Investigating the Causes and Incidence of Mortality in Patients Using Biological Disease Modifying Antirheumatic Drug (DMARD) and the Mortality Rates Thereof Compared to the General Population

Öz

AIM: Disease-modifying antirheumatic drugs (DMARDs) are used in the treatment of most rheumatological diseases (1). There is a number of studies availabile in the literature, in which the effect of DMARDs on mortality has been investigated; however these studies were generally performed on rheumatoid arthritis (RA), and on tumor necrosis factor inhibitors (TNFi) in particular (2-5). Hence, we aimed to conduct a more comprehensive study investigating the effects of using abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, secukinumab, tofacitinib and tocilizumab on mortality in patients with RA, ankylosing spondylitis (AS), psoriatic arthritis (PsA), Behçet's disease, systemic lupus erythematosus (SLE), Takayasu's arteritis, systemic sclerosis (SSc), Sjogren's syndrome and other rheumatological diseases. MATERIAL AND METHOD: 847 patients that have used bDMARDs were included in our study. Age, gender, diagnosis and treatment information of these patients were retrospectively scanned and recorded. Death records were obtained from the National Death Notification Service (6), whereas the population records were obtained from the Turkish Statistical Institute (7). bDMARD-related incidence rates (IRs) for mortality was calculated. RESULTS: A total of 847 patients, 464 (54.8%) of whom were female and 383 (45.2%) of whom were male, were included in the study. Mortality occurred in a total of 18 patients (2.1%) during the treatment process. Of these 18 patients, 5 patients were using rituximab, 4 patients were using infliximab, 3 patients were using adalimumab, 3 patients were using etanercept, 2 patients were using tocilizumab, and 1 patient were using golimumab. In terms of the mortalities by the type of diagnosis, 13 mortalities occurred in the group of patients diagnosed with RA, whereas 1 mortality occurred in each of the groups consisting of patients diagnosed with AS, PsA, Takayasu arteritis, granulomatosis with polyangiitis (Wegener) or SSc. The overall mortality incidence of the patients was calculated as 5.28 cases per 1000 years. Compared to the general population, the standardized mortality ratio (SMR) of the patients using bDMARDs was found to be 3.147 ((confidence interval (CI): 1.924-4.877)). CONCLUSIONS: Our study is the first mortality study conducted in Turkey on patients with rheumatologic disease that use bDMARDs. The incidence rate (IR) for mortality we have found in patients using bDMARDs was comparable to the IRs reported in the literature, however we have found a higher standart mortalie ratio (SMR) in our cohort compared to the Turkish population. In this respect, it is necessary to conduct larger-scale controlled studies.

Anahtar Kelimeler

• Antirheumatic agents
• mortality
• rheumatic diseases

Biyolojik Hastalık Modifiye Edici Antiromatizmal İlaç (bDMARD) Kullanan Hastaların Mortalite Nedenlerinin, Mortalite İnsidanslarının ve Genel Topluma Oranla Mortalite Oranlarının Araştırılması

Öz

AMAÇ: Romatolojik hastalıkların çoğunun tedavisinde hastalık modifiye edici antiromatizmal İlaç (DMARD) kullanılmaktadır (1). Literatürde yapılan çalışmalarda DMARD’ların mortalite üzerine etkisi araştırılmış fakat bu çalışmalar genellikle romatoid artritte (RA) ve genellikle tümör nekroz faktör inhibitörlerinin (TNFi) üzerinde yapılmıştır (2-5). Biz ise daha kapsamlı olarak RA, ankilozan spondilit (AS), psöriatik artrit (PsA), Behçet hastalığı, sistemik lupus eritematozus (SLE), Takayasu arteriti, sistemik skleroz (SSc), Sjogren sendromu ve diğer romatolojik hastalıklarda abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, secukinumab, tofacitinib ve tocilizumab kullanımının mortalite üzerine etkisini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Çalışmamıza bDMARD kullanan 847 hasta alındı. Hastaların yaş, cinsiyet, tanı, tedavi verileri retrospektif olarak taranıp kayıt edildi. Ölüm kayıtları Ulusal Ölüm Bildirim Sistemi’nden (6) nüfus kayıtları Türkiye İstatistik Kurumu’ndan (7) alındı. bDMARD ilişkili mortalite insidans oranları hesaplandı. BULGULAR: Çalışmaya 464 (54.8%) kadın, 383 (45.2%) erkek olmak üzere toplam 847 hasta alındı. Tedavi sürecinde rituximab, infliximab, adalimumab, etanercept, golimumab ve tocilizumab kullanan hastalarda (sırasıyla; 5, 4, 3, 3, 1, 2) olmak üzere toplam 18 hastada (%2.1) mortalite gerçekleşti. Tanıya göre bakıldığında RA, AS, PsA, Takayasu arteriti, granülomatozisli polianjitis (Wegener granülomatozis), SSc tanılı hastalarda mortalite gerçekleşti (sırasıyla; 13, 1, 1, 1, 1, 1). Hastaların genel mortalite insidansı 1000 hasta yılında 5,28 vaka olarak tespit edildi. Genel nüfusa oranla bDMARD kullanan hastaların standart ölüm oranı (SMR) 3.147 (CI:1.924-4.877) olarak saptandı. SONUÇ: Çalışmamız Türkiye’deki bDMARD kullanıp romatolojik hastalığı olan hastalarda yapılan ilk mortalite çalışmasıdır. Çalışmamızda genel olarak bDMARD kullanan hastalarda literatüre benzer bir mortalite insidans oranı tespit ettik fakat kohortumuzda Türk toplumuna göre yüksek bir SMR saptadık. Bu açıdan daha geniş ölçekli, kontrol gruplu çalışmaların yapılmasına ihtiyaç vardır.

Anahtar Kelimeler

• Antiromatizmal ajanlar
• mortalite
• romatizmal hastalıklar

Kaynakça

1. Smolen JS, Landewe 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;79:685-99.
2. Poiroux L, Allanore Y, Kahan A et al. All-cause Mortality Associated with TNF-alpha Inhibitors in Rheumatoid Arthritis: A Meta-Analysis of Randomized Controlled Trials. Am J Med. 2015;128:1367-73 e1.
3. Herrinton LJ, Liu L, Chen L et al. Association between anti-TNF-alpha therapy and all-cause mortality. Pharmacoepidemiol Drug Saf. 2012;21:1311-20.
4. Jacobsson LT, Turesson C, Nilsson JA et al. Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:670-5.
5. Listing J, Kekow J, Manger B et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Ann Rheum Dis. 2015;74:415-21.
6. Ölüm Bildirim Sistemi[https://obs.saglik.gov.tr/Account/Login]
7. Türkiye İstatistik Kurumu [https://www.tuik.gov.tr/tr/#]