Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan

Takeuchi, Tsutomu; Ishida, Katsuhiro; Shiraki, K; Yoshiyasu, Takashi

doi:10.1080/14397595.2017.1332471

Cited by 20 publications

(20 citation statements)

References 34 publications

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“…A majority of patients in the present study took a dose of TAC ≤ 2 mg/d, with a mean dose of 1.6 mg/d at week 24. This result is similar to that reported in the TAC PMS study (mean, 1.3 mg/d) . In patients previously treated with bDMARDs, TAC at baseline dose‐dependently augmented the efficacy of add‐on ABT, and concomitant TAC at 3 mg/d demonstrated the maximum efficacy .…”

Section: Discussionsupporting

confidence: 87%

“…That study found that elderly patients had a higher incidence of infection compared with non‐elderly patients, and that patients treated with ABT had a higher incidence of infection compared to those treated with other bDMARDs (8/99 patients: 8.1% vs 0.0%‐6.1%). However, among eight patients who experienced infection in this cohort, six were aged >70 years, and only one patient had a serious but reversible infection . Since TAC is a calcineurin inhibitor which suppresses the activation of T lymphocytes, and ABT is also an agent that inhibits T cell activation by binding to CD80/86 on the antigen‐presenting cell surface, one would expect the combined use of these agents to further increase the risk of infection.…”

Section: Discussionmentioning

confidence: 97%

“…A prospective PMS study was conducted in Japan to evaluate the safety and efficacy of add‐on TAC therapy for RA patients with inadequate response to bDMARDs . That study found that elderly patients had a higher incidence of infection compared with non‐elderly patients, and that patients treated with ABT had a higher incidence of infection compared to those treated with other bDMARDs (8/99 patients: 8.1% vs 0.0%‐6.1%).…”

Section: Discussionmentioning

confidence: 99%

“…However, in the clinical practice in Japan, the majority of patients are treated with 1 mg/d of add‐on TAC in patients treated with biologics. The initial dosage of TAC was 1.2 ± 0.5 mg/d and gradually increased to 1.3 ± 0.6 mg/d at week 24 in Japanese PMS …”

Section: Methodsmentioning

confidence: 98%

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Clinical effectiveness and safety of additional administration of tacrolimus in rheumatoid arthritis patients with an inadequate response to abatacept: A retrospective cohort study

et al. 2019

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Objective: Abatacept (ABT) demonstrates good clinical efficacy and retention in rheumatoid arthritis (RA) patients. However, no rescue treatment option against inadequate response to ABT exists. Since tacrolimus (TAC) and ABT suppress T lymphocytes via different mechanisms and a combination of these agents could potentially be effective, this study aimed to examine the efficacy and safety of add-on TAC therapy in RA patients with inadequate response to ABT. Methods:Of 550 patients treated with ABT and registered in a Japanese multicenter registry, 25 consecutive patients who underwent add-on TAC therapy and were followed for longer than 24 weeks were included in this study.Results: Mean patient age was 67.0 years, disease duration was 16.2 years, and duration of ABT treatment was 1.2 years at the initiation of add-on TAC therapy. Mean TAC dose was 1.2 mg/d at baseline and 1.6 mg/d at week 24. Mean Disease Activity Score of 28 joints -erythrocyte sedimentation rate was significantly improved at week 24 (3.35) relative to baseline (4.97). The proportion of patients who achieved low disease activity or remission was 40.0%, and the European League Against Rheumatism moderate or good response was 72.0%. ABT retention rate was 92.0% at week 24, as calculated by Kaplan-Meier analysis. Only one patient discontinued add-on TAC therapy due to an adverse event (itching sensation).Conclusion: This is the first report describing the efficacy and safety profile of addon TAC therapy with a focus on RA patients with inadequate response to ABT. Our findings suggest that add-on TAC therapy is a worthwhile complementary treatment option in daily clinical practice. K E Y W O R D Sabatacept, additional administration, inadequate response, rheumatoid arthritis, tacrolimus

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 98%

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Clinical effectiveness and safety of additional administration of tacrolimus in rheumatoid arthritis patients with an inadequate response to abatacept: A retrospective cohort study

et al. 2019

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“…Tacrolimus has been reported to be effective, and it shows an acceptable safety profile in RA patients with an inadequate response to csDMARDs, including methotrexate [6,7]. In addition, it has been suggested that add-on tacrolimus with bDMARDs may improve the clinical outcomes, even when patients show inadequate responses to bDMARDs with concomitant methotrexate [8][9][10]. These findings indicate that the use of tacrolimus may be one of the valuable options for patients with contraindications for or an inadequate response to bDMARDs and/or methotrexate.…”

Section: Introductionmentioning

confidence: 99%

Concomitant Treatment with Etanercept and Tacrolimus Synergistically Attenuates Arthritis Progression via Inhibition of Matrix Metalloproteinase-3 Production and Osteoclastogenesis in Human TNF-α Transgenic Mice

Seki¹,

Takai-Imamura²,

Kohara-Tanaka³

et al. 2019

Mediators of Inflammation

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In the present study, we investigated the effects and mechanisms of action of a combined treatment with etanercept, a soluble tumor necrosis factor receptor (p75) Fc fusion protein, and tacrolimus, a calcineurin inhibitor on the progression of arthritis in human tumor necrosis factor-α (TNF-α) transgenic (hTNF-Tg) mice. Single-drug treatments with etanercept and tacrolimus attenuated the clinical signs but not the radiographic changes associated with the development of arthritis in mice. On the contrary, combined treatment significantly suppressed the radiographic progression and also improved the clinical signs. The combined treatment exhibited synergistic effects of the two drugs in reducing the serum matrix metalloproteinase-3 level and the number of peripheral CD11bhigh osteoclast precursor cells. Moreover, tacrolimus inhibited the cytokine-induced osteoclast differentiation in synergy with etanercept in an in vitro assay. Interestingly, tacrolimus did not inhibit the production of antidrug antibodies (ADAs) against etanercept in the hTNF-Tg mice. This result implies that the synergistic effects of etanercept and tacrolimus are not due to secondary effects derived from the suppression of ADA production by tacrolimus but are due to their primary effects. These findings suggest that concomitant treatment with etanercept and tacrolimus may be one of preferable treatment options to control disease activities for patients with rheumatoid arthritis, especially for those with bone resorption.

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Retrospective investigation of tacrolimus combined with an anti‐tumor necrosis factorα antibody as remission induction therapy for refractory ulcerative colitis: Efficacy, safety, and relapse rate

et al. 2019

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Background and AimCombined therapy with tacrolimus (TAC) and an anti‐tumor necrosis factorα (TNFα) antibody is used to induce remission in ulcerative colitis (UC) patients who have not responded to monotherapy with either drug. We evaluated the efficacy and safety of combined therapy, as well as the relapse rate.MethodsCombined therapy was performed to induce remission in UC patients showing an inadequate response to monotherapy with TAC or an anti‐TNFα antibody. The following items were assessed retrospectively: (i) clinical characteristics, (ii) the remission induction rate, (iii) the relapse rate, and (iv) adverse events.ResultsCombined therapy induced remission in 7 of the 12 patients (58.3%). There were no significant differences in clinical characteristics between the patients with and without the successful induction of remission. However, the number of female patients tended to be higher in the remission group than in the nonremission group. The remission group also showed trends of a lower clinical activity index (Lichtiger index; CAI) on admission and before combined therapy and a lower total dose of prednisolone during hospitalization. The 1‐year relapse rate was 33.3%. Adverse events due to combined therapy included renal impairment (n = 2), tremors (n = 2), influenza (n = 1), and a positive cytomegalovirus antibody test (n = 3). None of these events were serious.ConclusionsCombined therapy was effective in more than half of the patients with refractory UC who had not responded to monotherapy. Our findings suggest that combination therapy may be a new, third option for the treatment of refractory UC.

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Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan

Abstract: TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

Cited by 20 publications

References 34 publications

Clinical effectiveness and safety of additional administration of tacrolimus in rheumatoid arthritis patients with an inadequate response to abatacept: A retrospective cohort study

Clinical effectiveness and safety of additional administration of tacrolimus in rheumatoid arthritis patients with an inadequate response to abatacept: A retrospective cohort study

Concomitant Treatment with Etanercept and Tacrolimus Synergistically Attenuates Arthritis Progression via Inhibition of Matrix Metalloproteinase-3 Production and Osteoclastogenesis in Human TNF-α Transgenic Mice

Retrospective investigation of tacrolimus combined with an anti‐tumor necrosis factorα antibody as remission induction therapy for refractory ulcerative colitis: Efficacy, safety, and relapse rate

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