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Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis

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A Correction to this article was published on 27 January 2022

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Abstract

Objectives

Janus kinase (JAK) inhibitors are a new class of medication for treatment of rheumatoid arthritis (RA), and such inhibitors alter levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in RA patients. However, the extent of such changes has not been systematically reviewed.

Method

A systematic review and network meta-analysis was performed on randomized trials in RA patients in response to JAKi identified from Pubmed, Medline, Embase, and Cochrane Controlled Trials Register. The primary outcome was mean change of HDL-C and LDL-C from baseline. Mean treatment differences and the rank of the effect of various JAKi on HDL-C and LDL-C were estimated.

Results

Based on data from 18 unique studies involving five approved JAK inhibitors and 6697 RA patients (JAKi = 3341, placebo = 3356), such inhibitors led to a mean increase of 8.11 mg/dl (95% CI 6.65–9.58, I2 = 82%) in HDL levels from baseline, and a mean increase of 11.37 mg/dl (95% CI 7.84–14.91, I2 = 88%) in LDL levels from baseline. Cardiovascular disease risk did not differ significantly between patients who received JAK inhibitors or those who received placebo or active agents.

Conclusions

Our analysis suggests that, at their recommended doses, all five JAK inhibitors lead to an increase in HDL and LDL levels in RA patients. Further long-term research is required to extend these results and understand whether changes in lipid levels in RA patients can affect cardiovascular risk.

Key Points

• This is the first systematic review and NMA examining the effect of all five clinically approved JAK inhibitors on lipid levels in RA patients.

• Recommended doses of JAK inhibitors used for the treatment of RA patients can induce a significant increase in HDL and LDL levels.

• Indirect pairwise comparisons suggest that only upadacitinib and peficitinib have significantly different ability to induce LDL change in RA patients.

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Data availability

The data that support the findings of this study and soft code are available in corresponding author.

Change history

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Acknowledgements

This work was supported by the National Science and Technology Major Project (2017ZX09304023).

Funding

This study was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (2017ZX09304023).

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Authors and Affiliations

  1. National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Institute of Clinical Trial Center, West China Hospital, Sichuan University, Sichuan, 610041, Chengdu, China

    Na Li, Zhong-Ping Gou, Shuang-Qing Du, Xiao-Hong Zhu, Xiu-Fang Liang, Yong-Sheng Wang & Ping Feng

  2. Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

    Hui Lin

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  1. Na Li
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Correspondence to Ping Feng.

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Na Li and Zhong-Ping Gou contributed equally and should be considered co-first authors

The original online version of this article was revised due to the following errors: in the first affiliation details were incorrectly given as 'Clinical Trials' but should have been 'Clinical Trial Center'; In the Results section under Study characteristics, the total data should have been 906 instead of 806 and 570 instead of 488; the Tables 2, 3 and Figure 4 were not presented correctly and has been corrected.

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Li, N., Gou, ZP., Du, SQ. et al. Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis. Clin Rheumatol 41, 677–688 (2022). https://doi.org/10.1007/s10067-021-06003-z

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