Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab

Abstract

Objectives: To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival.

Methods: Data of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking.

Results: During 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28 > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97).

Conclusions: Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.

Keywords: DAS28; DMARDs (biologic); Methotrexate; Rheumatoid Arthritis.

Figure 1

Flow chart of patients enrolled. Censored: patients who were in this study on 31 December 2011 but did not complete a follow-up period of 9 years since they were enrolled after January 2003. The follow-up time of these patients was censored at the last regular study visit. Dropouts: patients lost to follow-up.

Figure 2

Five-year survival rates (in %) for patients with highly active disease (DAS28 scores >5.1 at ≥80% of the observation time (18% of patients) and low disease activity (DAS28 scores <3.2 for ≥80% of the observation time (9% of patients) CHD: coronary heart disease.