Disease activity remained stable in later follow-up despite declining methotrexate use and dose among patients with rheumatoid arthritis managed under a treat-to-target strategy, while targeted synthetic disease-modifying antirheumatic drug use increased, according to a single-center study published in Rheumato.
The retrospective, time-observational study included 764 patients with rheumatoid arthritis (RA) who met the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria, received treat-to-target care from first consultation, and had at least 1 year of consecutive follow-up. Researchers analyzed 34,293 measurements collected between August 2010 and April 2025, with outcome periods in the results reported through July 2025.
Treatment targeted clinical remission within 6 months using disease activity indices, including the Simplified Disease Activity Index (SDAI). Researchers analyzed monthly institutional averages for SDAI, Health Assessment Questionnaire Disability Index (HAQ), and pain visual analog scale scores. Secondary outcomes included SDAI remission rate and EuroQOL-5 Dimension score.
At first consultation, the mean patient age was 63.6 years, mean disease duration was 5.8 years, mean SDAI score was 13.3, mean HAQ score was 0.49, and mean pain visual analog scale score was 35.1 mm. During follow-up, patients had a mean 45.7 consultations and were followed for a mean 69.8 months.
Researchers divided follow-up into two outcome-based periods. For SDAI and pain scores, the first period extended from August 2010 to November 2015, and the second from December 2015 to July 2025. For HAQ, the first period extended from August 2010 to November 2018, and the second from December 2018 to July 2025.
During the first SDAI period, mean SDAI score decreased from 7.35 to 3.55. Methotrexate prescription rates were relatively stable, changing from 79% to 77%, while mean methotrexate dose increased from 7.87 to 9.46 mg per week. Glucocorticoid prescribing declined from 63% to 16%, biologic disease-modifying antirheumatic drug use increased from 23% to 26%, and targeted synthetic disease-modifying antirheumatic drug use increased from 0% to 5%.
In multivariate analyses of monthly institutional trends during the first SDAI period, higher mean methotrexate dose was associated with lower mean SDAI scores, while glucocorticoid prescribing was associated with higher SDAI scores.
Functional outcomes followed a different pattern. During the first HAQ period, mean HAQ score increased from 0.35 to 0.51, while mean age increased from 66.5 to 71.5 years. Additional analyses identified baseline HAQ score, baseline pain visual analog scale score, and number of comorbidities as factors associated with HAQ score during follow-up.
During the second SDAI period, mean SDAI score remained stable, changing from 4.02 to 4.08. Methotrexate prescription rates declined from 74% to 50%, and mean methotrexate dose declined from 8.97 to 7.83 mg per week. Targeted synthetic disease-modifying antirheumatic drug use increased from 5% to 21%, with the combined prescription rate of baricitinib, upadacitinib, and filgotinib increasing from 0% to 20%.
In the second HAQ period, mean HAQ score decreased from 0.51 to 0.37. The combined prescription rate of baricitinib, upadacitinib, and filgotinib was negatively correlated with HAQ score in multivariate analysis. Across the full follow-up period, the grouped administration rate of baricitinib, upadacitinib, and filgotinib was negatively correlated with pain visual analog scale score in multivariate analysis.
Across the full study period, SDAI, HAQ, and pain visual analog scale scores decreased from baseline to the end of follow-up, while SDAI remission rate increased. EuroQOL-5 Dimension score declined over the same period. Methotrexate prescription rate, methotrexate dose, conventional synthetic disease-modifying antirheumatic drug use, and glucocorticoid use decreased, while biologic and targeted synthetic disease-modifying antirheumatic drug use increased.
The researchers reported a stronger negative correlation between age and estimated glomerular filtration rate during the second period. They noted that concerns about renal function and methotrexate-associated lymphoproliferative disease may have contributed to reduced methotrexate prescribing in later years.
The study had several limitations. It was conducted at one medical facility in a rural area in Japan and included an older cohort than other RA cohorts. The analysis was based on monthly institutional averages and was not designed to evaluate the effectiveness of individual drugs. The researchers described the study as time-observational. Educational background and economic status were not assessed.
The authors concluded that medication adjustments over time may help maintain clinical indices under a treat-to-target approach, even as patient characteristics change. However, because this was a real-world, time-observational trend analysis, the findings should be interpreted as associations and trends rather than evidence that any individual drug or drug class caused the observed improvements.
Disclosures: The researchers reported no conflicts of interest.
Source: Rheumato