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Effects of DMARD and Anti-TNF Therapies on Inflammatory Markers, Lipid Profile, and Insulin Resistance in Rheumatoid Arthritis: A Controlled Study

Year 2026, Volume: 16 Issue: 1, 32 - 36, 31.01.2026
https://doi.org/10.16899/jcm.1808008

Abstract

Aim
This study aimed to compare the effects of disease-modifying antirheumatic drugs (DMARDs) and anti-tumor necrosis factor (anti-TNF) therapy on inflammatory markers, lipid profile, and insulin resistance in rheumatoid arthritis (RA) patients, and to evaluate the potential cardiovascular impact of biological treatments.
Material and Method
This single-center, prospective study included 122 participants between May 2012 and May 2013: 35 RA patients treated with DMARDs, 31 RA patients treated with anti-TNF agents, and 56 healthy controls. Inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF)], lipid profile [total cholesterol, triglycerides, high-density lipoprotein (HDL), atherogenic index of plasma (AIP)], and glycemic parameters [fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR)] were assessed.
Results
ESR and CRP levels were significantly higher in RA groups compared with controls (p<0.001), and CRP was higher in the anti-TNF group than in the DMARD group. RF positivity was markedly increased in RA patients (p<0.001). No significant differences were found among groups for lipid profile or AIP (p>0.05). Insulin and fasting glucose levels were similar, while HOMA-IR was higher in controls and marginally lower in RA groups (p=0.049).
Conclusion
RA patients exhibited significantly elevated inflammation, whereas lipid profile and AIP did not differ between treatment groups. Suppression of inflammation was associated with partial improvement in insulin resistance. Cardiometabolic risk in RA should be assessed by considering not only conventional lipid parameters but also inflammation and insulin resistance as multifactorial determinants.

Ethical Statement

The study was carried out with the permission of the Clinical Research Ethics Committee of Haydarpaşa Numune Training and Research Hospital (Approval No: 2012/8).

References

  • 1. Firestein GS, Kelley WN. Kelley and Firestein's Textbook of Rheumatology. 11th ed. Philadelphia: Elsevier; 2021.
  • 2. Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360-72.
  • 3. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130-6.
  • 4. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328-37.
  • 5. Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003;62(8):722-7.
  • 6. Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59(12):1690-7.
  • 7. Myasoedova E, Crowson CS, Kremers HM, Roger VL, Fitz-Gibbon PL, Therneau TM, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70(3):482-7.
  • 8. Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum. 2018;48(1):22-7.
  • 9. Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-99.
  • 10. European Alliance of Associations for Rheumatology (EULAR). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2022;81(6):787-99.
  • 11. Peters MJL, Symmons DPM, McCarey D, Dijkmans BAC, Nicola P, Kvien TK, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2019;79(6):768-76.
  • 12. Macáková K, Zavada J, Jebavý L, Šenolt L. Metabolic effects of anti-TNF-α treatment in rheumatoid arthritis. Diseases. 2023;11(4):164.
  • 13. Van den Oever IAM, Raterman HG, Nurmohamed MT, Simsek S. The effect of anti-TNF treatment on body composition and insulin resistance in rheumatoid arthritis patients. Rheumatol Ther. 2021;7(1):201-11.
  • 14. Ceccarelli F, Massafra U, Perricone C, Idolazzi L, Giacomelli R, Tirri R, et al. Anti-TNF treatment response in rheumatoid arthritis patients with moderate disease activity: a prospective observational multicentre study (MODERATE). Clin Exp Rheumatol. 2017;35(1):24-32.
  • 15. Drosos AA, Venetsanopoulou AA, Pelechas E, Voulgari PV. Exploring cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Eur J Intern Med. 2024;128:1-9.
  • 16. Yan J, Yang S, Han L, Ba X, Shen P, Lin W, et al. Dyslipidemia in rheumatoid arthritis: the possible mechanisms. Front Immunol. 2023;14:1254753.
  • 17. Daïen CI, Duny Y, Kohler C, Goeb V, Daurès JP. Effect of TNF inhibitors on lipid profile in rheumatoid arthritis: a systematic review with meta-analysis. Ann Rheum Dis. 2012;71(6):862-8.
  • 18. Hammam N, Abdel-Wahab N, Gheita TA. Atherogenic index of plasma in women with rheumatoid arthritis and systemic lupus erythematosus: a 10-year potential predictor of cardiovascular disease. Curr Rheumatol Rev. 2021;17(1):122-30.
  • 19. Gonzalez-Gonzalez V, García-García C, Benavides-Haro DE. Association of plasma atherogenic index with subclinical atherosclerosis in rheumatoid arthritis. Ann Rheum Dis. 2024;83(Suppl 1):6593.
  • 20. Lim WS, Sinha A, Toh SA. The effects of anti-TNF-α biologics on insulin resistance in rheumatoid arthritis: a systematic review and meta-analysis. Diabetes Metab Syndr. 2024;18(5):103029.
  • 21. Burska AN, Sakthiswary R, Sattar N. Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis and ankylosing spondylitis: a systematic review and meta-analysis. PLoS One. 2015;10(6):e0128889.

Romatoid Artritte DMARD ve Anti-TNF Tedavilerinin İnflamatuvar Belirteçler, Lipid Profili ve İnsülin Direnci Üzerine Etkileri: Kontrollü Bir Çalışma

Year 2026, Volume: 16 Issue: 1, 32 - 36, 31.01.2026
https://doi.org/10.16899/jcm.1808008

Abstract

Amaç
Bu çalışmanın amacı, romatoid artrit (RA) hastalarında hastalık modifiye edici antirromatizmal ilaçlar (DMARD’lar) ile anti-tümör nekroz faktör (anti-TNF) tedavisinin inflamatuvar belirteçler, lipid profili ve insülin direnci üzerindeki etkilerini karşılaştırmak ve biyolojik tedavilerin olası kardiyovasküler etkilerini değerlendirmektir.
Gereç ve Yöntem
Bu tek merkezli, prospektif çalışmaya Mayıs 2012 ile Mayıs 2013 tarihleri arasında toplam 122 katılımcı dahil edilmiştir: DMARD tedavisi alan 35 RA hastası, anti-TNF ajanları ile tedavi edilen 31 RA hastası ve 56 sağlıklı kontrol. İnflamatuvar belirteçler [eritrosit sedimantasyon hızı (ESR), C-reaktif protein (CRP), romatoid faktör (RF)], lipid profili [toplam kolesterol, trigliserit, yüksek yoğunluklu lipoprotein (HDL), plazmanın aterojenik indeksi (AIP)] ve glisemik parametreler [açlık glukozu, insülin, insülin direncinin homeostaz modeli değerlendirmesi (HOMA-IR)] incelenmiştir.
Bulgular
ESR ve CRP düzeyleri, kontrol grubuna kıyasla RA gruplarında anlamlı derecede yüksek bulunmuştur (p<0.001) ve CRP düzeyi anti-TNF grubunda DMARD grubuna göre daha yüksek saptanmıştır. RF pozitifliği RA hastalarında belirgin şekilde artmıştır (p<0.001). Lipid profili veya AIP açısından gruplar arasında anlamlı bir fark bulunmamıştır (p>0.05). İnsülin ve açlık glukoz düzeyleri benzer iken, HOMA-IR kontrol grubunda daha yüksek ve RA gruplarında marjinal olarak daha düşük bulunmuştur (p=0.049).
Sonuç
RA hastalarında inflamasyon belirgin şekilde artmışken, lipid profili ve AIP tedavi grupları arasında farklılık göstermemiştir. İnflamasyonun baskılanması, insülin direncinde kısmi bir iyileşme ile ilişkilendirilmiştir. RA’daki kardiyometabolik risk değerlendirmesi yapılırken yalnızca klasik lipid parametreleri değil, inflamasyon ve insülin direnci gibi çok faktörlü belirleyiciler de dikkate alınmalıdır.

Ethical Statement

Çalışma, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi Klinik Araştırmalar Etik Kurulu’nun izniyle gerçekleştirilmiştir (Onay No: 2012/8).

References

  • 1. Firestein GS, Kelley WN. Kelley and Firestein's Textbook of Rheumatology. 11th ed. Philadelphia: Elsevier; 2021.
  • 2. Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360-72.
  • 3. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130-6.
  • 4. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328-37.
  • 5. Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003;62(8):722-7.
  • 6. Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59(12):1690-7.
  • 7. Myasoedova E, Crowson CS, Kremers HM, Roger VL, Fitz-Gibbon PL, Therneau TM, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70(3):482-7.
  • 8. Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum. 2018;48(1):22-7.
  • 9. Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-99.
  • 10. European Alliance of Associations for Rheumatology (EULAR). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2022;81(6):787-99.
  • 11. Peters MJL, Symmons DPM, McCarey D, Dijkmans BAC, Nicola P, Kvien TK, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2019;79(6):768-76.
  • 12. Macáková K, Zavada J, Jebavý L, Šenolt L. Metabolic effects of anti-TNF-α treatment in rheumatoid arthritis. Diseases. 2023;11(4):164.
  • 13. Van den Oever IAM, Raterman HG, Nurmohamed MT, Simsek S. The effect of anti-TNF treatment on body composition and insulin resistance in rheumatoid arthritis patients. Rheumatol Ther. 2021;7(1):201-11.
  • 14. Ceccarelli F, Massafra U, Perricone C, Idolazzi L, Giacomelli R, Tirri R, et al. Anti-TNF treatment response in rheumatoid arthritis patients with moderate disease activity: a prospective observational multicentre study (MODERATE). Clin Exp Rheumatol. 2017;35(1):24-32.
  • 15. Drosos AA, Venetsanopoulou AA, Pelechas E, Voulgari PV. Exploring cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Eur J Intern Med. 2024;128:1-9.
  • 16. Yan J, Yang S, Han L, Ba X, Shen P, Lin W, et al. Dyslipidemia in rheumatoid arthritis: the possible mechanisms. Front Immunol. 2023;14:1254753.
  • 17. Daïen CI, Duny Y, Kohler C, Goeb V, Daurès JP. Effect of TNF inhibitors on lipid profile in rheumatoid arthritis: a systematic review with meta-analysis. Ann Rheum Dis. 2012;71(6):862-8.
  • 18. Hammam N, Abdel-Wahab N, Gheita TA. Atherogenic index of plasma in women with rheumatoid arthritis and systemic lupus erythematosus: a 10-year potential predictor of cardiovascular disease. Curr Rheumatol Rev. 2021;17(1):122-30.
  • 19. Gonzalez-Gonzalez V, García-García C, Benavides-Haro DE. Association of plasma atherogenic index with subclinical atherosclerosis in rheumatoid arthritis. Ann Rheum Dis. 2024;83(Suppl 1):6593.
  • 20. Lim WS, Sinha A, Toh SA. The effects of anti-TNF-α biologics on insulin resistance in rheumatoid arthritis: a systematic review and meta-analysis. Diabetes Metab Syndr. 2024;18(5):103029.
  • 21. Burska AN, Sakthiswary R, Sattar N. Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis and ankylosing spondylitis: a systematic review and meta-analysis. PLoS One. 2015;10(6):e0128889.
There are 21 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases, Rheumatology and Arthritis
Journal Section Research Article
Authors

Hatice Selcen Toprak 0000-0002-6504-3875

Refik Demirtunç 0000-0003-0056-5645

Submission Date October 21, 2025
Acceptance Date December 22, 2025
Publication Date January 31, 2026
Published in Issue Year 2026 Volume: 16 Issue: 1

Cite

AMA Toprak HS, Demirtunç R. Effects of DMARD and Anti-TNF Therapies on Inflammatory Markers, Lipid Profile, and Insulin Resistance in Rheumatoid Arthritis: A Controlled Study. J Contemp Med. January 2026;16(1):32-36. doi:10.16899/jcm.1808008