Early Treatment in RA Can Lessen Disability


Study of long-term outcomes in rheumatoid arthritis supports early window of opportunity treatment theory.

Researchers in the United Kingdom report that early treatment after onset of rheumatoid arthritis improves long-term outcomes of disease activity and premature mortality.

In the study, published online April 20 in Arthritis & Rheumatology, the study team evaluated associations between the timing of treatment and disease activity, mortality and disability over a 20-year time period.

Led by Suzanne Verstappen, Ph.D., of the University of Manchester in the United Kingdom, researchers explored the effects of early, late and no treatment on key outcomes in sample of 602 patients from the Norfolk Arthritis Register in the United Kingdom.

“This paper has two important messages, firstly about the long-term outcome of patients with RA in the modern era treated according to best practice at the time of presentation; secondly, about the benefit of early treatment which is still apparent into the second decade after symptom onset with respect to functional disability,” wrote Verstappen and colleagues.

Early rheumatoid arthritis is a subset of inflammatory polyarthritis and is predominantly characterized by synovial joint inflammation. Patients with rheumatoid arthritis are at risk for joint destruction and premature death. To date, few studies have evaluated the long-term outcomes of patients with rheumatoid arthritis.

Methotrexate has become the first choice synthetic disease modifying anti-rheumatic drug (sDMARD) and several biologic DMARDS (bDMARDs) have been introduced since 2000. Examining long-term outcomes in this patient population is critical given the new advances in treatments and disease management strategies that have emerged over time. These advances have prompted a focus among clinicians for starting sDMARD therapy early in the disease trajectory. Specifically, more attention has been given to treating patients within a “window of opportunity” to maximize positive outcomes.

The study

This was a retrospective analysis of 602 patients in the Norfolk Arthritis Register recruited between 1990-1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. Patients in the study were either referred by a primary care physician or consultant rheumatologist, were at least 16 years of age, and had at least two swollen joints lasting at minimum four weeks. Assessments were conducted at baseline and at one, two, three, five, seven, 10, 15 and 20 years. Primary outcomes included disease activity, mortality and disability.

Patients were classified into one of three treatment groups with treatment being sDMARDs and steroids. The first group received treatment at or less than six months after symptom onset or early treatment. The second group received treatment 6 months or more after onset or late or never having received treatment.

In total, 160 (26.6%) patients received early treatment within six months of symptom onset. Of these, 94 (58.8%) were prescribed sulfasalazine, 45 (28.1%) were prescribed steroids, 8 (5%) were prescribed MTX, and 13 (8.1%) were prescribed medications other DMARDs. Patients who received early treatment had worse clinical characteristics on all baseline variables compared with the late treatment or never treatment groups. Of the remaining patients, 88 (19.9%) received their first treatment within six to 12 months, 77 patients (17.4%) received treatment within one to two years, and 84 patients (19.0%) received treatment after two years after symptom onset. Approximately 193 patients, or 43 percent, never received treatment while attending follow-up.

The main findings were that patients who received either early treatment or late treatment had reduced mortality risk compared to the never treatment patients. Moreover, median disease activity was generally low over follow-up.

Although disability rose after the first year, it still remained at low or moderate levels after year 10. The early treatment group had comparable disability compared to the never treatment group over follow-up (β 0.03, 95% CI -0.06, p=0.12); however, the late treatment group had increased disability compared to the never treatment group (β 0.10, 95% CI 0.02, p=0.17).

One limitation of this study is that treatment practices for rheumatoid arthritis changed over the 20-year time period.

“Nevertheless, these results are still important as they show a clear improvement from patients studied in the 20-year period before this, and that early treatment with predominantly sulfasalazine or steroids is associated with improved outcomes 20 years later. Thus, as methotrexate is considered a more effective treatment than sulfasalazine, the benefits 20 years later of early treatment with methotrexate maybe even greater,” wrote Dr. Verstappen and the study team. 



This research was funded by Arthritis Research UK.



James M. Gwinnutt, Deborah P.M. Symmons, Alexander J. MacGregor, et al. "The 20 year outcome and association between early treatment and mortality and disability in an inception cohort of patients with rheumatoid arthritis: results from the Norfolk Arthritis Register," Arthritis & Rheumatology. Published online April 20, 2017. DOI: 10.1002/art.40090.

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