Tratamento imunossupressor na esclerose múltipla

Oliveira, T. V.; Gorz-Reinhardt, A. M.; Gracia, C.m.; Bittencourt, P. R. M.

doi:10.1590/S0004-282X1992000300006

Resumos

Um estudo aberto, retrospectivo e não-controlado, foi realizado para avaliar a eficácia e tolerabilidade do tratamento imunossupressor instituído no período de 1982 a 1990 em pacientes com diagnóstico de esclerose múltipla clinicamente definida. Dos 42 pacientes, 18 (43%) foram tratados com uma só droga e 24 (57%) com mais de uma. A tolerabilidade foi avaliada após 6 meses de tratamento em 42 pacientes, dos quais 6 receberiam tratamento com prednisona, 26 com azatioprina, 17 com metilprednisolona e 15 com pulsos de ciclofosfa-mida. Ocorreram efeitos colaterais reversíveis, de intensidade leve a moderada, em 54% dos pacientes em uso de azatioprina, sendo necessário diminuir a dose ou suspender definitivamente a medicação. Foram observados efeitos adversos em 40% dos pacientes em uso de pulsos de ciclofosfamida e em 12% dos pacientes em tratamento com pulsos de metilprednisolona. Efeitos colaterais relacionados ao uso crônico dos corticóides ocorreram em 83% dos pacientes. Avaliação da eficácia após 2 anos de tratamento imunossupressor, em 15 pacientes com seguimento adequado, mostrou aparente parada do progresso da doença, sugerindo benefício da imunossu-pressão em casos com evolução rápida e inabilidade crescente.

esclerose múltipla; terapêutica; drogas imunossupressoras

An open, retrospective, uncontrolled study was carried out to evaluate efficacy and tolerability of immunesuppressive therapy used in the period 1982-1990 in patients with clinically definite multiple sclerosis. Of 42 patients 43% were treated with one drug, and the others with more than one. Tolerability was evaluated after at least 6 months of therapy in 6 patients on prednisone, 28 on azathioprine, 17 on methyl-prednisolone and 15 on cyclophosphamide pulses. Reversible mild or moderate side-effects were noted in 54% of the patients on azathioprine, heading to change in dose or withdrawal. There were similar side-effects in 83% of the patients on prednisone, 40% of those on cyclophosphamide, and in 12% of those on methylprednisolone. Efficacy was evaluated in 15 patients with a follow-up of at least 2 years, measured by objective scales. The results indicated therapy appeared to arrest progress of disability. We conclude that this study supports the use of immunesuppresssion in selected cases with rapidly evolving neurological deficits.

multiple sclerosis; therapeutics; immunesuppressive drugs

T. V. Oliveira^I; A. M. Gorz-Reinhardt^I; C.m. Gracia^I; P. R. M. Bittencourt^II

^INeurologista. Unidade de Neurologia Clínica dos Hospitais Nossa Senhora das Graças e Santa Cruz, Centro Diagnóstico de Curitiba e Centro Dia - Clínica de Recuperação, Curitiba

^IINeurologista, Chefe da Unidade. Unidade de Neurologia Clínica dos Hospitais Nossa Senhora das Graças e Santa Cruz, Centro Diagnóstico de Curitiba e Centro Dia - Clínica de Recuperação, Curitiba

RESUMO

Um estudo aberto, retrospectivo e não-controlado, foi realizado para avaliar a eficácia e tolerabilidade do tratamento imunossupressor instituído no período de 1982 a 1990 em pacientes com diagnóstico de esclerose múltipla clinicamente definida. Dos 42 pacientes, 18 (43%) foram tratados com uma só droga e 24 (57%) com mais de uma. A tolerabilidade foi avaliada após 6 meses de tratamento em 42 pacientes, dos quais 6 receberiam tratamento com prednisona, 26 com azatioprina, 17 com metilprednisolona e 15 com pulsos de ciclofosfa-mida. Ocorreram efeitos colaterais reversíveis, de intensidade leve a moderada, em 54% dos pacientes em uso de azatioprina, sendo necessário diminuir a dose ou suspender definitivamente a medicação. Foram observados efeitos adversos em 40% dos pacientes em uso de pulsos de ciclofosfamida e em 12% dos pacientes em tratamento com pulsos de metilprednisolona. Efeitos colaterais relacionados ao uso crônico dos corticóides ocorreram em 83% dos pacientes. Avaliação da eficácia após 2 anos de tratamento imunossupressor, em 15 pacientes com seguimento adequado, mostrou aparente parada do progresso da doença, sugerindo benefício da imunossu-pressão em casos com evolução rápida e inabilidade crescente.

Palavras-chave: esclerose múltipla, terapêutica, drogas imunossupressoras.

SUMMARY

An open, retrospective, uncontrolled study was carried out to evaluate efficacy and tolerability of immunesuppressive therapy used in the period 1982-1990 in patients with clinically definite multiple sclerosis. Of 42 patients 43% were treated with one drug, and the others with more than one. Tolerability was evaluated after at least 6 months of therapy in 6 patients on prednisone, 28 on azathioprine, 17 on methyl-prednisolone and 15 on cyclophosphamide pulses. Reversible mild or moderate side-effects were noted in 54% of the patients on azathioprine, heading to change in dose or withdrawal. There were similar side-effects in 83% of the patients on prednisone, 40% of those on cyclophosphamide, and in 12% of those on methylprednisolone. Efficacy was evaluated in 15 patients with a follow-up of at least 2 years, measured by objective scales. The results indicated therapy appeared to arrest progress of disability. We conclude that this study supports the use of immunesuppresssion in selected cases with rapidly evolving neurological deficits.

Key words: multiple sclerosis, therapeutics, immunesuppressive drugs.

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Agradecimentos Os autores reconhecem o apoio da comunidade médica do Paraná e Santa Catarina, bem como do Corpo Clínico do Hospital Nossa Senhora das Graças, em especial da equipe de Neurocirurgia (Serviço do Prof. Affonso Antoniuk), por referir pacientes para o tratamento imunossupressor. Agradecemos ainda à Marli Osna pela boa-vontade no processamento de palavras.

Dra. Teresinha Valente de Oliveira Unidade de Neurologia Clínica, Hospital Nossa Senhora das Graças - Rua Alcides Munhoz 433 - 80510 Curitiba PR - Brasil.

1. Amato MP, Siracusa AG, Fratiglioni, L, Amaducci L. Azathioprine therapy and cancer risk in multiple sclerosis: a prospective long-term study. Ann Neurol 1990, 28:255-282.
2. Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V, Weiss W, Arnon R, Jacobsohn I, Teitel-baum D, Sela M. A pilot trial of cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 1987, 317:408-414.
3. Durelli L, Cocito D, Riccio A, Barile C, Bergamasco B, Baggio GF, Perla F, Delsedime M, Gusmaroli G, Bergamini L. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology 1986, 36:238-243.
4. Gooukin de, Plencner S, Palmer-Saxerud J, Teetzen M, Hertsgaard D. Cyciophospha-mide in chronic progressive multiple sclerosis. Maintenance vs nonmaintenance therapy. Arch Neurol 1987, 44:823-827.
5. Killian JM, Bressler RB, Armstrong RM, Huston DP. Controlled pilot trial of monthly intravenous cyclophosphamide in multiple sclerosis. Arch Neurol 1988, 45:27-30.
6. Kurtzke JF. Neurological impairment in multiple sclerosis and the disability status scale. Acta Neurol Scand 1970, 46:493-512.
7. Kurtzke JF. A proposal for a uniform minimal record of disability in multiple sclerosis Acta Neurol Scand 1981, 64:110-129.
8. Lyons PR, Newman PK, Saunders M. Methylprednisolone therapy in multiple sclerosis, a profile of adverse effects. J Neurol Neurosurg Psychiatry 1988, 51:285-287.
9. Milligan NM, Newcombe R, Compston DAS. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: clinical effects. J Neuroi Neurosurg Psychiatry 1987, 50:511-516.
10. Myers LW, Fahey JL, Moody DJ, Mickey MR, Frane MV, Ellison GW. Cyclophospha mide pulses in chronic progressive multiple sclerosis: a preliminary clinical trial. Arch Neurol 1987, 44:828-832.
11. Oliveira TV, Carvalho RM, Seixas RR, Gorz AM, Bittencourt PRM. Esclerose múltipla: critérios objetivos de diagnóstico. Arq Neuro-Psiquiat (São Paulo), 1991, 49:33-42.
12. Hotz PH, Klippel JH, Decker JL, Grauman D, Wolff B, Brown BC, Rutt G. Bladder complications in patients receiving cyclophosphamide lor systemic lupus erythematosus or rneumatoid arthritis. Ann Intern Med 1979, 91:221-223.
13. Poser CM, Paty DW, Scheinberg L, MacDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberbergh DH, Tourtellotte WW. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983, 13:227-231.
14. Rudge P, Koetsier JC, Mertin J, Mispeblom Beyer JO, Vanwalbeek HK, Clifford Jones R, Harrison J, Robinson ,K, Medlein B, Poole T Stokvis JCJM, Timonen P. Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry 1989, 52:559-565.
15. Steck AJ, Regli F, Ochsner F, Gauthier G. Cyclosporine versus azathioprine in the treatment of multiple sclerosis: 12-month clinical and immunological evaluation. Eur Neurol 1990, 30:224-228.
16. Steinberg AD. Cyclophosphamide: should it be used daily, monthly, or never? N Engl J Med 1984, 16:458-459.
17. The Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinicai trial. Ann Neurol 1990, 27:591-605.
18. Troiano R, Cook SD, Dowling PC. Steroid therapy in multiple slcerosis: point of view. Arch Neurol 1987, 44:803-807.
19. Weiner HL, Hafler DA. Immunotherapy of multiple sclerosis. Ann Neurol 1988, 23:211-222.
20. Weinshenker BG, Bass B, Rice GPA, Noseworthy J, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study I. Clinical Course and disability. Brain 1989, 112:133-146.

Tratamento imunossupressor na esclerose múltipla

Immunosuppressive treatment in multiple sclerosis

Datas de Publicação

Publicação nesta coleção
22 Fev 2011
Data do Fascículo
Set 1992

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Amato MP, Siracusa AG, Fratiglioni, L, Amaducci L. Azathioprine therapy and cancer risk in multiple sclerosis: a prospective long-term study. Ann Neurol 1990, 28:255-282.

[2] 2. Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V, Weiss W, Arnon R, Jacobsohn I, Teitel-baum D, Sela M. A pilot trial of cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 1987, 317:408-414.

[3] 3. Durelli L, Cocito D, Riccio A, Barile C, Bergamasco B, Baggio GF, Perla F, Delsedime M, Gusmaroli G, Bergamini L. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology 1986, 36:238-243.

[4] 4. Gooukin de, Plencner S, Palmer-Saxerud J, Teetzen M, Hertsgaard D. Cyciophospha-mide in chronic progressive multiple sclerosis. Maintenance vs nonmaintenance therapy. Arch Neurol 1987, 44:823-827.

[5] 5. Killian JM, Bressler RB, Armstrong RM, Huston DP. Controlled pilot trial of monthly intravenous cyclophosphamide in multiple sclerosis. Arch Neurol 1988, 45:27-30.

[6] 6. Kurtzke JF. Neurological impairment in multiple sclerosis and the disability status scale. Acta Neurol Scand 1970, 46:493-512.

[7] 7. Kurtzke JF. A proposal for a uniform minimal record of disability in multiple sclerosis Acta Neurol Scand 1981, 64:110-129.

[8] 8. Lyons PR, Newman PK, Saunders M. Methylprednisolone therapy in multiple sclerosis, a profile of adverse effects. J Neurol Neurosurg Psychiatry 1988, 51:285-287.

[9] 9. Milligan NM, Newcombe R, Compston DAS. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: clinical effects. J Neuroi Neurosurg Psychiatry 1987, 50:511-516.

[10] 10. Myers LW, Fahey JL, Moody DJ, Mickey MR, Frane MV, Ellison GW. Cyclophospha mide pulses in chronic progressive multiple sclerosis: a preliminary clinical trial. Arch Neurol 1987, 44:828-832.

[11] 11. Oliveira TV, Carvalho RM, Seixas RR, Gorz AM, Bittencourt PRM. Esclerose múltipla: critérios objetivos de diagnóstico. Arq Neuro-Psiquiat (São Paulo), 1991, 49:33-42.

[12] 12. Hotz PH, Klippel JH, Decker JL, Grauman D, Wolff B, Brown BC, Rutt G. Bladder complications in patients receiving cyclophosphamide lor systemic lupus erythematosus or rneumatoid arthritis. Ann Intern Med 1979, 91:221-223.

[13] 13. Poser CM, Paty DW, Scheinberg L, MacDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberbergh DH, Tourtellotte WW. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983, 13:227-231.

[14] 14. Rudge P, Koetsier JC, Mertin J, Mispeblom Beyer JO, Vanwalbeek HK, Clifford Jones R, Harrison J, Robinson ,K, Medlein B, Poole T Stokvis JCJM, Timonen P. Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry 1989, 52:559-565.

[15] 15. Steck AJ, Regli F, Ochsner F, Gauthier G. Cyclosporine versus azathioprine in the treatment of multiple sclerosis: 12-month clinical and immunological evaluation. Eur Neurol 1990, 30:224-228.

[16] 16. Steinberg AD. Cyclophosphamide: should it be used daily, monthly, or never? N Engl J Med 1984, 16:458-459.

[17] 17. The Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinicai trial. Ann Neurol 1990, 27:591-605.

[18] 18. Troiano R, Cook SD, Dowling PC. Steroid therapy in multiple slcerosis: point of view. Arch Neurol 1987, 44:803-807.

[19] 19. Weiner HL, Hafler DA. Immunotherapy of multiple sclerosis. Ann Neurol 1988, 23:211-222.

[20] 20. Weinshenker BG, Bass B, Rice GPA, Noseworthy J, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study I. Clinical Course and disability. Brain 1989, 112:133-146.