Effectiveness and safety of the treatment of lysosomal deposit diseases: Analysis of 22 patients

Abstract

Objectives

Identify the efficacy variables collected in the literature for therapies used in lysosomal storage diseases (LDS), evaluate the quality of this evidence, and know the effectiveness and safety of these treatments.

Material and methods

Retrospective observational study that included patients with LDS treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Published clinical trials (CT) and LDS treatment guidelines were reviewed to select efficacy variables. Data to measure them (and adverse effects) were obtained from the medical history.

Results

No CTs have been found in which efficacy is evaluated with final variables, all have been surrogated. Twenty-two patients were included: eight with Gaucher disease, six with Niemann-PickC disease, two with Hunter disease, one with Morquio-A disease, and five with Pompe disease. Eight patients have responded to ERT and one to SRT with eliglustat. ERT hasn't been associated with adverse effects. Miglustat has produced tolerance problems, requiring a change in a patient.

Conclusions

The effectiveness was variable according to the pathology. Regarding safety, manageable adverse reactions to SRT were associated with dosage adjustments.

Resumen

Objetivos

Los objetivos son: identificar variables de eficacia empleadas en fármacos para enfermedades de depósito lisosomal (EDL), evaluar la calidad de esta evidencia, y conocer la efectividad y seguridad de estos tratamientos.

Material y metodos

Estudio observacional retrospectivo que incluyó pacientes con EDL tratados con terapia de sustitución enzimática (TSE) o de reducción de sustrato (TRS). Se revisaron los ensayos clínicos (EC) publicados y guías de tratamiento de EDL para seleccionar variables de eficacia. Se obtuvieron los datos para medirlas (y efectos adversos) de la historia clínica.

Resultados

No se encontraron EC en los que se evalúe eficacia con variables finales, todas fueron subrogadas. Se incluyeron 22 pacientes: ocho con enfermedad de Gaucher, seis con enfermedad de Niemann-PickC, dos con enfermedad de Hunter, uno con enfermedad de Morquio-A y cinco con enfermedad de Pompe. Ocho pacientes respondieron a TSE y uno a TRS. La TSE no se relacionó con efectos adversos. Miglustat produjo problemas de tolerancia que requirieron cambio de tratamiento en un paciente.

Conclusiones

La efectividad fue variable según la patología. Respecto a seguridad, se asociaron reacciones adversas a TRS manejables con ajustes posológicos.