Romatoid artrit hastalığında ilaç uyumu, tedaviye devam etme ve tedavinin kesilmesi: tek merkezli gerçek dünya çalışması

Abstract

Amaçlar: Romatoid artrit (RA) tedavisi, hastalık modifiye edici antiromatizmal ilaçların (DMARD) düzenli kullanımına bağlıdır, ancak gerçek hayatta tedaviye uyum ve devamlılık optimum düzeyde değildir. Tedaviye uyumsuzluk hastalık kontrolünü zorlaştırırken, uzun süreli tedavi enfeksiyon riskini artırabilir. Türk RA hastalarında bu konudaki veriler sınırlıdır. Yöntem: Bu retrospektif çalışmada, 2010 ACR/EULAR RA kriterlerini karşılayan ve Hacettepe Üniversitesi'nde en az 6 ay takip edilen 107 yetişkin hasta analiz edildi. Reçete edilen DMARD dozunun ≥%80'ini almak olarak tanımlanan uyum, hasta bildirimi ve dosya incelemesi yoluyla değerlendirildi. Tedaviye devam etme, tedaviyi bırakma nedenleri ve klinik sonuçlar belgelendi. Hastalık aktivitesi DAS28-CRP ile ölçüldü. Çok değişkenli lojistik regresyon, uyumsuzluk, tedaviyi bırakma ve enfeksiyon öngörücülerini belirledi. Bulgular: Genel olarak, %28,0'ı düzensiz ilaç kullanımı bildirirken, %42,1'i en az bir csDMARD'ı bırakmıştı. Yaygın uyumsuzluk nedenleri arasında takipsizlik (%31,8) ve yan etki endişeleri (%27,3) bulunmakta idi. Uyumsuzluk nedenlerinin bağımsız değişkenleri arasında uzun takip süresi (OR 1,040, %95 GA 1,005-1,076), sık doktora başvurma VAS'ı (OR 1,035, %95 GA 1,006-1,065) ve hidroksiklorokin kullanımı (OR 4,733, %95 GA 1,450-15,543) yer almakta idi. Tedaviye uyumsuzluk, en az bir csDMARD'ın kesilmesi ile güçlü ilişkili (OR 9,22, %95 CI 2,12-39,87) iken daha düşük BMI ile arasında sınırda bir ilişki saptandı (OR 0,87, %95 CI 0,76-1,00). Tedavi uyumu, ilginç şekilde yüksek enfeksiyon riskiyle ilişkilendirildi (OR 4,163, %95 CI 1,030-16,833). Sülfasalazin en yüksek kesilme oranına (%80,0) sahipti ve en kısa ortanca tedavi tutma süresini (9,5 ay) gösterdi. Tartışma: RA'da tedaviye uyumsuzluk sık görülür ve csDMARD tedavisinin kesilmesiyle yakından ilişkilidir; bu da davranışsal ve algısal engellerin ele alınması gerektiğini vurgulamaktadır. Uyum ve enfeksiyonlar arasındaki ilişki, uzun süreli bağışıklık baskılanması olan hastalarda dikkatli izlemenin önemini vurgulamaktadır. Sülfasalazinin bu durumda uzun süreli tedavi için daha az uygun olabileceğini düşündürmektedir.

Keywords

• Romatoid artrit
• İlaç uyumu
• DMARD kalıcılığı
• Tedavinin kesilmesi

Medication adherence, treatment persistence, and discontinuation in rheumatoid arthritis: a single-center real-world study

Abstract

Aims: Rheumatoid arthritis (RA) management depends on sustained use of disease-modifying antirheumatic drugs (DMARDs), yet adherence and persistence remain suboptimal in real life. Non-adherence may undermine disease control, while long-term therapy can increase infection risk. Data on these parameters in Turkish RA patients are scarce. Methods: In this retrospective study, 107 adults fulfilling 2010 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) RA criteria and followed ≥6 months at Hacettepe University were analyzed. Adherence, defined as intake of ≥80% prescribed DMARDs doses, was assessed via patient self-report and chart review. Persistence, discontinuation reasons, and clinical outcomes were documented. Disease activity was measured with disease activity score in 28 joints with C-reactive protein (DAS28-CRP). Multivariate logistic regression identified predictors of non-adherence, discontinuation, and infection. Results: Overall, 28.0% reported irregular medication use, and 42.1% discontinued at least one conventional synthetic DMARDs (csDMARDs). Common non-adherence reasons were lack of routine (31.8%) and adverse effect concerns (27.3%). Independent predictors of non-adherence included longer follow-up (OR 1.040, 95% CI 1.005–1.076), higher baseline physician Visual Analog Scale (VAS) (OR 1.035, 95% CI 1.006–1.065), and hydroxychloroquine use (OR 4.733, 95% CI 1.450–15.543). Non adherence strongly predicted the discontinuation of at least one csDMARD (OR 9.22, 95% CI 2.12–39.87), while lower body-mass index (BMI) showed a borderline association with treatment discontinuation (OR 0.87, 95% CI 0.76–1.00). Adherence was paradoxically associated with higher infection risk (OR 4.163, 95% CI 1.030–16.833). Sulfasalazine showed the highest discontinuation rate (80.0%) and shortest median retention (9.5 months). Conclusion: Non-adherence is frequent and closely linked to csDMARD discontinuation in RA, underscoring the need to address behavioral and perceptual barriers. The association between adherence and infections highlights the importance of vigilant monitoring in patients with prolonged immunosuppression. Drug-specific patterns suggest sulfasalazine may be less suitable for long-term therapy in this setting.

Keywords

• Rheumatoid arthritis
• medication adherence
• DMARD persistence
• treatment discontinuation

References

1. Brown P, Pratt AG, Hyrich KL. Therapeutic advances in rheumatoid arthritis. BMJ. 2024;384:e070856. doi:10.1136/bmj-2022-070856
2. Smolen JS, Aletaha D. The assessment of disease activity in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28(3 Suppl 59):S18-S27.
3. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44-48. doi:10.1002/art.1780380107
4. Murage M, Tongbram V, Feldman S, et al. Medication adherence and persistence in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis: a systematic literature review. Patient Prefer Adherence. 2018;12:1483-1503. doi:10.2147/PPA.S167508
5. Pope JE, Rampakakis E, Movahedi M, et al. Treatment patterns in rheumatoid arthritis after discontinuation of methotrexate: data from the Ontario Best Practices Research Initiative (OBRI). Clin Exp Rheumatol. 2018;36(2):215-222.
6. Cruz BH, Garnica IU, Parera RS, et al. Disease-modifying antirheumatic drug prescription patterns in adult rheumatoid arthritis patients in routine clinical practice in Spain. Eur J Rheumatol. 2020;7(4):149-157. doi:10.5152/eurjrheum.2020.19053
7. Yang Z, Alveyn E, Russell M, et al. Association of patient- and hospital-level predictors with patterns of initial treatment in patients with rheumatoid arthritis: findings from a national cohort study. Rheumatology. 2025;64(6):3379-3387. doi:10.1093/rheumatology/keae717
8. Dore RK, Antonova J, Huan H, Gorritz M, Genovese MC. Short duration of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) before and after becoming a csDMARD inadequate responder in rheumatoid arthritis patients. Ann Rheum Dis. 2019;78:700. doi:10.1136/annrheumdis-2019-eular.1848

9. 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
10. Balsa A, García De Yébenes MJ, et al. Multilevel factors predict medication adherence in rheumatoid arthritis: a 6-month cohort study. Ann Rheum Dis. 2022;81(3):327-334. doi:10.1136/annrheumdis-2021-221163
11. Li L, Cui Y, Yin R, et al. Medication adherence has an impact on disease activity in rheumatoid arthritis: a systematic review and meta-analysis. Patient Prefer Adherence. 2017;11:1343-1356. doi:10.2147/PPA.S140457
12. Nakagawa S, Nakaishi M, Hashimoto M, et al. Effect of medication adherence on disease activity among Japanese patients with rheumatoid arthritis. PLoS One. 2018;13(11):e0206943. doi:10.1371/journal.pone. 0206943
13. Pasma A, Van’T Spijker A, Hazes JMW, Busschbach JJV, Luime JJ. Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: a systematic review. Semin Arthritis Rheum. 2013;43(1):18-28. doi:10.1016/j.semarthrit.2012.12.001
14. Van Den Bemt BJF, Van Den Hoogen FHJ, Benraad B, Hekster YA, Van Riel PLCM, Van Lankveld W. Adherence rates and associations with nonadherence in patients with rheumatoid arthritis using disease modifying antirheumatic drugs. J Rheumatol. 2009;36(10):2164-2170. doi:10.3899/jrheum.081204
15. Gu Z, Xia Y, Yin R, et al. Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis. Patient Prefer Adherence. 2016;10:735-742. doi:10.2147/PPA.S98034
16. Grijalva CG, Chung CP, Arbogast PG, Stein CM, Mitchel EF, Griffin MR. Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007;45(10 Supl 2):S66-S76. doi:10.1097/MLR.0b013e 318041384c
17. Caporali R, Caprioli M, Bobbio-Pallavicini F, Montecucco C. DMARDS and infections in rheumatoid arthritis. Autoimmun Rev. 2008;8(2):139-143. doi:10.1016/j.autrev.2008.05.001
18. Dey M, Zhao SS, Moots RJ, Bergstra SA, Landewe RB, Goodson NJ. The association between increased body mass index and response to conventional synthetic disease-modifying anti-rheumatic drug treatment in rheumatoid arthritis: results from the METEOR database. Rheumatology. 2022;61(2):713-722. doi:10.1093/rheumatology/keab389
19. McCulley CB, Barton JL, Cannon GW, et al. Body mass index and persistence of conventional DMARDs and TNF inhibitors in rheumatoid arthritis. Clin Exp Rheumatol. 2019;37(3):422-428.
20. Kerschbaumer A, Sepriano A, Bergstra SA, et al. Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2023;82(1):95-106. doi:10.1136/ard-2022-223365
21. Schett G, Emery P, Tanaka Y, et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016;75(8):1428-1437. doi:10.1136/annrheumdis-2016-209201
22. Bettembourg-Brault I, Gossec L, Pham T, Gottenberg JE, Damiano J, Dougados M. Leflunomide in rheumatoid arthritis in daily practice: treatment discontinuation rates in comparison with other DMARDs. Clin Exp Rheumatol. 2006;24(2):168-171.