OP0104 Tocilizumab: dose reduction or interval spacing – which proves a better tapering strategy for rheumatoid arthritis in clinical remission?
Authors: Y Urata, S Abe, B Devers, Y Nakamura, H Takemoto, K-I Furukawa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A number of studies have revealed that reduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) is possible for some rheumatoid arthritis (RA) patients in whom bDMARD treatment has induced clinical remission or low disease activity. For tocilizumab (TCZ), while there have been studies concerning tapering, there have been no studies regarding which tapering option is better in RA after clinical remission has been achieved: a dose reduction strategy (DRS) or an interval spacing strategy (ISS). We previously demonstrated that a twin target strategy [targeting both a simplified disease activity index (SDAI) score of less than 3.3 and normalization of matrix metalloproteinase (MMP) 3 levels] can achieve effects non-inferior to standard care with regard to maintaining clinical remission in the rT-4study. <h3>Objectives</h3> To evaluate any significant differences that may be present between the two strategies (DRS and ISS) while tapering TCZ in RA patients who satisfied the SDAI remission and MMP-3 normalization targets under the twin target scheme. <h3>Methods</h3> DRS was used in patients treated with intravenous (IV) TCZ, whereas ISS was used for those treated by subcutaneous injection (SC). 57 RA patients who demonstrated SDAI remission and MMP-3 normalization using TCZ (IV, n=42; SC, n=15) participated. Dose reduction methodology (every 3 months): DRS- dose reduced by 80mg; ISS- period between injections increased by one week; up to a minimum dose of: DRS- 80 mg every 4 weeks; ISS-162 mg every 6 weeks. The dose was reverted 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 number of the times when a patient9s SDAI exceeded 3.3 across the four time points. <h3>Results</h3> Fifty-five patients completed the observation period of 12 months and were analyzed (ITT). There were differences in the number of the times which SDAI scores exceed the target over the 12 months in the DRS group vs the ISS group: 2.4±1.7 and 0.9±1.2, respectively (p=0.0027). DRS had a duration (months) of maintained SDAI remission significantly shorter than that of ISS (3.9±5.0 vs 7.4±5.1, p=0.0213). At month 12, the proportions for DRS and ISS, respectively, for ΔmTTS≤0.5 were 71.4 and 66.7% (p=0.7293); for maintained HAQDI=0 were 83.3 and 66.7 (p=0.4227) and for AE were 81.0 and 46.7 (p=0.0112). The total dose for TCZ in DRS tended to be lower than that for ISS (1367±840vs 1626±583mg, p=0.0824). The rate of total TCZ reduction showed a significant difference between DRS and ISS (29.3±15.2% vs41.8±15.0%, p=0.0037). Comparing three groups consisting of 400mg&lt;, 401$&lt;&lt;$500mg and 500mg&lt; across the DRS with ISS groups, there were significantly greater number of times when SDAI exceeded 3.3 in the DRS vs the ISS group; 2.3±1.6, 2.7±1.8 and 2.4±1.9, p=0.0395. <h3>Conclusions</h3> ISS using the twin targets as defined by the rT-4 study is an excellent strategy that is both safe and cost-effective for RA patients who are both being treated with TCZ and have reached said targets. <h3>Disclosure of Interest</h3> None declared