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. 2025 May;10(5):551-563.
doi: 10.1016/j.jacbts.2024.11.010. Epub 2025 Feb 5.

IL-6 Inhibitors and TNF Inhibitors: Impact on Exercise-induced Cardiac Adaptations in Patients With Rheumatoid Arthritis

Simon Jønck  1 , Malte Lund Adamsen  2 , Iben E Rasmussen  3 , Anna A Lytzen  3 , Mathilde Løk  4 , Morten Asp Vonsild Lund  4 , Lene Dreyer  5 , Peter G Jørgensen  6 , Niels Vejlstrup  7 , Lars Køber  7 , Robin Christensen  8 , Søren Jacobsen  9 , Bente Klarlund Pedersen  3 , Helga Ellingsgaard  3 , Pil Højgaard  10 , Ronan M G Berg  11 , Regitse Højgaard Christensen  12
Affiliations

IL-6 Inhibitors and TNF Inhibitors: Impact on Exercise-induced Cardiac Adaptations in Patients With Rheumatoid Arthritis

Simon Jønck et al. JACC Basic Transl Sci. 2025 May.

Abstract

Interleukin-6 inhibitors (IL-6i) are commonly used in patients with rheumatoid arthritis to reduce inflammation from chronically increased IL-6. IL-6 levels increase transiently following exercise, exerting numerous positive effects. This study examined if beneficial exercise-induced cardiac adaptations were attenuated in patients with rheumatoid arthritis in concomitant IL-6i treatment compared with tumor necrosis factor inhibitors. Compared with control, we found that the tumor necrosis factor inhibitor-treated group, but not the IL-6i group, had a significant increase in left ventricular mass following 12 weeks of supervised exercise. However, the interaction effect of treatment modalities on exercise-induced cardiac adaptations was insignificant. (Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During IL-6 vs TNF Antibody Therapy; NCT05215509).

Keywords: cardiac adaptations; exercise; interleukin-6; rheumatoid arthritis.

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Conflict of interest statement

Funding Support and Author Disclosures The Centre for Physical Activity Research is supported by TrygFonden (grants ID 101390, ID 20045, and ID 125132). Dr Jønck was supported by The Danish Rheumatism Association (grants ID R224-A8298-B1963 and ID R212-A7782-B1963), The Rigshospitalet Research Grant, Gangstedfonden (grant ID A40059), King Christian the 10th Foundation, and Snedkermester Sophus Jacobsen and wife Astrid Jacobsens Foundation. Dr Adamsen was supported by the Novo Nordisk Foundation (grant ID: NNF20OC0065929), The Danish Rheumatism Association (grant ID: R202-A7503), and a Holbæk Hospitals research grant. Dr Christensen was supported by a grant from the Danish Heart Foundation (16-R107-A6704-22970) and Danish Cardiovascular Academy (CPD5Y-2021001-DCA), which is funded by the Novo Nordisk Foundation and The Danish Heart Foundation. Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital are supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Jønck is currently employed at Novo Nordisk. Dr Adamsen has received a speaking fee from Novartis. Dr Dreyer has received research grants (paid to institution) from BMS and Abbvie outside the present work; and travel expenses from Janssen, UCB, and Boehringer Ingelheim. Dr Køber has received speaker honoraria from AstraZeneca, Boehringer, Novartis, and Novo Nordisk. Dr Pedersen has received speaker honorarium from Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flowchart of Study BL = baseline; cMRI = cardiac magnetic resonance imaging; DAS28-ESR = Disease Activity Score-28 for rheumatoid arthritis with erythrocyte sedimentation rate; FU = follow-up; ITT = intention-to-treat; PP = per-protocol; RA = rheumatoid arthritis.
Figure 2
Figure 2
Structural and Functional Cardiac Outcomes (A) Change in LVM from baseline to follow-up. Individual data points are presented for each group in gray circles. The estimated least square means change with 95% CIs represented in bold circles. The interaction effect of concomitant IL-6i treatment on exercise-induced changes to LVM was found insignificant. (B) Change in LVSV from baseline to follow-up. Individual data points are presented for each group in gray circles. The estimated least square means change with 95% CIs represented in bold circles. (C) Change in LVEDV from baseline to follow-up. Individual data points are presented for each group in gray circles. The estimated least square means change with 95% CIs represented in bold circles. Ex = exercise; IL-6i = interleukin-6 inhibitor; LVEDV = left ventricular end-diastolic volume; LVM = left ventricular mass; LVSV = left ventricular stroke volume; TNFi = tumor necrosis factor inhibitor.
See this image and copyright information in PMC

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