ABORDAJE TERAPÉUTICO
EN LAS
ENFERMEDADES AUTOINMUNES SISTÉMICAS
Pautas de tratamiento
en las formas severas
Parte 2
Dr. Lucio Pallarés Ferreres
Unitat Malalties Autoimmunes Sistèmiques
Servicio de Medicina Interna
Hospital Universitario Son Dureta
“GOLD STANDARD” en el Tratamiento
Actualmente:
• Diversas pautas de administración en fase de inducción
• Nuevos Fármacos Inmunodepresores
CORTICOIDES: Pauta de Administración
BOLUS de Metilprednilsona (EV)
• (Solu-Moderín®) 1 gramo, en 500ml de suero salino
• Administrar en 4-6 horas
• Puede repetirse diariamente durante 3-4 días
CORTICOIDES: Pauta de Administración
BOLUS de Metilprednilsona (EV)
• Posteriormente, puede seguirse el tratamiento con dosis de
corticoides de 0,5mg/Kg. de peso/día.
• Aunque de forma infrecuente, la administración en bolus de
corticoides puede ocasionar problemas cardiovasculares, con
aparición de arritmias.
CICLOFOSFAMIDA: Pauta de Administración
BOLUS de Ciclofosfamida (EV)
• (Genoxal®) 0,750 gramos/m2, en 250ml de suero salino
• Administrar en 60-90 minutos
• Mantener hidratación (2000-3000 ml suero glucosalino)
• Asociar antiemético: ondansetrón (Zofrán®) 1 ampolla/EV
antes del Bolus. Puede repetirse a las 4h y a las 8h post-bolus
• Periodicidad Mensual
CICLOFOSFAMIDA: Pauta de Administración
BOLUS de Ciclofosfamida (EV) Ajuste dosis mensuales
• Cada 15 días post-Bolus: Control hematológico
<3000 leuc.
0,500 gr./m2
3000-5000 leuc.
0,750 gr./m2
>5000 leuc.
1,000 gr./m2
CICLOFOSFAMIDA: Pauta “Clásica”
ALTAS DOSIS A LARGO PLAZO
• Bolus MENSUAL, durante 6 meses (puede prorrogarse)
• Posteriormente Bolus TRIMESTRAL durante 1-2 años
• Posteriormente cambiar de Inmunodepresor (Azatioprina)
CICLOFOSFAMIDA: Pauta “Corta”
ALTAS DOSIS A CORTO PLAZO
• Bolus MENSUAL, máximo 6 meses
• Posteriormente cambiar de Inmunodepresor (Azatioprina)
CICLOFOSFAMIDA: Pauta “Bajas Dosis”
BAJAS DOSIS (Pauta St. Thomas’ Hospital)
• (Genoxal®) 0,500 gramos en 250ml de suero salino
• Periodicidad QUINCENAL, durante 3 meses (6 Bolus)
• Posteriormente cambiar de Inmunodepresor (Azatioprina)
Annals of the Rheumatic Diseases
Volume 56, Number 8 (August 1, 1997)
Immunosuppressive treatment in severe connective tissue
diseases: effects of low dose intravenous cyclophosphamide
Martin-SuarezA1, M. MansoorA2, A.P. FernandesA3, M.A. KhamashtaA4, G.R.V. HughesA5, D.
D'CruzA6
Immunosuppressive treatment in severe connective tissue
diseases: effects of low dose intravenous cyclophosphamide
Objective
To review our experience with low dose intravenous pulse
cyclophosphamide in the treatment of patients with severe
connective tissue diseases.
Patients
Ninety patients with severe connective tissue diseases: systemic
lupus erythematosus (SLE) (n=43); systemic vasculitides (n=42);
idiopathic inflammatory myopathies (n=4); mixed essential
cryoglobulinaemic vasculitis (n=1). Median age was 48 (22-76)
years with a median disease duration of 94 (18-250) months.
Immunosuppressive treatment in severe connective tissue
diseases: effects of low dose intravenous cyclophosphamide
Results
Complete or partial remission was noted in 75.5% after a median
follow up of 56 (5-213) months. Vasculitis, Churg-Strauss syndrome,
Wegener's granulomatosis, and neuropsychiatric lupus showed the
best initial response but 58% of Wegener's patients relapsed.
Median corticosteroid doses were significantly reduced.
Adverse events: infections (7), neutropenia (5), lymphopenia (18),
and haemorrhagic cystitis (3). None of the women had prolonged
amenorrhoea. Five patients doubled their serum creatinine and five
died from sepsis (2) or severe disease (3).
Immunosuppressive treatment in severe connective tissue
diseases: effects of low dose intravenous cyclophosphamide
Conclusion
Treatment of severe connective tissue diseases with 'low dose'
intravenous cyclophosphamide pulses compares in efficacy with the
higher monthly doses previously advocated. Treatment was well
tolerated with fewer adverse effects and most significantly, there were
no cases of premature ovarian failure.
Ninety patients with lupus nephritis were treated with three pulses
of intravenous methylprednisolone (IV MP) after which they were
allocated to one of two groups
The high-dose group received IV CYC 0.5 g/m2 every month for 6
months, increased according to the nadir white cell count. These
patients then received two further pulses of IV CYC.
The low-dose group received 500 mg IV CYC every 2 weeks for a
total of six infusions. Both groups were given azathioprine (2
mg/kg/day) after remission was induced.
Follow-up in this study was for a median of 41 months.
Results:
Renal remission was seen in 71% of patients in the low-dose group
and 54% in the high-dose CYC group. This difference was not
statistically significant. Treatment failures in both groups was similar
(16%). The ELNT confirms that low-dose IV CYC demonstrates a
comparable efficacy to a high-dose treatment regime.
There was more infections with high-dose CYC, with twice as many
infections occurring in this group.
Low incidence of amenorrhoea in the high-dose group (cumulative
dose of CYC was lower than in the standard NIH regime).
The alternative low-dose regime has not been supported
by sufficiently long or sufficiently numerous trials to be
accepted as an adequate replacement for the NIH
platinum standard regime.
Further large trials comparing the high-dose and lowdose CYC regimes will be carried out