organ transplants. Drug toxicities of immunosuppressive agents are discussed. Their long-term effects, including mutagenic potential, have as yet not been fully elucidated.