EARLY use of disease-modifying antirheumatic drugs in patients with recent-onset undifferentiated arthritis provided greater short-term improvements in disease activity than symptomatic treatment alone, according to new trial findings, although differences between treatment strategies were no longer evident after 12 months.
Testing Early Intervention in Undifferentiated Arthritis
Undifferentiated arthritis represents a heterogeneous condition in which some patients progress to rheumatoid arthritis while others experience spontaneous resolution. Current guidance often recommends early disease-modifying antirheumatic drugs for patients considered at risk of persistent disease, but uncertainty remains regarding which patients benefit most. Researchers therefore investigated whether early DMARD treatment offers advantages over symptomatic therapy in contemporary undifferentiated arthritis populations.
Three Treatment Strategies Compared
The Induction of Cure in Early Arthritis (I CEA) study was a multicentre, single-blinded randomised controlled trial consisting of a 3-month intervention phase followed by a 9-month observational period. Eighty-five DMARD-naïve patients with arthritis affecting at least two joints and not meeting 2010 rheumatoid arthritis classification criteria were randomised 1:1:1 to receive standard-dose non-steroidal anti-inflammatory drugs (NSAIDs; n=29), methotrexate (MTX) beginning at 15 mg/week and increasing to 25 mg/week (n=28), or baricitinib 4 mg/day (n=28). All participants also received a glucocorticoid injection. The primary outcome was improvement in Disease Activity Score (DAS 44/53 joints) at 3 months. Secondary assessments included disease activity at 12 months and safety outcomes. Overall, 123 participants completed the double-blind treatment period, representing 83.7% of enrolled patients.
Short-Term Benefits Seen with Disease-Modifying Antirheumatic Drugs
After 3 months, baricitinib demonstrated significantly greater DAS improvement than NSAIDs, with an adjusted mean difference of −0.52 (95% CI −0.93 to −0.11; p=0.01). Methotrexate showed a numerically similar benefit, with an adjusted mean difference of −0.39 (95% CI −0.84 to 0.06), although this did not reach statistical significance (p=0.09). At 12 months, mean DAS scores were 1.3 (SD 0.7) in the MTX group, 1.6 (SD 0.9) in the NSAID group, and 1.7 (SD 0.9) in the baricitinib group, with no significant differences between groups (p=0.38). Severe adverse event rates remained low across all treatment arms.
Individualising Future Treatment Decisions
These findings suggest disease-modifying antirheumatic drugs may accelerate symptom improvement in early undifferentiated arthritis, particularly with baricitinib. However, favourable long-term outcomes across all groups highlight the importance of balancing potential benefits against treatment risks and tailoring therapy to individual patient needs and preferences.
Reference
Nevins IS et al. Induction of Cure in Early Arthritis (I CEA): results of a randomised clinical trial to compare three treatment strategies in recent onset undifferentiated arthritis. RMD Open. 2026;12:e006828.
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