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  • Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis

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Rheumatoid arthritis
Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis
  1. Joshua F Baker1,2,
  2. James R ODell3,
  3. Bryant R England4,5,
  4. Jon T Giles6,
  5. Jefferey A Newcomb7,
  6. Michael D George1,
  7. Geoffrey Thiele8,9,
  8. Larry Moreland10,
  9. S Louis Bridges11,
  10. Jeffrey R Curtis12,
  11. Ted R Mikuls7
  1. 1 University of Pennsylvania, Philadelphia, Pennsylvania, USA
  2. 2 Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  3. 3 University of Nebraska Medical Center, Omaha, Nebraska, USA
  4. 4 Rheumatology, University of Nebraska Medical Center, Omaha, Nebraska, USA
  5. 5 Rheumatology, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
  6. 6 Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA
  7. 7 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
  8. 8 Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
  9. 9 Research Services, 151, Omaha VA Medical Center, Omaha, Nebraska, USA
  10. 10 Orthopedics, University of Colorado, Denver, Colorado, USA
  11. 11 Hospital for Special Surgery, New York, NY, USA
  12. 12 University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, USA
  1. Correspondence to Dr Joshua F Baker, University of Pennsylvania, Philadelphia, USA; joshua.baker{at}pennmedicine.upenn.edu

Abstract

Purpose To determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate response.

Methods This is a secondary analysis of the Rheumatoid Arthritis Comparison of Active Treatments (RACAT) trial and the (TEAR) trial. Both studies compared treatment strategies starting with conventional disease-modifying anti-rheumatic drugs (DMARDs) (triple therapy) versus etanercept plus methotrexate. We compared response rates between TNFi and triple therapy among patients with different BMI. Adipokines were measured at enrolment and associations with treatment response were examined using regression, adjusting for age, sex, BMI and baseline disease activity.

Results In RACAT (n=306), participants who were normal/underweight were more likely to benefit from TNFi versus triple therapy, with greater change in Disease Activity Score in 28 and greater ACR20 response (ACR 20: 64% vs 23%, p=0.001). In contrast, overweight/obese participants had similar response to TNFi versus triple therapy (p-for-interaction=0.001). Similarly, but modest patterns were observed in TEAR (n=601; ACR20: 67% vs 52%, p=0.05). In RACAT, adipokine scores consistent with lower adiposity also predicted greater response to TNFi (ACR20: 58% vs 37%, p=0.01) with better model fit compared with BMI alone.

Conclusions Lower BMI and evidence of lower adiposity based on adipokine profiles were associated with a superior response to TNFi compared with triple therapy. There was no difference between treatments among overweight/obese participants. The results support TNFi being a particularly important therapeutic among normal/underweight patients, with implications for clinical decisions and trial design.

  • Rheumatoid Arthritis
  • Disease Activity
  • Tumor Necrosis Factor Inhibitors

Data availability statement

Data may be obtained from a third party and are not publicly available. Sharing of limited datasets would require multiple data use agreements as well as the approval of multiple VA and non-VA Institutional Review Boards.

https://doi.org/10.1136/ard-2023-225014

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    Data availability statement

    Data may be obtained from a third party and are not publicly available. Sharing of limited datasets would require multiple data use agreements as well as the approval of multiple VA and non-VA Institutional Review Boards.

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors JFB devised the project, the main conceptual ideas and proof outline, performed statistical analysis, interpreted the results and wrote the initial draft. JFB serves as guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled. the decision to publish. JRO, TRM, and JTG provided input in study design, collection of data, reviewing and interpreting analyses and reviewing and editing the manuscript. GT was involved in performing laboratory testing, reviewing and interpreting results, and reviewing and editing the manuscript. BRE, MDG, LM, SLB, JAN and JRC were involved in review of analyses, interpretation, and reviewing/editing the final manuscript. All authors provided approval of the final manuscript.

    • Funding This work was supported by a Veterans Affairs VA Merit Award (I01 CX001703). Dr. Baker is also supported by a Rehabilitation Research & Development Merit Award (I01 CX003644). BRE is supported by the VA CSR&D (IK2 CX002203). TRM is supported by the VA BLRD (BX004660), Department of Defense (PR200793) and National Institutes of General Medical Sciences (U54 GM115458). Dr. Curtis is supported by NIAMS P30 AR072583.

    • Competing interests JFB has received consulting fees from Bristol-Myers Squibb, Pfizer, Cumberland Pharma, and CorEvitas. BRE has received research support and consulting fees from Boehringer-Ingelheim. TRM has received consulting fees from Pfizer, Horizon Therapeutics, and Gilead and has received research support from Bristol-Myers Squibb and Horizon Therapeutics.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.