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THU0072 A Novel Dose Reduction Therapy Using Biological Disease-Modifying Anti-Rheumatic Drugs To Target Matrix Metalloproteinase 3 Normalization Together with A Simplified Disease Activity Index ≤3.3 Yields Effects Non-Inferior To Standard Care in Rheumatoid Arthritis with Regards Maintaining Remission
  1. Y. Urata1,
  2. S. Abe2,
  3. B. Devers2,
  4. Y. Nakamura3,
  5. H. Takemoto4,
  6. K.-I. Furukawa5
  1. 1Department of Rheumatology, Tsugaru General Hospital, United Municipalities of Tsugaru, Gosyogawara
  2. 2Marketing Department, Diagnostics Division, Sekisui Medical Co., Ltd, Tokyo
  3. 3Department of Orthopedic Surgery, Tsugaru General Hospital, United Municipalities of Tsugaru
  4. 4Department of Dermatology, Tsugaru General Hospital, United Municipalities of Tsugaru, Gosyogawara
  5. 5Department of Pharmacology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

Abstract

Background While there have been previous studies into reduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) patients in clinical remission or with low disease activity, there have been no strategy studies which demonstrated non-inferiority to standard care with regard to maintaining clinical remission while reducing bDMARDs.

Objectives To evaluate whether a therapy strategy using reduced doses of bDMARDs [bDMARDs: etanercept (ETN); tocilizumab (TCZ); abatacept (ABT)] achieving both a simplified disease activity index (SDAI) score of less than 3.3 and normalization of matrix metalloproteinase (MMP) 3 levels is non-inferior in maintaining disease control in patients with RA compared with standard care (rT-4 study).

Methods 223 RA patients demonstrating both SDAI remission and MMP-3 normalization using bDMARDs for ≥3months were randomly allocated to one of four strategy groups: Standard care (SC group; n=56); SDAI-driven therapy (S group; n=54); MMP-3-driven therapy (M group; n=57); or both SDAI and MMP-3-driven therapy group (Twin; T group; n=56). Method of dose reduction (every 3 months): ETN - period between injections increased by one week; TCZ - dose reduced by 80mg or period between injections increased by one week; ABT - dose reduction by 250 mg or period between injections increased by one week; up to a minimum dose of: ETN - 25 mg every 5 weeks; TCZ - 80 mg every 5 weeks or 162 mg every 5 weeks; ABT - 250 mg every 5 weeks or 125 mg every 5 weeks. The dose was reversed to the previous level in the event that the target scores were exceeded, and the lower dose was eventually reattempted after the target was re-achieved. The primary outcome was the difference in the proportion of patients who maintained remission at 12 months among the four groups, compared against a non-inferiority margin of 10%. Secondary outcomes included functional and radiographic progression.

Results Patient characteristic demographics are summarized in Table 1. One hundred ninety-three patients completed the observation period of 12 months and three patients dropped out. Consequently, one hundred ninety-six patients were analyzed (non responder imputation). There was no difference for the rate of reduction dose of bDMARDs at 12 months in S group, M group, and T group: 37.8, 42.3 and 42.9%, respectively (p=0.4176). The M and T groups were non-inferior to the SC group (proportion of patients who maintained remission during the 12 months: 32.7% and 40.0% v 38.2%; a variation of -1.8% and 5.5%, respectively; with 95% CIs of 3.8% to 5.3% and -1.9% to 5.3%, respectively). At month 12, functional status and radiographic progression did not differ between the SC and T groups.

Conclusions Results of the rT-4 study reveal that a twin target strategy can achieve effects non-inferior to standard care with regard to maintaining clinical remission.

Disclosure of Interest None declared

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