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Research ArticleAccepted Article

Current smoking negatively affects the response to methotrexate in RA in a dose-responsive way, independently of concomitant prednisone use

Mary Safy-Khan, Maria J.H. de Hair, Paco M.J. Welsing, Jacob M. van Laar and Johannes W.G. Jacobs on behalf of the Society for Rheumatology research Utrecht (SRU)
The Journal of Rheumatology February 2021, jrheum.200213; DOI: https://doi.org/10.3899/jrheum.200213
Mary Safy-Khan
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands 2 Novartis Pharma BV, the Netherlands. Conflict of interest: JMvL received honoraria from MSD, Roche, Pfizer, BMS, Eli Lilly. MS-K was supported by a research grant from Astra Zeneca. Astra Zeneca was not involved in this study. MJHdH is an employee of Novartis Pharma BV; Novartis was not involved in this study. JWGJ and PMJW did not report competing interests. Corresponding author: M. Safy-Khan. Postal address: Department of Rheumatology & Clinical Immunology, G02.228, University Medical Center Utrecht, Box 85500, 3508 GA, Utrecht, the Netherlands. Email: marysafy@hotmail.com
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Maria J.H. de Hair
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands 2 Novartis Pharma BV, the Netherlands. Conflict of interest: JMvL received honoraria from MSD, Roche, Pfizer, BMS, Eli Lilly. MS-K was supported by a research grant from Astra Zeneca. Astra Zeneca was not involved in this study. MJHdH is an employee of Novartis Pharma BV; Novartis was not involved in this study. JWGJ and PMJW did not report competing interests. Corresponding author: M. Safy-Khan. Postal address: Department of Rheumatology & Clinical Immunology, G02.228, University Medical Center Utrecht, Box 85500, 3508 GA, Utrecht, the Netherlands. Email: marysafy@hotmail.com
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Paco M.J. Welsing
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands 2 Novartis Pharma BV, the Netherlands. Conflict of interest: JMvL received honoraria from MSD, Roche, Pfizer, BMS, Eli Lilly. MS-K was supported by a research grant from Astra Zeneca. Astra Zeneca was not involved in this study. MJHdH is an employee of Novartis Pharma BV; Novartis was not involved in this study. JWGJ and PMJW did not report competing interests. Corresponding author: M. Safy-Khan. Postal address: Department of Rheumatology & Clinical Immunology, G02.228, University Medical Center Utrecht, Box 85500, 3508 GA, Utrecht, the Netherlands. Email: marysafy@hotmail.com
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Jacob M. van Laar
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands 2 Novartis Pharma BV, the Netherlands. Conflict of interest: JMvL received honoraria from MSD, Roche, Pfizer, BMS, Eli Lilly. MS-K was supported by a research grant from Astra Zeneca. Astra Zeneca was not involved in this study. MJHdH is an employee of Novartis Pharma BV; Novartis was not involved in this study. JWGJ and PMJW did not report competing interests. Corresponding author: M. Safy-Khan. Postal address: Department of Rheumatology & Clinical Immunology, G02.228, University Medical Center Utrecht, Box 85500, 3508 GA, Utrecht, the Netherlands. Email: marysafy@hotmail.com
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Johannes W.G. Jacobs
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, the Netherlands 2 Novartis Pharma BV, the Netherlands. Conflict of interest: JMvL received honoraria from MSD, Roche, Pfizer, BMS, Eli Lilly. MS-K was supported by a research grant from Astra Zeneca. Astra Zeneca was not involved in this study. MJHdH is an employee of Novartis Pharma BV; Novartis was not involved in this study. JWGJ and PMJW did not report competing interests. Corresponding author: M. Safy-Khan. Postal address: Department of Rheumatology & Clinical Immunology, G02.228, University Medical Center Utrecht, Box 85500, 3508 GA, Utrecht, the Netherlands. Email: marysafy@hotmail.com
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Abstract

Objective Current smoking reduces clinical response to several disease-modifying antirheumatic drugs (DMARDs). It is unknown if this is also the case for prednisone. We aimed to determine whether current smoking affects the clinical response to concomitant prednisone in a methotrexate (MTX)-based treatment strategy.

Methods In the CAMERA-II trial, early rheumatoid arthritis (RA) patients initiated an MTX-based strategy and were randomized to concomitant prednisone (MTX+pred) or placebo (MTX+plac) for 24 months. Linear mixed modelling was performed with disease activity score assessing 28 joints (DAS28) as dependent variable and strategy group and current smoking status as independent variables, correcting for relevant covariates. The interaction between current smoking and strategy was tested to find out whether the impact of current smoking on clinical response was different between the strategy groups with prednisone or placebo.

Results Current smoking was significantly associated with higher DAS28 over time (mean difference with non-smokers 0.57 (95% confidence interval 0.22 to 0.92), p<0.01). This association was not different between the strategy groups with prednisone or placebo (p=0.73). This negative effect of current smoking on DAS28 was dose dependent.

Conclusion Current smoking in early RA patients significantly reduces the clinical effect of an MTX-based strategy, independent of whether concomitant prednisone is used or not. This effect is dose dependent.

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The Journal of Rheumatology: 52 (7)
The Journal of Rheumatology
Vol. 52, Issue 7
1 Jul 2025
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Accepted manuscript
Current smoking negatively affects the response to methotrexate in RA in a dose-responsive way, independently of concomitant prednisone use
Mary Safy-Khan, Maria J.H. de Hair, Paco M.J. Welsing, Jacob M. van Laar, Johannes W.G. Jacobs
The Journal of Rheumatology Feb 2021, jrheum.200213; DOI: 10.3899/jrheum.200213

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Accepted manuscript
Current smoking negatively affects the response to methotrexate in RA in a dose-responsive way, independently of concomitant prednisone use
Mary Safy-Khan, Maria J.H. de Hair, Paco M.J. Welsing, Jacob M. van Laar, Johannes W.G. Jacobs
The Journal of Rheumatology Feb 2021, jrheum.200213; DOI: 10.3899/jrheum.200213
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