Response to Methotrexate Predicts Mortality in Rheumatoid Arthritis up to 30 Years

Carolin Krause¹, Siegfried Wassenberg², Rolf Rau³, Gertraud Herborn⁴, Juergen Braun⁵ and Dietmar Krause⁶, ¹University Munster, Munster, Germany, ²Rheumaklinik, Themistocles Gluck hospital - Rheumazentrum Ratingen, Ratingen, Germany, ³Expert in Rheumatology, Düsseldorf, Germany, ⁴Evangelisches Fachkrankenhaus Ratingen, Ratingen, Greece, ⁵Rheumazentrum Ruhrgebiet, Herne, Germany, ⁶Dept. for Medical Informatics, Biometry and Epidemiology, Ruhr University, Bochum, Germany

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

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

Session Information

Date: Wednesday, November 11, 2015

Title: Rheumatoid Arthritis - Clinical Aspects VI: Death Be Not Proud-Mortality and Treatment Outcomes in RA (Includes 2014 Lee C. Howley, Sr. Prize for Arthritis Research Introductory Talk)

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose:

Methotrexate (MTX) is considered as the anchor drug for the treatment of patients with rheumatoid arthritis (RA). MTX has been shown to reduce disease activity and decrease radiographic progression and mortality. Response to MTX treatment is known to predict long term outcomes over some years. However, it is not clear whether this effect becomes weaker in the long-term.

Methods:

We analysed data of one of the earliest MTX-cohorts in Europe (Evangelisches Fachkrankenhaus Ratingen, Germany)¹. From 1980 to 1987, all patients starting treatment with MTX (n=271) were enrolled in a prospective observational study. One year after baseline, response to MTX-treatment was determined (improvement or no improvement of at least 20%). Re-evaluations were performed 10, 18, and 30 years after baseline. In 2015, outcomes of 192 patients (71%) could be assessed. Cox regression was applied to estimate risks for increased mortality. The Cox model included age, gender, rheumatoid factor, signs of disease activity at baseline (number of swollen joints, ESR), patient global assessment at baseline, and response to MTX treatment after one year.

Results:

30 years after baseline, 167 patients were deceased. A positive effect on mortality was seen for the response to MTX treatment after one year (hazard ratio (HR) 0.60; 95%-confidence interval (CI): 0.42-0.89, p = 0.007) (Table 1). Furthermore, in the group of patients still alive ten years after baseline continued MTX-treatment was associated with lower mortality (HR 0.95 per mg; 95%-CI: 0.91-0.98, p = 0.003) in the next 20 years.

Table 1. Predictors of all-cause mortality for the entire observation period

Variable	Hazard ratio	95% confidence interval	Chi-Square	p-value
Improvement ≥20% after the first year of MTX treatment	0.60	0.42 to 0.87	7.37	0.007
Age	1.09	1.07 to 1.11	76.3	<0.001
Female gender	0.76	0.52 to 1.10	2.11	0.146
RF positivity	1.20	0.71 to 2.02	0.44	0.507
No. of swollen joints at baseline (0 – 32)	1.01	0.99 to 1.03	0.77	0.379
ESR at baseline	1.00	0.99 to 1.01	2.40	0.121
Patient global assessment at baseline	1.20	0.80 to 1.81	0.80	0.370

RF: rheumatoid factor; MTX: methotrexate; ESR: erythrocyte sedimentation rate.

Conclusion:

In this cohort, response to MTX after one year of treatment was a predictor of lower mortality during the next 30 years. Continued MTX treatment after ten years was positively associated with lower mortality in the following 20 years.

Disclosure: C. Krause, None; S. Wassenberg, None; R. Rau, None; G. Herborn, None; J. Braun, Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 9,Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 9,Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, 5; D. Krause, None.

To cite this abstract in AMA style:

Krause C, Wassenberg S, Rau R, Herborn G, Braun J, Krause D. Response to Methotrexate Predicts Mortality in Rheumatoid Arthritis up to 30 Years [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/response-to-methotrexate-predicts-mortality-in-rheumatoid-arthritis-up-to-30-years/. Accessed .

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