Ten-Year Follow-Up Shows Sustained Remission After Early Treat-to-Target Therapy in Rheumatoid Arthritis

• Early, strict treat-to-target management is a promising strategy for controlling rheumatoid arthritis (RA), though long-term data remain limited.
• Researchers assessed 10-year outcomes in a stringent treat-to-target trial, capturing data from 82% of surviving original enrollees.
• At the decade mark, over 80% of patients had achieved clinical remission, with radiographic progression described as limited.

Most rheumatoid arthritis (RA) patients who began with a stringent treat-to-target strategy in a clinical trial remained in remission a decade later, with only modest radiographic progression, researchers reported.

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

The median change in the modified van der Heijde-Sharp score for radiographic damage was just 2.0 points (IQR 0.5–4.5). Given a baseline average of 0.5 and a maximum possible score of 448, the authors characterized this progression as “limited” in their report published in Annals of the Rheumatic Diseases.

The investigators wrote that these findings “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 rheumatoid arthritis. Under this strategy, drug doses are adjusted to meet clinical benchmarks such as remission, constrained only by tolerability, rather than strictly following manufacturer dosage guidelines. While numerous studies confirm that TTT improves short- and medium-term outcomes, outcomes after a decade or longer remain under investigation. A 2024 study reported positive outcomes up to 20 years after initiating early TTT, though it involved participants from two separate Dutch trials using different TTT strategies.

The current study followed participants in the Norwegian ARCTIC trial, with initial results reported in 2016. The trial enrolled 230 patients randomized to two similar TTT strategies: both targeted clinical remission, but one also required completely negative ultrasound findings for joint inflammation. Ultimately, the ultrasound-guided, super-stringent approach offered no significant advantage over conventional TTT.

Accordingly, Nordberg and colleagues included all ARCTIC participants in the 10-year follow-up. Twelve patients died during that period—roughly in line with general population expectations—leaving 218 eligible for re-examination. Because 39 were unable or unwilling to participate, 179 ultimately provided 10-year outcome data.

In both the original trial and follow-up, remission was defined as a Disease Activity Score (DAS) below 1.6. This index incorporates a 44-joint swelling assessment, erythrocyte sedimentation rate, Ritchie Articular Index scores for tender joints, and the patient’s global assessment on a 100-point scale.

Mean DAS at the original ARCTIC baseline was 3.4, dropping to 1.2 by year 2 and averaging 1.1 at year 10. At both the two- and ten-year marks, approximately 80% of patients showed no Doppler signal in any joint.

One factor separated better responders from worse ones. Patients who achieved clinical remission (DAS <1.6) at year 2 were significantly more likely to maintain that status at year 10 (89.9%) than those with weaker short-term outcomes (73.1%, P=0.01). Other measures—including the conventional 28-joint DAS, ultrasound findings, ACR/EULAR 2.0 remission criteria, and systemic inflammation markers—all showed significantly higher disease activity at year 10, though still generally low, among patients who had not reached remission by year 2.

Notably, most patients remained on active treatment after 10 years, although 15% had discontinued all disease-modifying anti-rheumatic drugs (DMARDs). Roughly 44% used a single conventional DMARD, almost always methotrexate; 35% took a biologic or other targeted agent; and a small number used multiple conventional DMARDs. Sixteen patients were taking prednisolone at a mean dose of 6.2 mg/day.

An important limitation is that patients managed their own care between years 2 and 10, and the treatments they received during that interval may have influenced the results. ARCTIC lacked a non-TTT control group for comparison. Additionally, some patients participated in a substudy examining biologic withdrawal after remission, and their 10-year outcomes were included in this analysis.

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