Initiating disease-modifying antirheumatic drugs within 6 months of a diagnosis of rheumatoid arthritis is associated with significantly lower disability scores over the long term, new research suggests.

Better diagnosis and access to early treatment has also likely played a role in a global decline in mortality from rheumatoid arthritis over a recent 25-year period, according to an analysis of World Health Organization and United Nations data, but the decline has occurred unequally across countries.

Impact of early treatment on disability

In the first of two separate studies published online April 20 in Arthritis & Rheumatology, U.K. researchers followed 602 patients from the Norfolk Arthritis Register for 20 years, starting in 1990-1994, and collected clinical data at baseline and years 1-3, 5, 7, 10, 15, and 20.

Their analysis suggested that patients who did not receive treatment with disease-modifying antirheumatic drugs or steroids until at least 6 months after being diagnosed had significantly higher Health Assessment Questionnaire–Disability Index scores than did those who were not treated, after the researchers accounted for baseline clinical variables and other factors including smoking status and comorbidities.

However, patients who began treatment within 6 months of diagnosis had disability scores similar to those of patients who were never initiated on treatment ( Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40090 ).

“This supports the importance of the “window of opportunity” construct for treatment, showing that early treatment leads to improved outcomes even into the second decade following symptom onset,” wrote first author James M. Gwinnutt, a PhD candidate at the University of Manchester (England), and his coauthors. “Increased functional disability over time could be due to worse joint damage, and it has been shown that those who receive later treatment have higher radiological scores at follow-up than those treated early.”

There were 88 deaths in the early treatment group (55%) during the follow-up period, 99 deaths (39.8%) in the late treatment group, and 78 deaths (40.4%) in the never-treated group.

When the researchers adjusted for disease severity in a comparison of mortality across the groups, they found a trend toward a reduced risk of mortality in patients treated early, compared with those who began treatment later, although this did not reach statistical significance.

However, patients in both the early treatment and late treatment groups showed significantly elevated standardized mortality rates, compared with the general population of Norfolk, while the never-treated group showed slightly – but not significantly – elevated mortality.

Overall, around one-quarter of patients (26.6%) began treatment within 6 months of the onset of symptoms, 19.9% were started on treatment within 6-12 months, 17.4% started within 1-2 years, 19% did not start treatment until more than 2 years after symptom onset, and 43.7% of the cohort never received treatment but still attended follow-up.

Patients who began earlier treatment had worse clinical characteristics than did those who began treatment later, except for tender joint counts and autoantibody status.

Researchers saw an overall decline in median swollen joint count and tender joint count in the first year after baseline, and this remained low throughout the course of the study.

Median Health Assessment Questionnaire scores also fell after baseline but then increased steadily from year 2 to year 20, exceeding baseline levels by year 7.

“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,” the authors wrote.

An uneven global decline in mortality from RA

Meanwhile, a second study showed that mortality from rheumatoid arthritis declined globally across 31 countries from 1987 to 2011, according to data from the World Health Organization mortality database and the United Nations.

The absolute number of deaths where rheumatoid arthritis was registered as the underlying cause of death declined from 0.12% of all-cause deaths in 1987 to 0.09% of all-cause deaths in 2011 ( Arthritis Rheumatol. 2017 April 20. doi: 10.1002/art.40091 ).

The mean age-standardized mortality rate declined by 48.2%, from 7.1 per million person-years in 1987-1989 to 3.7 in 2009-2011.

However, there was considerable variation between countries; the greatest reduction was seen in Finland, which had an absolute reduction of 20.6 fewer deaths per million person-years, while Croatia had an increase of 3.7 deaths per million person-years.

Younger people with rheumatoid arthritis showed the greatest reductions in mortality, while those in older age groups had smaller reductions in mortality.

“It has been suggested that changes in the management of RA toward early and aggressive treatment with disease-modifying antirheumatic drugs and subsequent biologic therapies has led to better health status and lower mortality for most people with RA over time,” wrote first author Aliasghar A. Kiadaliri, PhD, of Lund (Sweden) University, and his coauthors.

“These findings alongside aging of the population and fall in mortality may lead to an increase in the number of people with RA. Given that it appears that people with RA are now living longer, increase in burden of RA on health care systems is expected and policy makers should be made aware about to appropriately plan for this anticipated increase.”

The first study was supported by Arthritis Research UK. The second study was supported by the Swedish Research Council, Crafoord Foundation, Greta and Johan Kocks Foundation, the Faculty of Medicine Lund University, governmental funding of clinical research within Sweden’s National Health Service. No conflicts of interest were declared for either paper.


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