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Effect and safety profile of belimumab and tacrolimus combination therapy in thirty-three patients with systemic lupus erythematosus

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Abstract

Introduction/objectives

Belimumab combined with mycophenolate mofetil has been proven to be effective for treating systemic lupus erythematosus (SLE) in several randomized controlled trials. Calcineurin inhibitors are also useful in controlling the activity of SLE. However, the safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. Therefore, the current single-center retrospective study aimed to analyze the safety/efficacy profile of belimumab-tacrolimus (B-T) combination therapy in patients with SLE.

Method

Patients with SLE administered tacrolimus and belimumab during treatment were included in the study. Samples were analyzed for the drug retention rate, SLE flare rate, infection incidence rate, and glucocorticoid-sparing effect of the B-T combination therapy.

Results

Thirty-three patients with SLE were treated with B-T combination therapy at our institution. Four patients discontinued treatment due to insufficient response or adverse events. The drug retention rate was over 90% at week 52 and approximately 80% at day 1000. Only one patient developed serious infection. The lupus low disease activity state (LLDAS) achievement ratio was 9.1% on the day of initiation and improved to 64.0% at 52 weeks after initiation. SLE flares were observed in three patients (9.1%) in the first 52 weeks after initiation, and in five patients (15.2%) throughout the study period. A glucocorticoid-reducing effect was also observed in patients treated with B-T combination therapy.

Conclusions

In most patients with SLE, B-T combination therapy is well tolerated with a good efficacy profile and glucocorticoid-reducing effect. Thus, B-T combination therapy represents a feasible option for patients with refractory lupus.

Key Points

• The safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed.

• The drug retention rate of belimumab-tacrolimus combination therapy was over 90% at week 52 and around 80% on day 1000

• Almost none of the patients suffered from severe infection after the initiation of belimumab-tacrolimus combination therapy.

• Belimumab-tacrolimus combination therapy is efficacious in suppressing lupus activity and achieving LLDAS.

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Published article and its supplementary information files include all data generated or analyzed during this study.

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Authors and Affiliations

  1. Immuno-Rheumatology Center, St. Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, Japan

    Takehiro Nakai, Sho Fukui, Genki Kidoguchi, Yukihiko Ikeda, Ayako Kitada, Atsushi Nomura, Hiromichi Tamaki, Mitsumasa Kishimoto & Masato Okada

  2. Center for Clinical Epidemiology, St. Luke’s International University, Tokyo, Japan

    Sho Fukui

  3. Department of Emergency and General Medicine, Kyorin University School of Medicine, Tokyo, Japan

    Sho Fukui

  4. Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan

    Mitsumasa Kishimoto

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Contributions

TN was involved in the conception of the study and its design, data acquisition and analysis, drafting the manuscript, and final approval.

SF was involved in data acquisition, statistical analysis, and final approval.

MO was involved in the study conception and design, drafting the manuscript, and final approval. All authors approved the final manuscript.

All authors were involved in data acquisition and revised the manuscript and approved its final version.

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Correspondence to Takehiro Nakai.

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MK has received consulting fees and/or honoraria from AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma.

MO has received speaking fees and/or honoraria from Eli Lilly and Company, Santen Pharmaceutical, Mitsubishi Tanabe Pharma, Pfizer, and Abbott Japan.

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Nakai, T., Fukui, S., Kidoguchi, G. et al. Effect and safety profile of belimumab and tacrolimus combination therapy in thirty-three patients with systemic lupus erythematosus. Clin Rheumatol 41, 3735–3745 (2022). https://doi.org/10.1007/s10067-022-06325-6

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