SAT0202 Concomitant Methotrexate and Tacrolimus Augment the Clinical Response to Abatacept in Patients with Rheumatoid Arthritis with a Prior History of Biological Dmard Use
Authors: N. Takahashi, T. Kojima, K. Funahashi, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Abatacept (ABT) is a new class of biologic agents for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86. It has been reported that ABT was less effective in the patients with previous biological DMARDs and concomitant MTX had only little enhancing effect on ABT efficacy [1]. Tacrolimus (TAC) was approved in Japan and some other countries for the treatment of RA (oral dosage of ≤3 mg/day) [2]. It down-regulates the synthesis of inflammatory cytokines activated by T cells mainly via inhibition of a calcineurin. <h3>Objectives</h3> In this study, we investigated whether concomitant TAC had enhancing effect on ABT efficacy in the patients with previous biological DMARDs, using data from a Japanese multicenter registry system (TBCR). <h3>Methods</h3> The present study included consecutive patients with previous biological DMARDs treatment history, treated with intravenous ABT, and prospectively observed for longer than 52 weeks at TBCR-affiliated institutes (n=121). Demographic data and the following parameters of disease activity were collected; tender joint count (TJC) and swollen joint count (SJC), patient global assessment (VAS), ESR, and serum CRP at baseline, 4, 12, 24, and 52 weeks. We compared these clinical data between the patients treated without concomitant MTX or TAC (ABT-mono, n=42), those treated with concomitant MTX (ABT-MTX, n=56), and those treated with concomitant TAC (ABT-TAC, n=18). The patients treated with both MTX and TAC were excluded from this study. The last observation carried forward (LOCF) method was used in each analysis. <h3>Results</h3> In the baseline characteristic data, the ABT-mono group had higher pulmonary comorbidity rate (23.8%, p=0.030) compared to the ABT-MTX (5.4%) and ABT-TAC (16.7%) group while no other clinical parameters showed significant difference, including all disease activity indices such as DAS28-ESR (5.10, 5.30, and 5.30, p=0.949). The ABT-TAC group demonstrated significantly greater percent change (Δ%) in DAS28 score compared to the ABT-mono group while there was no significant difference between the ABT-mono and ABT-MTX group (Fig. A-1, 2). Within the ABT-TAC group, the patients taking 3 mg/day dosage of TAC demonstrated apparently greater percent change in DAS28 score compared to those taking &lt;3 mg/day (Fig. B). Although the Kaplan-Meier analysis demonstrated that the ABT-MTX group had a higher proportion of patients who discontinued due to adverse events (8.9%) compared to ABT-mono (2.4%) and ABT-TAC (0.0%) groups, the differences were not significant (p=0.227) (Fig. C). <h3>Conclusions</h3> We clearly demonstrated that concomitant TAC treatment had dose-dependent enhancing effect on the ABT efficacy, while there seemed to be little combinational effect of ABT and MTX. Since both ABT and TAC are the agents targeting T cells, there is concern regarding safety issue when used in combination. However, the discontinuation rate due to AEs in the ABT-TAC group was similar to that in the ABT-mono group. Our results demonstrate both the efficacy and safety of concomitant MTX and TAC. In particular, concomitant TAC appeared to be optimal when used in combination with ABT in patients with RA with a prior history of biological DMARD use. <h3>References</h3> Takahashi N, et al. Mod Rheumatol 2013;23:904. Takeuchi T, et al. Mod Rheumatol 2014;24:8. <h3>Disclosure of Interest</h3> N. Takahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., T. Kojima Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., K. Funahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan