OBJECTIVES: To analyse consecutive patients with RA in usual rheumatology care between 1980 and 2004 at two settings for the proportion of patients taking MTX, interval from patient presentation to MTX prescription and radiographic and functional status outcomes.
METHODS: Longitudinal study of all patients seen in usual care between 1980 and 2004, 1982 consecutive patients in Jyväskylä, Finland and 738 consecutive patients in Nashville, TN, USA. Clinical status was assessed as Larsen radiographic scores in Jyväskylä and modified health assessment questionnaire (MHAQ) in Nashville.
RESULTS: The probability of initiating MTX within 5 yrs after presentation increased from <5% in Jyväskylä before 1989 to >90% in 2000-04, and from 25% in Nashville in 1980-84 to >90% since 1995. The median interval from presentation to MTX initiation in Jyväskylä was 14 yrs in 1980-84 vs 8.6 in 1985-89, 4.5 in 1990-94, 1.8 in 1995-99 and <1 yr in 2000-05; in Nashville, median intervals were 8.6 yrs in 1980-84, 4.4 years in 1985-89, and <2 months in 1990-95, 1995-2000 and 2000-05. Patient outcomes were substantially improved in both settings: in Jyväskylä, mean 5-yr Larsen radiographic scores (0-100) were 15.7 in 1980-84 vs 4.0 in 1995-99; in Nashville, mean MHAQ scores (0-3) for physical function were 1.13 in 1980-84 vs 0.57 in 2000-04.
CONCLUSION: Early MTX in usual clinical care of RA increased from <5% in 1980 to >90% in 2004. Over this period, substantially improved outcomes were seen, most of which antedated biological agents.
OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA).
METHODS: MTX-naive patients with active RA (Disease Activity Score in 28 joints >or= 4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n=187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n=188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks.
RESULTS: At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >or= 12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups.
CONCLUSION: This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability.
We report the case of a patient receiving subcutaneous methotrexate (MTX) treatment for rheumatoid arthritis (RA) who developed a complex pattern of neurological and pulmonary symptoms. Fluctuant dysarthria, magnetic gait, weakness and dysmetria of the lower limbs, as well as symptoms and signs consistent with a diagnosis of pneumonitis started within 6 weeks of initiating MTX treatment and slowly resolved after its discontinuation. This case highlights the fact that even the relatively low doses of MTX in the therapy of RA can produce neurotoxicity, which can become manifest in a broad range of symptoms.
Veintiocho pacientes con artritis reumatoide refractaria completado un estudio aleatorizado de 24 semanas doble ciego, cruzado comparando el metotrexato oral (2,5 a 5 mg cada 12 horas por tres dosis semanales) con el placebo. El grupo de metotrexato tuvieron reducciones significativas (p menos de 0,01, en comparación con el grupo placebo) en el número de articulaciones sensibles o dolorosas, la duración de la rigidez matinal y la actividad de la enfermedad de acuerdo a las evaluaciones médico y el paciente a las 12 semanas de la visita de cruce; reducciones en el número de articulaciones inflamadas (P menor que 0,05) y de 15 metros Tiempo del recorrido (P menor que 0,03) también estuvieron presentes. Estas variables, así como la fuerza de agarre y velocidad de sedimentación globular, mostraron significativas (P menor que 0,01) la mejora a las 24 semanas en la población pasaron a metotrexato. Una frecuencia significativamente mayor (P menor que 0,03) del haplotipo HLA-DR2 se produjo en los ocho pacientes con la respuesta más importante con el metotrexato. Las reacciones adversas durante el tratamiento con metotrexato incluyen elevación de las transaminasas (21 por ciento), náuseas (18 por ciento) y diarrea (12 por ciento), un paciente fue retirado del estudio debido a la diarrea. Un paciente falleció mientras recibía el placebo. El metotrexato no afecta a las medidas de la inmunidad humoral o celular. Concluimos que esta prueba proporciona evidencia de la eficacia a corto plazo de metotrexato en la artritis reumatoide, pero el mecanismo de acción es desconocido. Pruebas más largas se requiere para determinar la máxima seguridad y eficacia de este medicamento.
To analyse consecutive patients with RA in usual rheumatology care between 1980 and 2004 at two settings for the proportion of patients taking MTX, interval from patient presentation to MTX prescription and radiographic and functional status outcomes.
METHODS:
Longitudinal study of all patients seen in usual care between 1980 and 2004, 1982 consecutive patients in Jyväskylä, Finland and 738 consecutive patients in Nashville, TN, USA. Clinical status was assessed as Larsen radiographic scores in Jyväskylä and modified health assessment questionnaire (MHAQ) in Nashville.
RESULTS:
The probability of initiating MTX within 5 yrs after presentation increased from <5% in Jyväskylä before 1989 to >90% in 2000-04, and from 25% in Nashville in 1980-84 to >90% since 1995. The median interval from presentation to MTX initiation in Jyväskylä was 14 yrs in 1980-84 vs 8.6 in 1985-89, 4.5 in 1990-94, 1.8 in 1995-99 and <1 yr in 2000-05; in Nashville, median intervals were 8.6 yrs in 1980-84, 4.4 years in 1985-89, and <2 months in 1990-95, 1995-2000 and 2000-05. Patient outcomes were substantially improved in both settings: in Jyväskylä, mean 5-yr Larsen radiographic scores (0-100) were 15.7 in 1980-84 vs 4.0 in 1995-99; in Nashville, mean MHAQ scores (0-3) for physical function were 1.13 in 1980-84 vs 0.57 in 2000-04.
CONCLUSION:
Early MTX in usual clinical care of RA increased from <5% in 1980 to >90% in 2004. Over this period, substantially improved outcomes were seen, most of which antedated biological agents.
