JHSM

Journal of Health Sciences and Medicine (JHSM) is an unbiased, peer-reviewed, and open access international medical journal. The Journal publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports, and clinical images, invited reviews, editorials, letters, comments, and related knowledge.

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Original Article
Does the presence of comorbidities in rheumatoid arthritis patients impact initial tumor necrosis factor inhibitor treatment response and retention rates?
Aims: We aimed to evaluate the effect of comorbidities on the first tumor necrosis factor inhibitor (TNFi) treatment response and retention in patients with rheumatoid arthritis (RA).
Methods: The study included adult RA patients (with M05 and M06 ICD codes) registered in the TURKBIO database and receiving their first TNFi treatment. Data on demographic, clinical, and laboratory features, disease activity scores, and other follow-up parameters (at the beginning and months 6 and 12) were collected. The Log-Rank test and Kaplan-Meier curve were used to determine the TNFi retention rates.
Results: There were 1172 bio-naive RA patients who initiated their first TNFi treatments. The median age (IQR) of the patients was 53 (51-61), and 79.8% (n=935) were women. The most commonly used TNFi was etanercept (38.9%), followed by adalimumab (27.9%), certolizumab (13.8%), golimumab (10.8%), and infliximab (8.7%). The most prevalent comorbidities in patients were hypertension (32.6%), obesity (32.6%), osteoporosis (22.3%), asthma/COPD (17.9%), and diabetes mellitus (15.7%). The presence of comorbidities at the beginning of TNFi treatment did not affect DAS28 CRP responses at months 6 and 12 (p=0.18 and p=0.83, respectively) and the continuation rates of the first TNFi drug. After conducting a thorough analysis that factored in variables including gender, age over 60 years, smoking, serologic status, presence of erosion, and basal disease activity scores, it was determined that there were no statistically significant hazard ratios (HR) for the first TNFi persistence. However, there was a 5% decrease in adherence to the first TNFi drug with an increase in median disease duration (HR 0.95, 95% CI=0.90-1.00, p=0.048).
Conclusion: It has been observed that the presence of comorbidities in patients with RA does not significantly affect the TNFi treatment response and retention rate. However, evidence suggests that as the duration of the disease increases, the continuation of the first TNFi drug may decrease.


1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016; 388(10055):2023-2038. doi:10.1016/S0140-6736(16)30173-8
2. Stouten V, Westhovens R, De Cock D, et al. Having a co-morbidity predicts worse outcome in early rheumatoid arthritis despite intensive treatment: a post hoc evaluation of the pragmatic randomized controlled CareRA trial. Rheumatology. 2021;60(8):3699-3708. doi:10.1093/rheumatology/ keaa841
3. Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2014; 73(1):62-68. doi:10.1136/annrheumdis-2013-204223
4. Nakajima A, Inoue E, Shimizu Y, et al. The presence of comorbidity affects both treatment strategies and outcomes in disease activity, physical function, and quality of life in patients with rheumatoid arthritis. Clin Rheumatol. 2015;34:441-449. doi:10.1007/s10067-014-2750-8
5. England BR, Roul P, Yang Y, et al. Burden and trajectory of multimorbidity in rheumatoid arthritis: a matched cohort study from 2006 to 2015. Ann Rheum Dis. 2021;80(3):286-292. doi:10.1136/annrheumdis-2020-218282
6. Roodenrijs NM, van der Goes MC, Welsing PM, et al. Non-adherence in difficult-to-treat rheumatoid arthritis from the perspectives of patients and rheumatologists: a concept mapping study. Rheumatology. 2021; 60(11):5105-5116. doi:10.1093/rheumatology/keab130
7. Dey M, Nagy G, Nikiphorou E. Comorbidities and extra-articular manifestations in difficult-to-treat rheumatoid arthritis: different sides of the same coin? Rheumatology. 2023;62(5):1773-1779. doi:10.1093/rheumatology/keac584
8. Marchesoni A, Zaccara E, Gorla R, et al. TNFα antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann New York Acad Sci. 2009;1173(1):837-846. doi:10.1111/j.1749-6632.2009.04621.x
9. Hetland ML, Christensen IJ, Tarp U, et al. Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum. 2010;62(1): 22-32. doi:10.1002/art.27227
10. Favalli EG, Pregnolato F, Biggioggero M, et al. Twelve-year retention rate of first-line tumor necrosis factor inhibitors in rheumatoid arthritis: real-life data from a local registry. Arthritis Care Res (Hoboken). 2016; 68(4):432-439. doi:10.1002/acr.22788
11. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. doi:10.1002/art.27584
12. Favalli EG, Raimondo MG, Becciolini A, Crotti C, Biggioggero M, Caporali R. The management of first-line biologic therapy failures in rheumatoid arthritis: current practice and future perspectives. Autoimmun Rev. 2017;16(12):1185-1195. doi:10.1016/j.autrev.2017.10.002
13. Radner H, Smolen JS, Aletaha D. Comorbidity affects all domains of physical function and quality of life in patients with rheumatoid arthritis. Rheumatology. 2011;50(2):381-388. doi:10.1093/rheumatology/keq334
14. Radner H, Yoshida K, Hmamouchi I, Dougados M, Smolen JS, Solomon DH. Treatment patterns of multimorbid patients with rheumatoid arthritis: results from an international cross-sectional study. J Rheumatol. 2015;42(7):1099-1104. doi:10.3899/jrheum.141534
15. Armagan B, Sari A, Erden A, et al. Starting of biological disease modifying antirheumatic drugs may be postponed in rheumatoid arthritis patients with multimorbidity: single center real life results. Medicine. 2018;97(13):e9930. doi:10.1097/MD.0000000000009930
16. Nikiphorou E, De Lusignan S, Mallen C, et al. Prognostic value of comorbidity indices and lung diseases in early rheumatoid arthritis: a UK population-based study. Rheumatology. 2020;59(6):1296-1305. doi: 10.1093/rheumatology/kez409
17. Stouten V, Pazmino S, Verschueren P, et al. Comorbidity burden in the first three years after diagnosis in patients with rheumatoid arthritis, psoriatic arthritis or spondyloarthritis: a general practice registry-based study. RMD Open. 2021;7(2):e001671. doi:10.1136/rmdopen-2021-001671
18. Baillet A, Gossec L, Carmona L, et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheumat Dis. 2016;75(6):965-973. doi:10.1136/annrheumdis-2016-209233
19. Nagy G, Roodenrijs NM, Welsing PM, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. Ann Rheumat Dis. 2022;81(1):20-33. doi:10.1136/annrheumdis-2021-220973
20. Roodenrijs NM, Kedves M, Hamar A, et al. Diagnostic issues in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis. RMD Open. 2021;7(1):e001511. doi:10.1136/rmdopen-2020-001511
21. Ranganath VK, Maranian P, Elashoff DA, et al. Comorbidities are associated with poorer outcomes in community patients with rheumatoid arthritis. Rheumatology. 2013;52(10):1809-1817. doi:10.1093/rheumatology/ket224
22. Busby AD, Wason J, Pratt AG, Young A, Isaacs JD, Nikiphorou E. The role of comorbidities alongside patient and disease characteristics in long-term disease activity in RA using UK inception cohort data. Rheumatology. 2022;61(11):4297-4304. doi:10.1093/rheumatology/keac139
23. Calvo-Gutiérrez J, López-Medina C, Otero-Varela L, et al. Impact of multimorbidity on the first ts/bDMARD effectiveness and retention rate after two years of follow-up in patients with rheumatoid arthritis from the BIOBADASER registry. Arthritis Res Therapy. 2024;26(1):57. doi:10.1186/s13075-024-03287-9
24. Favalli EG, Pontikaki I, Becciolini A, et al. Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult-and juvenile-onset populations: similarities and differences. Clin Rheumatol. 2017;36:1747-1755. doi:10.1007/s10067-017-3712-8
25. Soliman MM, Ashcroft DM, Watson KD, Lunt M, Symmons DP, Hyrich KL. Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Ann Rheumat Dis. 2011;70(4):583-589. doi:10.1136/ard.2010.139774
26. Iannone F, Gremese E, Atzeni F, et al. Longterm retention of tumor necrosis factor-α inhibitor therapy in a large Italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors. J Rheumatol. 2012;39(6):1179-1184. doi:10.3899/jrheum. 111125
27. van Mulligen E, Ahmed S, Weel AE, Hazes JM, van der Helm-van Mil AH, de Jong PH. Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands. Clin Rheumatol. 2021;40:2177-2183. doi:10.1007/s10067-020-05567-6
28. Heiberg MS, Koldingsnes W, Mikkelsen K, et al. The comparative one-year performance of anti-tumor necrosis factor α drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Care Res. 2008;59(2):234-240. doi:10.1002/art.23333
29. Naffaa ME, Hassan F, Golan-Cohen A, et al. Factors associated with drug survival on first biologic therapy in patients with rheumatoid arthritis: a population-based cohort study. Rheumatol Int. 2021;41(11):1905-1913. doi:10.1007/s00296-021-04989-y
30. Ebina K, Etani Y, Maeda Y, et al. Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. RMD Open. 2023;9(3):e003160. doi:10.1136/rmdopen-2023- 003160
Volume 8, Issue 2, 2025
Page : 292-297
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