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Cyclosporine in the treatment of autoimmune disorders: a 10-year experience
Cyclosporine in the Treatment of Autoimmune Disorders: A 10-Year Experience D. Mitrovic, M. Popovic, B. Glisic, Lj. Pavlica, and M. Dimitrijevic
I
T HAS BEEN well established that cyclosporine (CyA) is efficacious in the prophylaxis and treatment of reactions leading to transplant rejection and in a large range of autoimmune and inflammatory disorders.1– 4 In the present study, we present our clinical experience in curing severe forms of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet’s disease (BD), and isolated vasculitis of the central nervous system (CNS vasculitis). The main criteria for selection of patients for CyA therapy were severity of illness and/or previous unsuccessful treatment. During the past 10 years, a total of 37 patients, aged between 20 and 67 years, 20 females and 17 males, were introduced to CyA therapy in the Clinic of Rheumatology and Clinical Immunology, MMA, Belgrade. Eighteen patients had BD (12 males and 6 females, mean age 34.3 years), 16 had RA (10 females, mean age 44.4 years and 6 males, mean age 52.5 years), 2 had severe SLE (2 females, mean age 34 years), and one patient had isolated CNS vasculitis (a 36-year-old woman). The severity of Behcet’s disease was characterized by ocular and CNS involvement. Chorioretinitis was detected in 7 of 18 patients, both chorioretinitis and uveitis anterior in 3 of 18 patients, only uveitis anterior in 3 of 18 patients, one patient had deep aphthous ulceration, and one patient had myocarditis. Patients with RA were in I-II anatomic and functional stage of the disease. All had previously been unsuccessfully treated with DMARDs (gold, antimalarials, depenicilamine, methotrexate, leflunomide). The duration of CyA treatment ranged from 15 days to 30 months, for all 37 patients. The daily dose of CyA was 3 to 5 mg/kg in patients with BD and SLE, 2.5 to 5 mg/kg in RA patients, while the patient with isolated CNS vasculitis received 5 mg/kg/d. According to the clinical, biochemical, and immunologic parameters, effects of the therapy were designated as “full” (complete clinical and biochemical remission), “partial” (clinical and/or biochemical improvement), and “lack of efficacy.” The full therapeutic response was achieved in 16 of 18 BD patients, 10 of 16 RA patients, as well as in patients with SLE and isolated CNS vasculitis (Fig 1). Treatment with CyA was not efficacious in two patients with BD, in one because of a short treatment period (15 days),
0041-1345/98/$19.00 PII S0041-1345(98)01369-4 4134
Fig 1. Response to CyA therapy in patients with BD, RA, SLE, and CNS vasculitis.
while the other patient developed gingival hypertrophy and discontinued treatment. In the RA group, one patient did not respond to CyA therapy, two developed arterial hypertension, and two had renal insufficiency. Therapy was interrupted in all. Partial therapeutic effect (incomplete regression of arthritis and partial improvement of biochemical signs of inflammation) was achieved in two RA patients (Fig 1). Taking into consideration the overall high rate of responders, CyA could be recommended in certain severe forms of autoimmune disease, particularly in Behcet’s disease, where it might be the drug of choice. REFERENCES 1. Masuda K, Nakajama A: In Schindler R (eds): Cyclosporine in Autoimmune Diseases. Berlin: Springer-Verlag; p 162, 1985 2. Mitrovic D, Popovic M, Pavlica Lj, et al: VSP 54:321, 1997 3. Cassava D, Lagana B, Mitterhofer AF, et al: Arthritis Rheum 40:27, 1997 4. Van den Borne BE, Landewer RB, Breedveld FC, et al: Scand J Rheumatol 25:307, 1996
From the Clinic of Rheumatology and Clinical Immunology, Military Medical Academy (D.M., M.P., B.G., L.P.), and Department of Microbiology and Immunology, University School of Pharmacy, (M.D.), Belgrade, Yugoslavia. Address reprint requests to Dr D. Mitrovic, Military Medical Academy, Clinic of Rheumatology and Clinical Immunology, Crnotravska 17, 11000 Belgrade, Yugoslavia.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 30, 4134 (1998)
I
T HAS BEEN well established that cyclosporine (CyA) is efficacious in the prophylaxis and treatment of reactions leading to transplant rejection and in a large range of autoimmune and inflammatory disorders.1– 4 In the present study, we present our clinical experience in curing severe forms of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet’s disease (BD), and isolated vasculitis of the central nervous system (CNS vasculitis). The main criteria for selection of patients for CyA therapy were severity of illness and/or previous unsuccessful treatment. During the past 10 years, a total of 37 patients, aged between 20 and 67 years, 20 females and 17 males, were introduced to CyA therapy in the Clinic of Rheumatology and Clinical Immunology, MMA, Belgrade. Eighteen patients had BD (12 males and 6 females, mean age 34.3 years), 16 had RA (10 females, mean age 44.4 years and 6 males, mean age 52.5 years), 2 had severe SLE (2 females, mean age 34 years), and one patient had isolated CNS vasculitis (a 36-year-old woman). The severity of Behcet’s disease was characterized by ocular and CNS involvement. Chorioretinitis was detected in 7 of 18 patients, both chorioretinitis and uveitis anterior in 3 of 18 patients, only uveitis anterior in 3 of 18 patients, one patient had deep aphthous ulceration, and one patient had myocarditis. Patients with RA were in I-II anatomic and functional stage of the disease. All had previously been unsuccessfully treated with DMARDs (gold, antimalarials, depenicilamine, methotrexate, leflunomide). The duration of CyA treatment ranged from 15 days to 30 months, for all 37 patients. The daily dose of CyA was 3 to 5 mg/kg in patients with BD and SLE, 2.5 to 5 mg/kg in RA patients, while the patient with isolated CNS vasculitis received 5 mg/kg/d. According to the clinical, biochemical, and immunologic parameters, effects of the therapy were designated as “full” (complete clinical and biochemical remission), “partial” (clinical and/or biochemical improvement), and “lack of efficacy.” The full therapeutic response was achieved in 16 of 18 BD patients, 10 of 16 RA patients, as well as in patients with SLE and isolated CNS vasculitis (Fig 1). Treatment with CyA was not efficacious in two patients with BD, in one because of a short treatment period (15 days),
0041-1345/98/$19.00 PII S0041-1345(98)01369-4 4134
Fig 1. Response to CyA therapy in patients with BD, RA, SLE, and CNS vasculitis.
while the other patient developed gingival hypertrophy and discontinued treatment. In the RA group, one patient did not respond to CyA therapy, two developed arterial hypertension, and two had renal insufficiency. Therapy was interrupted in all. Partial therapeutic effect (incomplete regression of arthritis and partial improvement of biochemical signs of inflammation) was achieved in two RA patients (Fig 1). Taking into consideration the overall high rate of responders, CyA could be recommended in certain severe forms of autoimmune disease, particularly in Behcet’s disease, where it might be the drug of choice. REFERENCES 1. Masuda K, Nakajama A: In Schindler R (eds): Cyclosporine in Autoimmune Diseases. Berlin: Springer-Verlag; p 162, 1985 2. Mitrovic D, Popovic M, Pavlica Lj, et al: VSP 54:321, 1997 3. Cassava D, Lagana B, Mitterhofer AF, et al: Arthritis Rheum 40:27, 1997 4. Van den Borne BE, Landewer RB, Breedveld FC, et al: Scand J Rheumatol 25:307, 1996
From the Clinic of Rheumatology and Clinical Immunology, Military Medical Academy (D.M., M.P., B.G., L.P.), and Department of Microbiology and Immunology, University School of Pharmacy, (M.D.), Belgrade, Yugoslavia. Address reprint requests to Dr D. Mitrovic, Military Medical Academy, Clinic of Rheumatology and Clinical Immunology, Crnotravska 17, 11000 Belgrade, Yugoslavia.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 30, 4134 (1998)