Excellent 10-Year Outcomes After Early Treat-to-Target in Rheumatoid Arthritis

— New study bolsters recommendations to base initial treatment on clinical response

Most patients with rheumatoid arthritis (RA) whose initial treatment used a stringent treat-to-target strategy in a clinical trial were in remission 10 years later, with only modest radiographic progression over that time, researchers said.

With 179 of the 218 surviving original participants available for 10-year follow-up, 82% met strict criteria for clinical remission, according to Lena Bugge Nordberg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, and colleagues.

Moreover, the median change in modified van der Heijde-Sharp score for radiographic damage was just 2.0 points (IQR 0.5-4.5). With scores averaging 0.5 at baseline, and a maximum possible score of 448, the authors called this degree of progression "limited" in their report, appearing in Annals of the Rheumatic Diseasesopens in a new tab or window.

These findings, the investigators wrote, "support current treatment recommendations for RA and offer reassurance to patients newly diagnosed with RA that clinical remission, preserved function, and favorable long-term survival are realistic long-term outcomes."

Treat-to-target (TTT) is now the recommended approach for RA. Drug doses are titrated to achieve clinical benchmarks such as remission, limited only by tolerability, instead of adhering strictly to dosages listed on the medications' labels. Numerous studies have established that the TTT strategy improves short- and medium-term outcomes, but what happens after a decade or longer is still being examined. One long-term study reported in 2024opens in a new tab or window showed that outcomes from early TTT were still good as long as 20 years after starting therapy, although it involved participants in two separate Dutch trials that used different TTT strategies.

The current study followed participants in a Norwegian trial called ARCTICopens in a new tab or window, whose initial results were reported in 2016opens in a new tab or window. It enrolled 230 patients who were randomized to two similar TTT strategies: both had clinical remission as the target, but one also included completely negative ultrasound findings of inflammation at all joints tested. As it happened, the super-stringent approach using ultrasound showed no significant advantage over the conventional TTT.

Nordberg and colleagues therefore included all participants from ARCTIC for the 10-year follow-up. Twelve patients had died during that period (about as many as expected from general population statistics), leaving 218 who could be invited for a new exam. For various reasons, 39 were unable or unwilling to participate, leaving 179 with 10-year outcome data.

Remission, both in the original trial and the follow-up, was defined as a Disease Activity Score (DAS) less than 1.6; this index involves a 44-joint assessment for swelling, erythrocyte sedimentation rate, scores on the Ritchie Articular Indexopens in a new tab or window for tender joints, and patients' global assessment on a 100-point scale.

Mean DAS value at ARCTIC's original baseline was 3.4, which fell to 1.2 at year 2. At year 10, the average stood at 1.1. Both at year 2 and year 10, some 80% of patients had no Doppler signal in any joint.

One factor did divide these patients into better versus worse responders. Those who had achieved clinical remission (DAS <1.6) at year 2 were significantly more likely to keep that status at year 10 (89.9%), compared with those with poorer short-term outcomes (73.1%, P=0.01). Other outcomes including the more conventional 28-joint DAS, ultrasound findings, ACR/EULAR 2.0 remissionopens in a new tab or window, and measures of systemic inflammation all showed significantly more disease activity at year 10, albeit still generally low, among those not reaching remission at year 2.

Notably, most patients were still under active treatment after 10 years, although 15% had actually stopped all disease-modifying anti-rheumatic drugs (DMARDs). About 44% were on a single conventional DMARD, almost always methotrexate; 35% were taking a biologic product or other targeted agent; and a handful used multiple conventional DMARDs. Sixteen patients were using prednisolone, at a mean dose of 6.2 mg/day.

An important limitation to the study was that patients were left on their own between years 2 and 10, and the treatments they received during this period may have influenced the results. ARCTIC had no non-TTT control group for comparison. As well, some patients also participated in a substudy that examined withdrawal of biologic agentsopens in a new tab or window after achieving remission, and their 10-year outcomes were included in the current analysis.