A new study leads back to the age-old question of incidence vs. diagnostics.
Rheumatoid arthritis (RA) research contains a series of mysteries. According to some studies, it’s on the decline; others, it’s on the rise. There seems a verifiable uptick in the number of people being diagnosed at a later age. But does this mean those people were exposed to something years ago that caused RA, or that the condition is on the decline in general, an issue of evolving diagnostics, comorbidities like obesity, or something else?
A new study in the January issue of Arthritis Research and Care explores the issue, suggesting that the average age of RA symptom onset is increasing, while severity remains relatively stagnant.
The study examined a quarter century of data drawn from two studies in over two dozen centers in the UK. The Early Rheumatoid Arthritis Study (ERAS) recruited over 1,400 patients between 1986 and 2001, with a median follow-up period of 10 years (though some patients were followed for up to 25 years).
The Early Rheumatoid Arthritis Network (ERAN) continued this work, recruiting over 1,200 patients between 2002 and 2012. The median follow-up period was six years with a maximum of 10. Both cohorts were about two-thirds female (66.4% and 67.9%).
At recruitment, ERAS patients were all disease-modifying rheumatic drug (DMARD) naïve, while a small, identified portion of the later ERAN cohort had initiated such treatment prior to joining the study. There were some minor differences in recruitment variables that had to be synthesized, as the earlier of the two studies used a 3-variable version of the 28-joint Disease Activity Score (DAS28) whereas the ERAN study used a 4-variable version. The researchers did use a conversion formula, but the two are not interchangeable, and were examined in the two cohorts as such.
The team derived a great deal of information from the studies. The findings concurred with other research in the journal showing a substantial increase in the likely presence of a comorbidity over time, from 29.0% in 1990 to 50.7% in 2010. Obesity was perhaps the most increasingly evident comorbidity.
From 1990 to 2010, however, they found that the average age of diagnosed RA symptoms increased by four and a half years, from 53.2 years old to 57.5.
There’s a wealth of possible explanations for this phenomenon that the authors explore, most intriguingly the notion that “the later onset age of RA observed in this study may indicate decreasing RA incidence,” pointing to a few studies the authors believe show a similar trend, “suggesting a birth cohort effect…a decreasing likelihood of developing RA with successive generations.” They point to a shift in the entire age distribution in the study over time, with standard deviations and clinical variables remaining constant, as a counterargument to alternate explanations.
Those alternate explanations mostly relate to diagnostics. Before arguing against it, the authors mention that some might think their results could just show “a gradual lowering of the clinical threshold for diagnosing RA in older people, pointing towards a period effect rather than a cohort effect.” They also briefly touch on the chance that it’s a decrease in people being diagnosed, perhaps due to access, but then mention that, demographically, there was little variation in the proportion of their mostly-female cohort living in “socially deprived areas” over the two-plus decades studied.
Countless previous studies have argued there is a birth cohort effect when it comes to RA onset age and incidence. A series of studies examining over 50 years’ worth of data from a single county in Minnesota showed fluctuation. The most recent, published in 2010, concluded that “incidence of RA appears to be rising in women during 1995-2007 period,” adding that “the reasons for this…are unknown, but environmental factors may play a role.”
While this study limited its hypotheses to a specific focus area and period and weighed environmental factors heavily, its authors spent little time considering differences in access to, and quality of, RA diagnostics between 1995 and 2007.
The preceding studies of that same county showed downward trends, however. One examining the period of 1950-74 showed a “substantial decline in RA incidence in women, but not in men,” and one observing the period of 1955-1985 showed a continuing overall decline. An article summing up the findings of the three reports pointed to studies from around the world that found fewer people in more recent generations had RA, but that it was being detected more in members of older generations, creating differences in age-onset statistics. Various environmental factors have been proposed, including contraceptive use, vitamin D deficiency, smoking rates, and air quality.
Millennia worth of patient-years in these studies from England, Minnesota, and around the world contain a wealth of data, and reinforce a few things: the burden of comorbidities, the importance of environmental factors and generations, and the disease’s enduring preference for female victims. When it comes to determining whether cases of rheumatoid arthritis are rising, falling, or holding steady, however, rheumatology may need more time.
The initial study, entitled "Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States", appears in the January issue of Arthritis Care and Research, which focuses on comorbidities and rheumatic diseases.