Treat to Target Works in Elderly Onset RA Save

This is Jihal Lee from Michigan reporting for RheumNow in London for EULAR 2026. I'm going to be discussing what is a GSM to my passion which is aging and rheumatology. This is poster number 1326 looking at um to show that treat to target works in elderly onset RA and if anything that they need less to get there.

So older adults with RA are often undertreated and in clinical practice there's a tendency to kind of be hesitant about prescribing for concerns about tolerability risk because older adults have more comorbidities and there's some assumption um regarding safety and efficacy although there's been a number of studies to show that our drugs even the biologic and targeted synthetics are pretty well tolerated in older adults.

So, I was really excited to see this study to really get at the question of does treat to target work. So, by ways of a little bit of a background, um, elderly onset RA is defined as RA diagnosed on or after the age of 65. And I want to put in a little bit of a plug here because the American College of Geriatrics tries to avoid words that catastrophize aging. So, their preferred term is late onset rather than elderly onset. Um so it's really interesting to see there's some difference regarding terminology and I think this is one way in which um having a unified term approach is how we can also improve care of our aging population because the population is aging.

Um in Europe they're saying by 2050 um at least one third are going to be over the age of 65. Um I believe in the US that number is by 2030 we're going to be um one in four are going to be older adults. So this is going to be the norm of our study and I think RheumNow actually shows that 40% of all clinical patients are over the age of 65. So this is our reality and our challenge.

So it's really important to understand and get data on these because older adults often are not included in trials that actually inform our guidelines. So um with that there's also some clinical differences between those with um late onset um forgive me if I say late instead of elderly um late onset versus younger onset in that these patients tend to have more abrupt systemic um presentation, tend to be more seronegative. There tend to be less of a gender difference. So instead of the typical 3:1 or 4:1 it tends to be 2:1. So it's important not to underdiagnose our older male patients. And also there have been some studies to show that they have higher levels of IL-6 and lower levels of TNF. So clinically physiologically they tend to be a little bit different. Um and also at the time of diagnosis they're more likely to have comorbidities and polypharmacy adding to the challenge of treating these patients.

Um, but the question I like I said for these authors and they're from the Netherlands was can older adults achieve disease remission or low disease activity with a treat to target approach to really challenge the assumptions as I said that some physicians have because there was a study on ageism where interestingly most rheumatologists said they were not ageist but those who did have that tendency were less likely to prescribe um our DMARDs and more lean towards symptomatic uh management with glucocorticoids and NSAIDs.

So with that um let me set up the study for you. So this data is from what they call the T-REACH trial. It's a multi-center stratified single blinded randomized control trial that was conducted in the Netherlands and it was enrolling patients who met classification criteria for RA and they were either categorized as elderly onset or young onset depending on the age at which they were diagnosed with RA and out of I believe they had a total of um just over 300. So 98 patients um had a mean age of 73 at the time of diagnosis meeting the elderly onset criteria and the rest were younger onset and their age um ranged between 18 to 65 and that means roughly about 25% were late onset. In the US in the Medicare population that number is about 30%, again I think that's reflective of the US being slightly older in general than the European um populations. Um for all of these um 327 patients um where the overall mean age was 48, they were followed um doing a um fixed protocol of a treat to target approach of treatment. Their DAS trajectories, their DMARD use, glucocorticoid use, biologic drug survival and DMARD-free remission along with adverse events were assessed over a 2-year period of time. Um which I think is um very nicely set up and impressive. And then they looked at stratified analysis based on autoantibody status at the end.

So taking each of the outcomes. So for disease activity um trajectories they were actually similar between the two groups. The mean DAS difference between elderly onset and young onset was only 0.03 which is very clinically negligible. And both groups actually achieved comparable rates of low disease activity over the follow-up period of 2 years. How did they do that? Did the treatment intensity differ? Um I
think this is where the importance comes and the authors note that appropriately as well. So for elderly onset RA patients, they needed significantly less intensive therapy to achieve the same low disease activity with an odds ratio of about 0.3. So like 60% less intensity compared to the young patients. And they were less likely to require biologics. And I think the value here is that this was a prospective data collection whereas in the US when we look at Medicare it's often a cross-sectional retrospective. So we find that they get less biologics and we don't know if that's because they didn't require it or that it just wasn't given to them. So I think it's reassuring and informative to see that in this type of study they really did not.

At the same time, just as a benchmark number, in the US about 13 to 15% of older adults are on biologics, and in this study their numbers were actually up into prescribing rates of like 25 to 30%. So they required less, however their overall prescribing rates were much higher than in the US.

Continuing on with that. So again in terms of the treatment intensity they were less, but in terms of drug survival in terms of discontinuation they were very similar in that older adults or elderly onset RA patients were well tolerant of biologic therapy as well.

In terms of adverse events, again this is important because safety is something that we very much care about. So elderly onset patients had higher rates of bone marrow depression or osteoporosis. Understandably, 15% versus 70%. Elevated creatinine — it could be from methotrexate intolerance or underlying CKD — that number being 8% to 2% compared to the younger onset. Younger onset patients did report more mood related disorders than anything.

In terms of the continuity of treatment though, the DMARD switches or the dose adjustments due to the adverse events did not differ overall between those two groups, indicating again that the overall drug tolerability is comparable, although in terms of absolute experiences older adults may report more.

So what does this mean clinically for us? I think this finding makes a clear case that treat to target is not only feasible in elderly onset RA, it may work better than we expect with less treatment exposure, especially in this group. They did some stratified analysis that seronegative patients — but again just keep in mind I think that seronegativity is just coming from the nature of what elderly onset RA patients usually present with, and it's reassuring to know that the adverse effects are really not different between these two.

So the practical message I hope to share with you is that we are progressively caring for an older generation of patients. So let's not withhold a treat to target strategy from these patients based on age alone. There's a saying in the geriatrics world that chronologic age does not equate to physiologic age. So there are other means and assessments that we can bring in.

There were actually a number of abstracts at EULAR about frailty and sarcopenia being a risk stratification model or even an outcome model for older adults. And yes, I was very pleased to see this — there was actually a whole entire session about aging, and I think what was most powerful is the patient voice. So there was a patient who had been diagnosed at 17 who came and shared what patients want, and what they want is to be able to independently age at home, to be able to have conversations about treatments and understand them within the context of their competing comorbidities, and devise a plan that fits in with their goals and priorities.

So I think this information and this study gives us some reassurance that our usual treat to target approach helps, so that we can have better shared decision-making.

In terms of just a few limitations: it is relatively small — again, for a prospective cohort I think 330 is good, but the numbers are somewhat small for certain subgroup comparisons, especially with the smaller disease or drug specific measurements as well. And this is a trial setting, so they had intense monitoring and hands-on support, so in the real world where adherence is different for our patients there may be some variance in terms of the findings as well.

With that, this was Jihali reporting for RheumNow in London for EULAR 2025. Thank you for listening.