Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study.
Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis (SPMS) who do not respond to interferon beta (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone. Patients with SPMS were eligible for this non-controlled prospective study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the year preceeding the study. Patients were to continue treatment with IFNB-1b (8 MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in terms of adverse reactions and laboratory measures graded according to the WHO toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI) results. Neutralizing antibodies (NAB) were measured. Ten SPMS patients (6 females) with a median EDSS score of 4.5 were enrolled. One patient withdrew because of gastrointestinal complaints, one was withdrawn owing to poor compliance, and 8 patients completed therapy. The only frequent side effect was lymphopenia, reported at least once in all patients. Annual relapse rate was reduced by approximately 50 % in the second year. There was a significant trend for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24 months; only one patient had active lesions. No changes were seen in the 9-HPT. There was a significant improvement in neuropsychological tests after 24 months ( p = 0.045). One patient tested positive for NAB throughout the study, and transient NAB were detected in 4 patients. In conclusion, combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS. Strict clinical and laboratory monitoring is recommended during this combination therapy.
Servicio de Neurología, Complejo Hospitalario Carlos Haya Avda, Carlos Haya, 29010 Málaga, Spain. ofernand@hch.sas.cica.es
Oscar
O
Fernández
Miguel
M
Guerrero
Cristobalina
C
Mayorga
Luis
L
Muñoz
Antonio
A
Leán
Gloria
G
Luque
Miguel
M
Hervás
Victoria
V
Fernández
Antonio
A
Capdevila
Enrique
E
de Ramón
D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects* / Q000627:therapeutic use; D008231:Lymphopenia / Q000139:chemically induced*; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D000068576:Interferon beta-1b; D016899:Interferon-beta; D001379:Azathioprine; D000068556:Interferon beta-1a