Success with Treat-to-Target Therapy in Rheumatoid Arthritis Lasts Up to Two Decades: Study

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The study that followed participants in two of the first clinical trials to test the strategy revealed that success with "treat-to-target" therapy for early-stage RA lasted up to 2 years. The trials aimed at drug-free remission in one, low disease activity in the other

"The majority of patients in the trials had maintained the benefits when examined again after 7-10 following the trial's ending, which was 12-20 years after starting treatment," the researchers reported.

"In the follow-up exams, 91% of these patients had low disease activity (Disease Activity Score [DAS] <2.4), and 68% were in remission (DAS <1.6)."

Sascha L Heckert, Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands, and colleagues conducted the study to assess disease outcomes after 20 and 12 years of patients with rheumatoid or undifferentiated arthritis (UA), treated-to-target in the BeSt and IMPROVED trials.

In the IMPROVED trial (inclusion from 2007-2010, duration five years), 610 patients with early RA/UA started methotrexate (MTX with prednisone bridging. The treatment target was remission (DAS < 1.6). Patients not in early remission were randomized to 1. cs disease-modifying antirheumatic drug (csDMARD) combination therapy or 2. bDMARD/csDMARD combination therapy.

In the BeSt trial (inclusion 2000–2002, duration ten years), 508 patients with early rheumatoid arthritis were randomized to: (a) sequential monotherapy, (b) step-up combination therapy, (c) initial csDMARD combination therapy, (d) initial bDMARD/csDMARD combination therapy. The treatment target was low disease activity (DAS ≤ 2.4).

These patients were invited for long-term follow-up between 2019–2022.

In the follow-up study, one-hundred-fifty-three ex-Best and 282 ex-IMPROVED patients participated after a median of 12 and 20 years since the study started.

The study led to the following findings:

  • In ex-BeSt and ex-IMPROVED patients, the rate of low disease activity was 91%, and 68% were in DAS remission.
  • Median SHS was 14.0 in ex-BeSt (IQR 6.0–32.5; progression since end BeSt 6.0, IQR 2.0–12.5) and 8 in ex-IMPROVED participants (IQR 3–16; progression since end IMPROVED 4, IQR 2–9).
  • Mean HAQ was 0.8 ± 0.6 in ex-BeSt (change since end BeSt: 0.3 ± 0.5) and 0.6 ± 0.6 in ex-IMPROVED participants (change since end IMPROVED: 0.06 ± 0.5).

In conclusion, At 12/20 years after the treatment initiation, most rheumatoid arthritis and undifferentiated arthritis who had been treated to target low DAS or DAS remission were in DAS remission and had limited functional disability.

Radiographic damage progression was mild, although not suppressed completely.


Heckert, S. L., Maassen, J. M., Nevins, I., Baudoin, P., M, G., Huizinga, T. W., Bergstra, S. A., & Allaart, C. F. Long-term clinical outcomes in early rheumatoid arthritis that was treated-to-target in the BeSt and IMPROVED studies. Rheumatology.

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