Efficacy of Methotrexate in Ankylosing Spondylitis: A Randomized, Double Blind, Placebo Controlled Trial

LAURA GONZALEZ-LOPEZ, ARACELI GARCIA-GONZALEZ, MONICA VAZQUEZ-DEL-MERCADO, JOSE F. MUÑOZ-VALLE, and JORGE I. GAMEZ-NAVA

ABSTRACT.

Objective. To evaluate the efficacy and safety of methotrexate (MTX) compared with placebo in patients with active ankylosing spondylitis (AS).

Methods. This 24 week, double bind, randomized, placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS. The primary outcome measure was a composite index of improvement in 5 of the following scales: severity of morning stiffness, physical well being, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and physician and patient global assessment of disease activity.

Results. Seventeen patients received MTX and 18 placebo. In the intention-to-treat analysis at 24 weeks, 53% of patients in the MTX group had a treatment response, compared with 17% in the placebo group (p = 0.03). We observed significant improvements with MTX in physical well being (p = 0.009), BASDAI (p = 0.02), BASFI (p = 0.02), physician global assessment (p < 0.001), patient global assessment (p = 0.03), and HAQ-S (p = 0.02). In the adjusted analysis only MTX determined the improvement in the primary outcome. At the end of the trial, one patient with MTX withdrew due to a lack of compliance, and one with placebo due to a lack of efficacy. We did not observe significant differences in rates of side effects between the 2 groups.

Conclusion. MTX is safe and effective for patients with AS. Longterm studies are needed to evaluate the permanence of its benefit. (J Rheumatol 2004;31:1568-74)

Key Indexing Terms:

ANKYLOSING SPONDYLITIS
METHOTREXATE
RANDOMIZED CONTROLLED TRIAL

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From the Department of Internal Medicine, Rheumatology, Hospital General Regional 110 del Instituto Mexicano del Seguro Social (IMSS); Section of Musculoskeletal Diseases and Autoimmunity, Clinical Epidemiology Research Unit, Hospital de Especialidades Centro Medico Nacional de Occidente IMSS; and the Molecular Biology Institute, Centro Universitario en Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, México.

Supported by the Fondo de Fomento a la Investigación del IMSS (grants FP 0038/824, FP 2001/150, and IMSS/2003-374).

L. Gonzalez-Lopez, MD, DSc, Department of Internal Medicine – Rheumatology, Hospital General Regional 110, IMSS, Guadalajara; A. Garcia-Gonzalez, MD, MSc; J.I. Gamez-Nava, MD, DSc, Research Associate, Section of Musculoskeletal Diseases and Autoimmunity, Clinical Epidemiology Research Unit, Hospital de Especialidades del Centro Medico Nacional de Occidente (HECMNO); M. Vazquez-Del Mercado, MD, PhD, Chair, Professor; J.F. Muñoz-Valle, BSc, PhD, Research Associate, Instituto de Biología Molecular en Medicina, CUCS, Universidad de Guadalajara.

Address reprint requests to Dr. L. Gonzalez-Lopez, Avenida Salto del Agua 2192, Jardines del Country, Guadalajara, Jalisco CP 44210, México. E-mail: lauragl@mail.udg.mx

Submitted August 12, 2003; revision accepted February 25, 2004.

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