Trends Toward Improved Disease State in RA: Analysis of the EMECAR Cohort
Trends Toward Improved Disease State in RA: Analysis of the EMECAR Cohort
Introduction: The disease activity in patients with rheumatoid arthritis has improved during the past decade. The availability of new drugs and also a better assessment of the disease have been proposed to be responsible for this improvement. In the present work we estimate the effect of these factors on disease activity and function in patients with rheumatoid arthritis at the beginning of the new century.
Methods: The Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide (EMECAR) cohort was assembled in 2000 from the random sampling of rheumatoid arthritis patients registered in 34 centers. The cohort was composed of 789 patients who underwent a baseline assessment plus four annual follow-up visits in which functional ability (Health Assessment Questionnaire score), the disease activity score obtained from 28-joint count with three parameters (DAS28-3) and radiological progression (Larsen score) were recorded. The effect of the calendar year on the DAS28-3, the Health Assessment Questionnaire score, and the Larsen score was obtained from adjusted models in which all treatments were included as dummy variables.
Results: The effect of time as the β coefficient (95% confidence interval) for 2004, taking 2000 as a reference year, was -0.43 (-0.58 to -0.28) for the DAS28-3, 0.15 (0.07 to 0.22) for the Health Assessment Questionnaire score, and 4.4 (2.68 to 6.12) for the Larsen score. Treatment with new therapies, either leflunomide or TNF antagonists, increased in frequency from 1.1% (n = 8) in 2000 to 30.9% (n = 144) in 2004. Treatment with TNF antagonists (-0.28 (-0.5 to -0.05)) and with gold salts (-0.21 (-0.38 to -0.04)) was independently associated with a decrease in the DAS28-3 over time, whereas cyclosporin A treatment (0.45 (0.13 to 0.76)) was associated with an increase in disease activity.
Conclusions: The mean disease activity of rheumatoid arthritis has improved from 2000 to 2004. An explanation is the introduction of new therapies, but not solely. Other factors related to the calendar year, plausibly a better management of available drugs, show a greater effect on improvement than the drugs used.
During the past decade, the number of therapeutic alternatives against rheumatoid arthritis (RA) has gratifyingly increased. Most of these new drugs belong to the so-called biologic agents, which have been developed against specific targets that play important functions in the pathogenesis of RA - namely, TNF, IL-1, CTLA-4, and CD20. Leflunomide (LEF) was introduced also in the past decade as a new nonbiologic disease-modifying antirheumatic drug (DMARD). TNF antagonists (aTNF) and LEF have demonstrated efficacy in randomized controlled trials, not only improving disease activity but also decelerating or arresting radiological damage. When used outside trials, however, the effectiveness of new drugs may differ, since patients included in clinical trials are younger on average, have less comorbidity, and show greater disease activity than real-life patients. In addition, drugs are prescribed according to strict protocols in clinical trials, while routine prescription is based not only on characteristics of the patients but also on physician's preferences.
While testing the hypothesis of a lower effectiveness of DMARDs and biologic agents in observational studies compared with clinical trials, we found that new drugs may have an impact - benefiting not only patients who are exposed to them, but also the nonexposed patients. The Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide (EMECAR) cohort was assembled before the widespread use of LEF and aTNF in Spain, during 1999 and 2000, and followed thereafter for four consecutive years, thus providing an adequate scenario to test hypothesis on new drugs. The present work describes what happened to RA patients followed up routinely in daily practice in terms of disease activity, disability and radiological progression in the time when LEF and aTNF were introduced.
Abstract and Introduction
Introduction: The disease activity in patients with rheumatoid arthritis has improved during the past decade. The availability of new drugs and also a better assessment of the disease have been proposed to be responsible for this improvement. In the present work we estimate the effect of these factors on disease activity and function in patients with rheumatoid arthritis at the beginning of the new century.
Methods: The Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide (EMECAR) cohort was assembled in 2000 from the random sampling of rheumatoid arthritis patients registered in 34 centers. The cohort was composed of 789 patients who underwent a baseline assessment plus four annual follow-up visits in which functional ability (Health Assessment Questionnaire score), the disease activity score obtained from 28-joint count with three parameters (DAS28-3) and radiological progression (Larsen score) were recorded. The effect of the calendar year on the DAS28-3, the Health Assessment Questionnaire score, and the Larsen score was obtained from adjusted models in which all treatments were included as dummy variables.
Results: The effect of time as the β coefficient (95% confidence interval) for 2004, taking 2000 as a reference year, was -0.43 (-0.58 to -0.28) for the DAS28-3, 0.15 (0.07 to 0.22) for the Health Assessment Questionnaire score, and 4.4 (2.68 to 6.12) for the Larsen score. Treatment with new therapies, either leflunomide or TNF antagonists, increased in frequency from 1.1% (n = 8) in 2000 to 30.9% (n = 144) in 2004. Treatment with TNF antagonists (-0.28 (-0.5 to -0.05)) and with gold salts (-0.21 (-0.38 to -0.04)) was independently associated with a decrease in the DAS28-3 over time, whereas cyclosporin A treatment (0.45 (0.13 to 0.76)) was associated with an increase in disease activity.
Conclusions: The mean disease activity of rheumatoid arthritis has improved from 2000 to 2004. An explanation is the introduction of new therapies, but not solely. Other factors related to the calendar year, plausibly a better management of available drugs, show a greater effect on improvement than the drugs used.
Introduction
During the past decade, the number of therapeutic alternatives against rheumatoid arthritis (RA) has gratifyingly increased. Most of these new drugs belong to the so-called biologic agents, which have been developed against specific targets that play important functions in the pathogenesis of RA - namely, TNF, IL-1, CTLA-4, and CD20. Leflunomide (LEF) was introduced also in the past decade as a new nonbiologic disease-modifying antirheumatic drug (DMARD). TNF antagonists (aTNF) and LEF have demonstrated efficacy in randomized controlled trials, not only improving disease activity but also decelerating or arresting radiological damage. When used outside trials, however, the effectiveness of new drugs may differ, since patients included in clinical trials are younger on average, have less comorbidity, and show greater disease activity than real-life patients. In addition, drugs are prescribed according to strict protocols in clinical trials, while routine prescription is based not only on characteristics of the patients but also on physician's preferences.
While testing the hypothesis of a lower effectiveness of DMARDs and biologic agents in observational studies compared with clinical trials, we found that new drugs may have an impact - benefiting not only patients who are exposed to them, but also the nonexposed patients. The Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide (EMECAR) cohort was assembled before the widespread use of LEF and aTNF in Spain, during 1999 and 2000, and followed thereafter for four consecutive years, thus providing an adequate scenario to test hypothesis on new drugs. The present work describes what happened to RA patients followed up routinely in daily practice in terms of disease activity, disability and radiological progression in the time when LEF and aTNF were introduced.
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