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Treating to target matrix metalloproteinase 3 normalisation together with disease activity score below 2.6 yields better effects than each alone in rheumatoid arthritis patients: T-4 Study
  1. Yukitomo Urata1,
  2. Ryoko Uesato2,
  3. Dai Tanaka2,
  4. Yoshihide Nakamura3,
  5. Shigeru Motomura4
  1. 1Department of Rheumatology, Seihoku Chuo Hospital, Gosyogawara, Japan
  2. 2Department of Orthopaedic Surgery, Seihoku Chuo Hospital, Gosyogawara, Japan
  3. 3Departments of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
  4. 4Department of Pharmacology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
  1. Correspondence to Yukitomo Urata, Department of Rheumatology, Seihoku Chuo Hospital, 41 Nunoyacho, Gosyogawara 037-0053, Japan; yurata{at}


Objectives To assess whether therapy to achieve both a disease activity score in 28 joints (DAS28) less than 2.6 and matrix metalloproteinase (MMP) 3 normalisation offers better outcomes than either target alone in early rheumatoid arthritis (RA) at 56 weeks: Treating to Twin Targets (T-4) Study.

Methods 243 early RA patients were randomly allocated to one of four strategy groups: routine care (R group; n=62); DAS28-driven therapy (D group; n=60); MMP-3-driven therapy (M group; n=60); or both DAS28 and MMP-3-driven therapy group (twin; T group; n=61). Medication was started with sulfasalazine (1 g/day) in all intervention groups. Targets were DAS28 less than 2.6 for the D group, MMP-3 normalisation for the M group and both DAS28 less than 2.6 and MMP-3 normalisation for the T group. If the value in question did not fall below the previously measured level, medication was intensified, including methotrexate, other disease-modifying antirheumatic drugs and biological agents. Primary, secondary and outcome measures consisted of the proportions of patients showing clinical remission (DAS28 <2.6), radiographic non-progression (Δmodified total Sharp score ≤0.5), normal physical function (modified health assessment questionnaire score 0), or comprehensive disease remission defined as the combination of clinical remission, radiographic non-progression and normal physical function.

Results Clinical remission at 56 weeks was achieved by more patients in the T group (56%) than in the R group (p<0.0005) or M group (p<0.0005).

Conclusions Results of the T-4 Study reveal that a twin target strategy can achieve a high clinical remission rate in early RA.

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study protocol was approved by the institutional review committee at each participating centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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