Is the Impact of Methotrexate On Mortality in Rheumatoid Arthritis Independent of Its Effect On Disease Activity?

Dietmar MJ Krause¹, Bernadette Gabriel², Gertraud Herborn³ and Rolf Rau⁴, ¹Internistische und rheumatologische Gemeinschaftspraxis, Gladbeck, Germany, ²Private Practice, Gladbeck, Germany, ³Rheumatology, Evangelisches Fachkrankenhaus, Ratingen, Germany, ⁴Evangelisches Fachkrankenhaus, Ratingen, Germany

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: methotrexate (MTX), morbidity and mortality and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis - Clinical Aspects I: Drug Studies/Drug Safety/Drug Utilization/Disease Activity & Remission

Session Type: Abstract Submissions (ACR)

Background/Purpose: Methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA). MTX shows effects on disease activity, radiologic progression and mortality. These three effects are thought to be associated with each other. Therefore, MTX-treatment is often stopped in case of insufficient improvement of disease activity. However, this association is incompletely understood.

Methods: We analysed data of one of the earliest MTX-cohorts in Europe (Evangelisches Fachkrankenhaus Ratingen). From 1980 to 1987 all patients starting treatment with MTX (n=271) were enroled in a prospective observational study. One year after baseline, response to MTX-treatment was determined (improvement or no improvement of at least 20%). Nearly all patients continued MTX-treatment independent of this response (due to lack of alternative treatments). In 1995 and 2003, the follow-up of 250 patients could be determined. Cox regression was applied to estimate risks for increased mortality.

Results: Ten years after baseline, 88 patients were deceased, 64% of the patients alive were still on MTX-treatment. 59 patients died in the following eight years. A Cox model with age, gender, response to MTX-treatment after one year, number of swollen joints ten years after baseline and continuation of MTX-treatment as covariates showed independent positive effects of continued MTX-treatment on mortality (hazard ratio (HR): 0,63; 95%-confidence interval (CI): 0,44-0,89, p = 0,009). In the group of non-responders the HR was 0,41 (95% CI 0,14 – 1,16), significance was missed due to the small number of patients in this group (n=23)

Conclusion: In this cohort, there are hints of a mortality lowering effect of MTX that is independent of its effect on disease activity. This might have consequences for treatment decisions in RA patients with insufficient MTX-efficacy on disease activity.

Disclosure:

D. M. Krause,
None;

B. Gabriel,
None;

G. Herborn,
None;

R. Rau,
None.

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