Rheumatoid Arthritis, Aging, and Biologics: Good News

Rheumatoid arthritis (RA) most commonly arises in middle age or beyond. With the new focus on aggressive treatment to prevent future joint erosion, whether age at onset influences either disease severity or treatment effectiveness has emerged as an important issue in research.

Some studies categorize RA by a threshold set at age 60: Young-onset RA (YORA) presents before age 60 and late-onset RA (LORA) after that age.

While some differences emerge in antibody levels and disease severity, recent studies indicate both groups need to be treated aggressively. And new research presented at the 2014 meeting of the European League Against Rheumatism (EULAR) suggests that etanercept (Enbrel), the tumor necrosis factor-alpha (TNF α) inhibitor most commonly used to treat RA, is just as effective in older RA patients as in younger ones.¹

Older vs. Younger

Depending on the specific population studied, the average age of onset for RA ranges from the mid-to late-50s, and complications increase with increasing age.

Swiss researchers comparing YORA with LORA patients, most of them women, found that RA peaks at age 54, and that older patients having more joint erosions.² Data from Britain shows the average age at RA onset is now around 58.5, with lower mortality among younger RA patients.³ Also, recent Canadian data finds the highest incidence and prevalence of RA in the 55- to 85-year-old age group, often with associated co-morbidities, polypharmacy, and long-standing disease.¹

While RA patients over age 60 (LORA) seem to have more affected joints, slightly higher disease activity scores, and more comorbidities than YORA patients, the Swiss researchers find no reasons to think there’s an age-related form of RA.²

The study compares recent-onset YORA patients (n=366) with LORA patients (n=266) in the Swiss RA registry/Swiss Clinical Quality Management in RA cohort, over a five year period.

Among the cohort, most of whom are women, older patients had greater joint erosion at onset than younger patients (mean Ratingen scores of 12.7 and .6, respectively) but joint damage seen on X-rays progressed at similar rates in both groups. Disease activity scores in 28 joints (DAS28) decreased in both groups over time, but the initial differences disappeared after 6 months and during follow-up.

The first study to look at the impact of age at menopause on RA severity found that a women who enter menopause before age 46 seem to have a milder form of the disease, with fewer erosions, lower scores on the health assessment questionnaire (HAQ), and less likelihood of progressing to severe RA.⁴

The 2012 retrospective Swedish study classified 134 women (mean age at RA diagnosis 63.4) by severe RA, mild/moderate rheumatoid factor (RF) positive RA, or mild/moderate RF-negative RA. More younger women fell into the latter two groups.

All 26 women with severe RA had been treated with biologics, 89% were RF positive, and 85% had documented radiographic erosions, with a mean HAQ score after 5 years of 1.17.

In contrast, none of the 54 women in the RF-positive and RF-negative mild/moderate RA clusters had received biologics, around half had documented erosions, and the age-adjusted mean HAQ scores after 5 years were much lower (0.74 and 0.88, respectively).

“Hormonal changes may influence pathways that are distinct from those leading to severe, progressive disease,” the authors suggest.

Treatment Differences

In the Swedish study, greater disease severity among women with a later menopause apparently led to biologic and combination DMARD treatment.

However, in the Swiss study, differences in treatments between younger and older RA patients seem to be related to physician preference and comorbid conditions.

The LORA patients were treated more frequently with corticosteroids than YORA patients (68% vs. 25.4%). Older patients also had fewer changes in treatment, suggesting the greater number of comorbid diseases they developed may have negatively influenced decisions to use newer therapies, including biologics.

However, older age and longer disease duration do not appear to lessen the effectiveness of biologics, say Canadian researchers.

They conducted a retrospective analysis of 72 older RA patients given the TNFα blocker etanercept for a minimum of three months at a rheumatology clinic in Hamilton, Ontario between Jan 2004 and Dec 2011. A majority were women in their mid-70s (mean age=73) and RF-positive. Over half of the patients were still taking etanercept at the end of the study.¹

Judging by changes in swollen and tender joint counts, etanercept was effective even after age 80. Overall, patients showed significant improvement in swollen joint counts (SJC) over 23 months, with progressive declines in mean SJCs from baseline to 3 months (8.45 to 4.56), at 13 months (2.56), and at 23 months (1.85).

Patients with early and long-standing RA show similar sustained improvement in disease activity, with a drop in concomitant use of DMARDs, the Canadians told the 2014 EULAR meeting.

Possibly the best news for patients of any age: thanks to treatment advances in the past 25 years people with RA may now enjoy as much as an extra decade of life.

Research from two RA registries in the UK, encompassing more than 2,700 patients between 1986 and 2012, estimates the average life expectancy in RA at 86.7 years. That’s compared to 76.8 years, the average age at death back in 1998, according to a study reported at the 2014 meeting of the British Rheumatology Society.³

References:

1.  Lau AN, Shah A, Deamude M, et al.Does etanercept maintain its efficacy in the elderly population. A single center retrospective analysis. EULAR 2014, Abstract AB0221. Ann Rheum Dis. (2014) doi: 10.1136/annrheumdis-2014-eular.6068

2.  Mueller RB, Kaegi T, Finckh A, et al., Is radiographic progression of late-onset rheumatoid arthritis different from young-onset rheumatoid arthritis? Results from the Swiss prospective observational cohort.Rheumatology (Oxford) (2013) Dec 17. doi:10.1093/rheumatology/ket399.

3.  British Society for Rheumatology 2014, Annual Meeting (BSR 2014), Abstract #034: Norton S, et al. "Excess mortality in rheumatoid arthritis: gains in life expectancy over 25 years." Rheumatology 2014 Abstracts. Volume 53 suppl 1. April 2014 i69-i70 doi:10.1093/rheumatology/keu097.006.

4.  Pikwer M, Nillson JA, Bergström L, et al.  Early menopause and severity of rheumatoid arthritis in women older than 45 years. Arthritis Research & Therapy 2012, 14:R190. doi:10.1186/ar4021.