[Interferon-alpha2b recombinant improved the cognitive dysfunction in patients with relapsing remitting multiple sclerosis]. / El interferón-alpha2b recombinante mejora la disfunción cognitiva en pacientes con esclerosis múltiple.

INTRODUCTION: Some experimental, Phase II clinical trials and the preliminary reports of the Cuban Phase III clinical trial indicate that alpha-IFN (IFN) may be useful in relapsing remitting (RR) multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive dysfunction. OBJECTIVE: To assess the efficacy of IFN-alpha2b recombinant in the cognitive dysfunction of RR MS. PATIENTS AND METHODS: 57 RR-MS clinical definite patients from the randomised, double blind, placebo controlled study of 225 patients with RR-MS and brain MRI confirmed. Patients were randomly assigned to receive intramuscular IFN-alpha2b (Heberon R) 10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton and PASAT-3. Adverse events and side effects were not evaluated to maintain physician blinding. RESULTS: The initial comparison of the groups did not show any differences among the placebo (n=20), low dose (n=18) and high dose (n=19) considering age (p=0.234), gender, ethnic group (p=0.012), years ill (p=0.787), EDSS (p=0.203) and rate of relapses (p=0.432). The Luria's Test showed an improved in the low dose group from 2.50 +/- 1.34 to 1.39 +/- 1.85 (p=0.029) and in the high dose group from 3.22 +/- 1.89 to 2.17 +/- 1.50 (p=0.006) vs placebo 2.85 +/- 1.66 to 2.90 +/- 1.97 (p=0.723). The results of the Benton's test demonstrated that the low dose group had an improved from 5.50 +/- 1.10 to 6.22 +/- 1.31 (p=0.047), in the high dose group from 4.87 +/- 1.85 to 5.78 +/- 1.35 (p=0.005) where as in the placebo group worse from 5.15 +/- 1.76 to 5.05 +/- 2.11 (p=0.893). The WAIS test showed the same results, the low dose group increased from 5.17 +/- 1.34 to 6.06 +/- 1.21 (p=0.022), the high dose group from 4.56 +/- 1.38 to 5.39 +/- 1.29 (p=0.007) and the placebo group worse from 5.25 +/- 1.25 to 5.05 +/- 1.57 (p=0.354). Finally, the PASAT-3 test increased in the IFNs groups: from 45.72 +/- 10.61 to 49.94 +/- 11.68 (p=0.015) in the low dose group, from 42.67 +/- 11.04 to 48.72 +/- 8.84 (p=0.03) in the high dose group, but in the placebo group worse from 44.55 +/- 10.86 to 41.95 +/- 13.74 (p=0.655). CONCLUSION: IFN-alpha improved the cognitive dysfunction in RR-MS patients. The higher dose is more beneficial.

El interferón alfa-2b recombinante mejora la disfunción cognitiva en pacientes con esclerosis múltiple / Interferon alpha-2b recombinant improved the cognitive dysfunction in patients with relapsing-remitting multiple sclerosis

Introducción. Ensayos clínicos recientes indican que el interferón (IFN)alfa-2b recombinante, parece ser útil en la forma exacerbación-remisión (ER) de la esclerosis múltiple (EM). Un 70 por ciento los pacientes con EM en Cuba tienen disfunción cognitiva. Objetivo. Evaluar la eficacia del IFNa2b en los trastornos cognitivos de la EM. Pacientes y métodos. 57 pacientes con EM-ER clínicamente definida y confirmada por RM, del ensayo clínico en Cuba, fase III, multicentro, aleatorizado, doblemente ciego y controlado con placebo. Los pacientes se distribuyeron en: grupo I, con 10 millones (MI) de UI de IFNalf-a2b (Heberon-R ®) intramuscular; el grupo II, con 3 MI IFNalfa-2b y grupo III,con placebo, dos veces a la semana, durante dos años. Las evaluaciones fueron a ciegas, al inicio y al final, mediante la escala neuropsicológica de Luria, Benton visual retention test, escala verbal WAISR ( Weschler adult intelligence-revised) y el PASAT-3 (paced auditory serial addition test). La detección de anticuerpos neutralizantes (ACN) al IFNalfa-2b, se realizó semestralmente. Resultados. Los resultados iniciales no demostraron diferencias significativas entre los grupos para las variables demográficas, clínicas y de discapacidad. Los resultados del Luria fueron: placebo [inicial (I)/final (F)] 2,85 ñ 1,66/2,90 ñ 1,97 (p = 0,723); IFNalfa-2b 3 MI (I/F): 2,50 ñ 1,34/1,39 ñ 1,85 (p = 0,029); IFNalfa-2b 10 MI (I/F): 3,22 ñ 1,69/2,17 ñ 1,50 (p = 0,006). Al fusionar los dos grupos IFNa2b frente a placebo se obtuvo p = 0,021 frente a 0,367. En el Benton, los resultados fueron: placebo (I/F): 5,15 ñ 1,76/5,05 ñ 2,11 (p = 0,893); IFNalfa-2b 3 MI (I/F): 5,50 ñ 1,10/6,22 ñ 1,31 ( p = 0,047); IFNalfa-2b 10 MI (I/F): 4,67 ñ 1,85/5,78 ñ 1,35 (p = 0,005). Al unir los grupos IFNalfa-2b frente a placebo, se obtuvo p = 0,181 frente a 0,440. En el test WAIS se encontró: placebo (I/F): 5,25 ñ 1,25/5,05 ñ 1,57 (p = 0,354); IFNalfa-2b 3 MI (I/F): 5,17 ñ 1,34/6,06 ñ 1,21 ( p = 0,022); IFNalfa-2b 10 MI (I/F): 4,56 ñ 1,38/5,39ñ1,29 (p = 0,007). Al comparar los grupos IFNalfa-2b frente a placebo (I/F) se obtuvo p = 0,026 frente a 0,216. Los resultados del PASAT-3 fueron: placebo (I/F): 44,55 ñ 10,86/41,95 ñ 13,74 (p = 0,655); IFNa2b 3 MI (I/F), 45,72 ñ 10,61/49,94 ñ 11,68 ( p = 0,015); IFNalfa-2b 10 MI (I/F), 42,67 ñ 11,04/48,72 ñ 8,84 (p = 0,003). Al comparar los grupos IFN frente a placebo, con el PASAT-3, se obtuvo p = 0,033 frente a 0,621. Los ACN contra el IFNalfa-2b se detectaron en un 3,5 por ciento de los casos. Conclusiones. El IFNa2b mejora las alteraciones cognitivas en la EM-ER. Esta mejoría es dependiente de la dosis y la frecuencia de ACN es muy baja (AU)

Introduction. Some experimental, Phase II clinical trials and the preliminary reports of the Cuban Phase III clinical trial indicate that alpha-IFN (IFN) may be useful in relapsing-remitting (RR) multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive dysfunction. Objective. To assess the efficacy of IFN-alpha 2b recombinant in the cognitive dysfunction of RR-MS. Patients and methods. 57 RR-MS clinical definite (Poser et al) patients from the randomised, double-blind, placebo-controlled study of 225 patients with RR-MS and brain MRI confirmed. Patients were randomly assigned to receive intramuscular IFN alpha-2b (Heberon-R ®) 10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton and PASAT-3. Adverse events and side effects were not evaluated to maintain physician blinding. Results. The initial comparison of the groups did not show any differences among the placebo (n= 20), low dose (n= 18) and high dose (n= 19) considering age (p= 0.234), gender, ethnic group (p= 0.012), years ill (p= 0.787), EDSS (p=0.203) and rate of relapses (p= 0.432).The Luria’s Test showed an improved in the low dose group from 2.50±1.34 to 1.39±1.85 (p= 0.029) and in the high dose group from 3.22±1.89 to 2.17±1.50 (p= 0.006) vs placebo 2.85±1.66 to 2.90±1.97 (p=0.723). The results of the Benton’s test demonstrated that the low dose group had an improved from 5.50±1.10 to 6.22±1.31 (p= 0.047), in the high dose group from 4.87±1.85 to 5.78±1.35 (p= 0.005) where as in the placebo group worse from 5.15±1.76 to 5.05±2.11 (p= 0.893). The WAIS test showed the same results, the low dose group increased from 5.17±1.34 to 6.06±1.21 (p= 0.022), the high dose group from 4.56±1.38 to 5.39±1.29 (p= 0.007) and the placebo group worse from 5.25±1.25 to 5.05±1.57 (p=0.354). Finally, the PASAT-3 test increased in the IFNs groups: from 45.72±10.61 to 49.94±11.68 (p= 0.015) in the low dose group, from 42.67±11.04 to 48.72±8.84 (p= 0.03) in the high dose group, but in the placebo group worse from 44.55±10.86 to 41.95±13.74 (p= 0.655). Conclusion. IFN alpha improved the cognitive dysfunction in RR-MS patients. The higher dose is more beneficial (AU)