Risk of Serious Infections in Patients with Rheumatoid Arthritis Receiving Biological and Targeted Synthetic DMARDs: A Single-Center, Retrospective Cohort Study

Öz

Objective: To evaluate the effect of biological (bDMARD) and targeted synthetic (tsDMARD) disease-modifying antirheumatic drugs on the risk of serious infections (SI) and to identify associated risk factors in patients with rheumatoid arthritis (RA). Materials and Methods: This retrospective cohort study included RA patients followed at a single tertiary care center between August 2018 and August 2024. Patients meeting the ACR/EULAR 2010 criteria were divided into three groups: those receiving b/tsDMARDs (n=199), those receiving only conventional synthetic DMARDs (csDMARDs) (n=50), and healthy controls (n=50). SI was defined as infections requiring hospitalization. Demographic, clinical, and treatment data were collected from electronic medical records. Multiple logistic regression analysis was used to analyze risk factors. ROC curve analysis was performed to evaluate the effect of treatment duration. Statistical analyses were performed using SPSS version 27 (IBM). Results: SI occurred in 15.8% (n=31) of patients in the b/tsDMARD group, compared to 14% (n=7) in the csDMARD group and 4% (n=2) in the control group. b/tsDMARD use significantly increased the risk of SI compared to healthy controls (OR: 3.66; 95% CI: 1.09-12.28; p=0.035), but no significant difference was found compared to the csDMARD group (p=0.781). In multiple regression analysis, advanced age (p=0.005) and prolonged b/tsDMARD use (p=0.014) were identified as independent risk factors for SI. ROC analysis identified 57.5 months of treatment duration as a threshold value for SI risk (Area Under the Curve: 0.624; p=0.023). Treatment duration exceeding this threshold increased the risk by 1.175-fold (p=0.009). Among drugs, rituximab use was associated with a higher risk of SI compared to other agents (OR: 1.72; p=0.005). Pneumonia was the most common site of SI. Conclusion: b/tsDMARD therapy increases the risk of SI in RA patients, particularly with prolonged use and in advanced age. The risk may vary among different biological agents; in our study, rituximab was associated with a higher risk. These findings emphasize the importance of personalized risk-benefit assessment and close monitoring for infections in RA management.

Anahtar Kelimeler

• Rheumatoid Arthritis
• Biological DMARD
• Infection

Destekleyen Kurum

none

Etik Beyan

Hatay Mustafa Kemal University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Date: 03.09.2024, Number: 05)

Teşekkür

none

Biyolojik ve Hedefe Yönelik Sentetik DMARD Kullanan Romatoid Artrit Hastalarında Ciddi Enfeksiyon Riski: Tek Merkezli, Retrospektif Bir Kohort Çalışması

Öz

Amaç: Biyolojik (bDMARD) ve hedefe yönelik sentetik (tsDMARD) hastalığı modifiye edici antiromatizmal ilaçların ciddi enfeksiyon (SI) riski üzerindeki etkisini değerlendirmek ve romatoid artrit (RA) hastalarında ilişkili risk faktörlerini belirlemek. Gereç ve Yöntemler: Bu retrospektif kohort çalışmasına, Ağustos 2018 ile Ağustos 2024 tarihleri ​​arasında tek bir üçüncü basamak sağlık merkezinde takip edilen RA hastaları dahil edildi. ACR/EULAR 2010 kriterlerini karşılayan hastalar üç gruba ayrıldı: b/tsDMARD alanlar (n=199), yalnızca konvansiyonel sentetik DMARD (csDMARD) alanlar (n=50) ve sağlıklı kontroller (n=50). SI, hastaneye yatış gerektiren enfeksiyonlar olarak tanımlandı. Demografik, klinik ve tedavi verileri elektronik tıbbi kayıtlardan toplandı. Risk faktörlerini analiz etmek için çoklu lojistik regresyon analizi kullanıldı. Tedavi süresinin etkisini değerlendirmek için ROC eğrisi analizi yapıldı. İstatistiksel analizler SPSS sürüm 27 (IBM) kullanılarak yapıldı. Bulgular: b/tsDMARD grubundaki hastaların %15,8'inde (n=31) SI meydana gelirken, csDMARD grubunda bu oran %14 (n=7) ve kontrol grubunda %4 (n=2) idi. b/tsDMARD kullanımı, sağlıklı kontrollerle karşılaştırıldığında SI riskini önemli ölçüde artırdı (OR: 3,66; %95 CI: 1,09-12,28; p=0,035), ancak csDMARD grubuyla karşılaştırıldığında önemli bir fark bulunamadı (p=0,781). Çoklu regresyon analizinde, ileri yaş (p=0,005) ve uzun süreli b/tsDMARD kullanımı (p=0,014) SI için bağımsız risk faktörleri olarak belirlendi. ROC analizi, 57,5 ​​aylık tedavi süresini SI riski için bir eşik değer olarak belirledi (Eğri Altındaki Alan: 0,624; p=0,023). Bu eşiği aşan tedavi süresi, riski 1,175 kat artırmıştır (p=0,009). İlaçlar arasında, rituksimab kullanımı diğer ajanlara kıyasla daha yüksek SI riski ile ilişkilendirilmiştir (OR: 1,72; p=0,005). En sık görülen SI bölgesi pnömonidir. Sonuç: b/tsDMARD tedavisi, özellikle uzun süreli kullanımda ve ileri yaşta RA hastalarında SI riskini artırmaktadır. Risk, farklı biyolojik ajanlar arasında değişiklik gösterebilir; çalışmamızda rituksimab daha yüksek bir risk ile ilişkilendirilmiştir. Bu bulgular, RA yönetiminde kişiselleştirilmiş risk-fayda değerlendirmesinin ve enfeksiyonlar açısından yakın takibin önemini vurgulamaktadır.

Anahtar Kelimeler

• Romatoid Artrit
• Biyolojik DMARD
• Enfeksiyon

Destekleyen Kurum

yok

Etik Beyan

Hatay Mustafa Kemal Üniversitesi Tıp Fakültesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu (Tarih: 03.09.2024, Sayı: 05)

Teşekkür

yok

Kaynakça

1. Cross M, Smith E, Hoy D, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014; 73:1316-1322.
2. Almutairi KB, Nossent JC, Preen DB, et al. The Prevalence of Rheumatoid Arthritis: A Systematic Review of Population-based Studies. J Rheumatol. 2021; 48(5):669-676.
3. Chauhan K, Jandu JS, Brent LH, et al. Rheumatoid Arthritis. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2024.
4. Au K, Reed G, Curtis JR, et al. High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis. Ann Rheum Dis. 2011; 70:785-791.
5. Smolen JS, Landewé RBM, Bijlsma JWJ, 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):685-699.
6. Singh JA, Cameron C, Noorbaloochi S, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet. 2015; 386:258-265.
7. Quartuccio L, Zabotti A, Del Zotto S, et al. Risk of serious infection among patients receiving biologics for chronic inflammatory arthritis: a real-life study. Clin Exp Rheumatol. 2018; 36:1011-1018.
8. Johnston SS, Turpcu A, Shi N, Fowler R, Chu BC, Alexander K. Risk of infections in rheumatoid arthritis patients switching from anti-TNF agents to rituximab, abatacept, or another anti-TNF agent, a retrospective administrative claims analysis. Semin Arthritis Rheum. 2013;43(1):39-47.

9. Kelesidis T, Daikos G, Boumpas D, et al. Does rituximab increase the incidence of infectious complications? A narrative review. Int J Infect Dis. 2011;15: e2-16.
10. Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology. 2013; 52(1):53-61.
11. Ikari Y, Yajima N, Miwa Y. The association between age and adverse events due to biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A retrospective cohort study. Medicine (Baltimore). 2020;99(52): e23861
12. Ozen G, Pedro S, Wolfe F, et al. Medications associated with fracture risk in patients with rheumatoid arthritis. Ann Rheum Dis. 2019; 78:1041-1047.
13. 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; 73:62-68.
14. Taylor PC, Atzeni F, Balsa A, et al. The key comorbidities in patients with rheumatoid arthritis: A narrative review. J Clin Med. 2021; 10(3):509.
15. van Vollenhoven RF, Emery P, Bingham CO, et al. Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA. Ann Rheum Dis. 2013; 72(9):1496-1502.
16. Tallantyre EC, Whittam DH, Jolles S, et al. Secondary antibody deficiency: a complication of anti-CD20 therapy for neuroinflammation. J Neurol. 2018; 265(5):1115-1122.
17. Salliot C, Dougados M, Gossec L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2009; 68:25-32.
18. Moon SM, Han K, Jung J-H, et al. Risk of pneumonia in individuals with rheumatoid arthritis. BMJ Open Respir Res. 2025;12: e002664.
19. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum. 2006; 54(2):628-634.