Is the disease course of rheumatoid arthritis becoming milder?

Rheumatoid arthritis (RA) is a chronic inflammatory disease, marked with joint pain and erosion. The course of RA can vary considerably, from mild to crippling, and is difficult to predict. On the strength of patient case histories and clinical trials, rheumatologists have suggested that the majority of today's RA patients are suffering less severe symptoms and less functional disability compared with RA patients in past decades.

Is the course of RA becoming milder? If so, why? Intrigued by these questions, researchers in The Netherlands decided to seek out the answers through a rigorous investigation. Published in the September 2005 issue of Arthritis & Rheumatism, their findings indicate a positive trend. "Patients with early RA presenting in recent years have less severe disease activity at presentation, as well as a more favorable course of their disease, compared with patients in earlier years," states the study's leading author, Paco M. J. Welsing, MSc.

What is the reason for this improving trend? Welsing and his colleagues found no clear, conclusive cause, and even uncovered some contradictory evidence. However, the team found a concurrent tendency toward a shorter duration of symptoms at the time of diagnosis and more aggressive use of drug therapy--for instance, methotrexate, today's preferred disease-modifying anti-rheumatic drug (DMARD) and/or prednisone--over the course of the disease.

The study included all newly diagnosed, early RA patients enrolled in the department of rheumatology clinic of Radboud University Nijmegen Medical Centre since 1985. Patients were divided into four groups based on the date of enrollment. Patients enrolled between 1985 and 1990 (167 total) comprised Group 1. Patients enrolled between 1990 and 1995 (132 total) comprised Group 2. Patients enrolled between 1995 and 2000 (114 total) comprised Group 3. And patients enrolled between 2000 and 2005 (112 total) comprised Group 4. In all groups, the majority of patients were women. The mean age at the time of enrollment was 54 years for Group 1; 55 years for both Groups 2 and 3; and 57 years for group 4.

Researchers set out to compare disease activity and functional disability among the groups over a 5-year progression (but 4-years, maximum, for Group 4). They also compared treatment strategies among the groups. All patients were assessed for signs of RA activity--namely, swelling and tenderness--in 28 joints every 3 months, a laboratory measure for inflammation and a measure of general well being by the Disease Activity Score 28 (DAS28). All patients were assessed for functional disability--covering difficulties with walking and conducting everyday activities--using the Health Assessment Questionnaire disability index (HAQ DI) every 6 months. In addition, all patients were periodically evaluated for pain in general.

The DAS28 scores at baseline and over the course of the study were consistently lower, indicating milder disease activity, in the more recent groups--that is, patients diagnosed with RA within the last ten years. At the 5-year culmination, the DAS28 scores were lowest in the most recent, complete group--Group 3, patients diagnosed between 1995 and 2000--compared with both Group 2 (1990-1995) and Group 1 (1985-1990). The average disease activity over time per patient showed similar trends of improvement. The average DAS28 score improved from 4.1 to 3.4 from the Group 1 to Group 3.

However, the HAQ DI scores at baseline and over time were not lower among patients enrolled later in the study, and even showed some evidence of a worsening trend. "This contradictory result may be partly a distinction between measures of physical examination, laboratory results, and patient-assessed outcomes," notes Welsing, "which can be influenced by internal standards or attitudes of patients."

Researchers did find a correlation between more aggressive treatment strategies and milder disease activity in the more recent groups of patients. While suggesting the effectiveness of early treatment with methotrexate, for instance, and/or prednisone for managing RA's symptoms and destructive progression, this connection calls for further investigation.