Romatoid Artrit Tanılı Hastalarda Biyolojik İlaç Sağkalımını Etkileyen Faktörler: Türkiye’den Tek Merkezli Bir Çalışma

Yıl 2023, Cilt: 18 Sayı: 1, 73 - 84, 16.03.2023

Beliz Karataş , Barış Yılmazer

https://doi.org/10.17517/ksutfd.1068756

Öz

Amaç: Çalışmanın amacı; erişkin romatoid artrit (RA) hastalarında biyolojik ajan tedavilerinde ilaçta sağkalımı etkileyen faktörleri belirlemektir.
Gereç ve Yöntemler: Çalışmamızda 2013-2016 yılları arasında Trakya Üniversitesi Tıp Fakültesi Hastanesi Romatoloji kliniğinde RA tanısı ile ayaktan ya
da yatırılarak takip edilmiş 245 hastanın verileri retrospektif olarak incelendi. Otuz yedi hastanın verileri eksik olduğundan çalışmadan dışlandı. Kalan 208
hastanın verileri değerlendirildi.
Bulgular: Çalışmamızda ilerleyen yaşın ilaç sağkalım süresini 0.48 kat ( %95 güven aralığı 0.23-0.97), kadın cinsiyetin 3 kat (%95 güven aralığı 1.09-10.3),
hiperlipidemi varlığının 8 kat (%95 güven aralığı 2.12-32.5), tedavi öncesi eritrosit sedimantasyon hızı (ESH) yüksekliğinin 1.03 kat (%95 güven aralığı
1.01-1.04), Hepatit B yüzey antijen pozitifliğinin (HBsAg) 9.2 kat (%95 güven aralığı 2.4-35.3), sitrulinlenmiş proteine karşı oluşan antikor (Anti-CCP)
pozitifliğinin 2.9 kat (%95 güven aralığı 1.3-6.4), glukokortikoid kullanımının 0.36 kat (%95 güven aralığı 0.17-0.76) kısalttığını gösterdik. Buna karşın;
kronik böbrek hasarı olan hastalarda ilaçta kalma süresinin 0.18 kat (%95 güven aralığı 0.06-0.57) uzadığı gözlemlenmiştir.
Sonuç: RA hastalarına biyolojik ilaç başlarken bazı parametreler ilaçta sağ kalımı ön görmede yardımcı olabilir. Etki sırasına gore; HBsAg pozitifliği, hi-
perlipidemi varlığı, kadın cinsiyet, anti-CCP pozitifliği, ESH yüksekliği, ileri yaş ve glukokortikoid kullanımı ilaçta kalma süresi için negatif marker iken;
kronik böbrek hasarı ise pozitif marker olabilir.

Anahtar Kelimeler

Biyolojik ajanlar, Romatoid artrit, Tümör nekroz faktör

Factors Affecting Survival on Biologic Treatments in Patients with Rheumatoid Arthritis: A Single-Center Study From Turkey

Öz

Objective: In our study, we aimed to determine the factors affecting survival on biologic treatment in adult rheumatoid arthritis (RA) patients using biolog-
ical drugs.
Materials and Methods: In our study, the data of 245 patients who were followed up with the diagnosis of RA in the Rheumatology Clinic of Trakya
University Medical Faculty Hospital between 2013 and 2016 were analyzed retrospectively. 37 patients were excluded due to missing data. The data of the
remaining 208 patients were evaluated.
Results: In our study, we found that drug survival was reduced by 0.48 times (95% CI 0.23-0.97) in elderly patients and 3 times (95% CI 1.09-10.3) in
females. According to the results of our study, drug survival is shortened 8 times (95% CI 2.12-32.5) in patients with hyperlipidemia and 1.03 times (95%
CI 1.01-1.04) in patients with high pretreatment erythrocyte sedimentation rate (ESR). In addition, we found that shorter drug survival 9.2 times (95% CI
2.4-35.3) in patients with Hepatitis B surface antigen (HBsAg) positivity, 2.9 times (95% CI 1.3-6.4) in patients with antibody positivity against citrullinated
protein (ACPA), in patients using glucocorticoids 0.36 times (95% CI 0.17-0.76). Despite that; in patients with chronic kidney disease, drug survival was
prolonged by 0.18 times (95% CI 0.06-0.57).
Conclusion: When starting biologic drugs in RA patients, some parameters may help to predict drug survival. According to the order of effect; while HBsAg
positivity, presence of hyperlipidemia, female gender, ACPA positivity, high ESR, advanced age and glucocorticoid use were negative markers for drug
survival; chronic kidney damage can be a positive marker.

Anahtar Kelimeler

Biological agents, Rheumatoid arthritis, Tumor necrosis factor

Kaynakça

• McInnes I. B, Schett G. Pathogenetic insights from thetreatment of rheumatoid arthritis. Lancet 2017;389:2328–2337.
• Scott DL, Wolfe F, Huizinga TWJ. Rheumatoid arthritis. Lancet 2010;376:1094–1108
• Lipsky PE. Romatoid artrit (çeviri: S. Akar). Akkoç N, Biberoğlu K. (Editörler). Harrison’s Principles of Internal Medicine Cilt 2. İstanbul: Nobel Tıp Kitabevleri; 2013.
• Smolen J. S, Aletaha D, Koeller M, Weisman M. H, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet 2007;370:1861–1874.
• Smolen J.S, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados et. al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. BMJ. 2017;76:960–977.
• Alptekin D. Ö. Romatizmal hastalıkların kullanılan biyolojik ajanlara güncel bakış. Bidder Tıp Bilimleri Dergisi, 2011;3(3):41-49.
• Keystone EC. Does anti-tumor necrosis factor-α therapy affect risk of serious infection and cancer in patients with rheumatoid arthritis?: a review of longterm data. J Rheumatol. 2011;38(8):1552-1562.
• Koncz T, Pentek M, Brodszky V, Ersek K, Orlewska E, Gulacsi L. Adherence to biologic DMARD therapies in rheumatoid arthritis. Expert Opin Biol Ther.2010;10(9):1367-11378.
• Leon L, Rodriguez LR, Rosales Z, Gomez A, Lamas JR, Pato E et. al. Long-term drug survival of biological agents in patients with rheumatoid arthritis in clinical practice. Scand J Rheumatol. 2016;45(6):456-460.
• Gulácsi L, Rencz F, Poór G, Szekanecz Z, Brodszky V, Baji P et.al. Patients' access to biological therapy in chronic inflammatory conditions; per capita GDP does not explain the intercountry differences. Ann Rheum Dis. 2016;75(5):942-943.
• Naffaa ME, Hassan F, Cohen AG, Merzon E, Green I , Saab 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.
• Desai RJ, Rao JK, Hansen RA, Fang G, Maciejewski ML, Farley JF. Predictors of treatment initiation with tumor necrosis factor-α inhibitors in patients with rheumatoid arthritis. J Manag Care Spec Pharm. 2014;20(11):1110-1120.
• Mahlich J, Sruamsiri R. Persistence with biologic agents for the treatment of rheumatoid arthritis in Japan. Patient Prefer Adherence. 2016;10:1509-1519.
• Souto A, Maneiro JR, Gómez-Reino JJ. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: A systematic review and meta-analysis of drug registries and health care databases. Rheumatology (Oxford). 2016;55(3):523-534.
• Min Jung S, Lee SW, Song JJ, Park SH, Park YB. Drug Survival of Biologic Therapy in Elderly Patients With Rheumatoid Arthritis Compared With Nonelderly Patients: Results From the Korean College of Rheumatology Biologics Registry. J Clin Rheumatol. 2022;28(1):81-88.
• Mathieu S, Pereira B, Saraux A, Richez C, Combe B, Soubrier M. Disease-modifying drug retention rate according to patient age in patients with early rheumatoid arthritis: Analysis of the ESPOIR cohort. Rheumatol Int. 2021;41(5):879-885.
• Marchesoni A, Zaccara E, Gorla R, Bazzani C, Sarzi-Puttini P, Atzeni F et. al. TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann N Y Acad Sci. 2009;1173:837-846.
• Markenson JA, Gibofsky A, Palmer WR, Keystone EC, Schiff MH, Feng J et. al. Persistence with anti-tumor necrosis factor therapies in patients with rheumatoid arthritis: observations from the RADIUS registry. J Rheumatol. 2011;38(7):1273-1281.
• Rubbert-Roth A, Szabó MZ, Kedves M, Nagy G, Atzeni F, Sarzi-Puttini P. Failure of anti-TNF treatment in patients with rheumatoid arthritis: The pros and cons of the early use of alternative biological agents. Autoimmun Rev. 2019;18(12):102398.
• Cho SK, Sung YK, Choi CB, Bae SC. Impact of comorbidities on TNF inhibitor persistence in rheumatoid arthritis patients: an analysis of Korean National Health Insurance claims data. Rheumatol Int. 2012;32(12):3851-3856.
• Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12(1):25-36.
• Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis. Cochrane Database Syst Rev. 2010;(7):CD008331.
• Alsulaim T, Alhassan N, Khalil H, Almutlaq A. Tocilizumab Effect on Lipid Profile in Correlation to Cardiovascular Events: A Retrospective Cohort Study. Int J Rheumatol. 2021;2021:5535486.
• Attar SM. Hyperlipidemia in rheumatoid arthritis patients in Saudi Arabia. Correlation with C-reactive protein levels and disease activity. Saudi Med J. 2015;36(6):685-691.
• Cho SK, Sung YK, Parkı S, Bae SC. Etanercept treatment in rheumatoid arthritis patients with chronic kidney failure on predialysis. Rheumatol Int. 2010;30(11):1519-1522.
• Don BR, Spin G, Nestorov I, Hutmacher M, Rose A, Kaysen GA. The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis. J Pharm Pharmacol. 2005;57(11):1407-1413.
• Riccio A, Tarantino G. Hepatitis C virus-related arthritis and rheumatoid arthritis: could they be different aspects of the same disease?. Int J Immunopathol Pharmacol. Jan-Mar 2012;25(1):293-296.
• Nakamura J, Nagashima T, Nagatani K, Yoshio T, Iwamoto M, Minota S. Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs. Int J Rheum Dis. 2016;19(5):470-475.
• Carlino G, Fornaro M, Santo L, Bucci R, Semeraro A, Quarta L et. al. Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE). Reumatismo. 2019;71(1):24-30.
• Zou CJ, Zhu LJ, Li YH, Mo YQ, Zheng DH, Ma JD et. al. The association between hepatitis B virus infection and disease activity, synovitis, or joint destruction in rheumatoid arthritis. Clin Rheumatol. 2013;32(6):787-795.
• Lin CT, Huang WN, Tsai WC, Chen JP, Hung WT, Hsieh TY et. al. Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis: Analysis from the TRA Clinical Electronic Registry. PLoS One. 2021;16(4):e0250877.
• Sellam J, Hendel-Chavez H, Rouanet S, Abbed K, Combe B, Loët XL et. al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63(4):933-938.
• Mulligen EV, Ahmed S, Weel AEAM, Hazes JMW, Mil AHMVDHV, Jong PHP. Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands. Clin Rheumatol. 2021;40(6):2177-2183.
• Han X, Lobo F, Broder MS, Chang E, Gibbs SN, Ridley DJ et. al. Persistence with Early-Line Abatacept versus Tumor Necrosis Factor-Inhibitors for Rheumatoid Arthritis Complicated by Poor Prognostic Factors. J Health Econ Outcomes Res. 2021;8(1):71-78.
• Flouri I, Markatseli TE, Voulgari PV, Boki KA, Papadopoulos I, Settas L, et. al. Comparative effectiveness and survival of infliximab, adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival. Semin Arthritis Rheum. 2014 Feb;43(4):447-457.
• Kristensen LE, Saxne T, Nilsson JA, Geborek P. Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden. Arthritis Res Ther. 2006;8(6):174.
• Du Pan SM, Dehler S, Ciurea A, Ziswiler HR, Gabay C, Finckh A. Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis. Arthritis Rheum. 2009;61(5):560-568.