Comorbidity Profile of Familial Mediterranean Fever Patients Varies by Treatments

Year 2025, Volume: 7 Issue: 1, 53 - 60, 25.02.2025

Esra Kayacan Erdoğan , Hakan Babaoglu , Şerife Coşkun , Rezan Koçak Ulucaköy , Kevser Orhan , Serdar Can Güven , Ebru Atalar , Bahar Özdemir Ulusoy , Hatice Ecem Konak , Pınar Akyüz Dağli , Özlem Karakaş , Hakan Apaydın , Bünyamin Polat , İsmail Doğan , Yüksel Maraş , Ahmet Omma , Orhan Küçükşahin , Şükran Erten , Berkan Armağan

https://doi.org/10.52827/hititmedj.1582847

Abstract

Objective: Comorbidities may have an impact on the patient’s quality of life and even survival. Treatment resistance in Familial Mediterranean Fever (FMF) may indirectly indicate severe disease, with inflammation-related comorbidities increasing as severity rises. In the literature, there are no sufficient studies regarding comorbidities in FMF patients. In this study, we aimed to evaluate the comorbid conditions of patients according to FMF treatment steps.
Material and Method: We retrospectively reviewed 740 patients with FMF treated at our rheumatology clinic between May 2019 and March 2024. Patient characteristics, comorbidities, and FMF treatments of patients were evaluated. Patients were grouped according to their FMF treatment: coated colchicine, compressed colchicine, and IL-1 inhibition. Patients received treatments aligned with their disease activity, in accordance with current reimbursement guidelines.
Results: The mean age (SD) of FMF patients was 40.7 (13.3) and 62.4% were female. Of the 44.7% all patients had at least one comorbidity. The three most common comorbidities are hypertension (20%), hyperlipidemia (7%), and depression (6.8%). The initial coated colchicine treatment was changed in a total of 24.5% to compressed colchicine, further step up was done in 13.2% patients to IL-1 inhibition. Hypertension and chronic kidney disease were more common in patients under IL-1 inhibitor treatment.
Conclusion: Our retrospective analysis shows that FMF patients, especially those in the IL-1 inhibitor group, frequently experience comorbidities like hypertension, hyperlipidemia, and depression, even though these patients are younger, suggesting a potential link to severe disease. A comprehensive evaluation of comorbidities, especially in severe disease, is essential to prevent complications, and improve quality of life.

Keywords

Colchicine, comorbidity, Familial Mediterranean Fever, hypertension.

Ethical Statement

The Ethics Committee of Ankara Bilkent City Hospital approved the study protocol (Date:06/09/2023 , Ethical approval number: E1-23-3897

Supporting Institution

Ankara Bilkent City Hospital

Project Number

E1-23-3897

Ailevi Akdeniz Ateşi Hastalarının Tedavilere Göre Değişen Komorbidite Profili

Abstract

Amaç: Komorbiditelerin hastanın yaşam kalitesi ve hatta sağkalımı üzerinde etkisi olabilir. Ailevi Akdeniz Ateşi (AAA) hastalarında tedaviye direnç/başarısızlık, şiddetli hastalığın dolaylı bir göstergesi olabilir. AAA hastalık şiddeti arttıkça, inflamasyon ve hasara bağlı komorbiditeler de artabilir. Literatürde AAA hastalarında, özellikle de tedaviye dirençli gruptaki erişkin hastalarda komorbiditelere ilişkin yeterli çalışma bulunmamaktadır. Bu çalışmada, AAA tedavi basamaklarına göre hastaların komorbid durumlarının değerlendirilmesi amaçlandı.
Gereç ve Yöntem: Mayıs 2019 ile Mart 2024 tarihleri arasında romatoloji kliniğimizde tedavi edilen 740 AAA hastası retrospektif olarak incelendi. Hastaların demografik özellikleri, komorbiditeleri, ailede AAA öyküsü ve AAA tedavileri değerlendirildi. Hastalar AAA tedavilerine göre kaplanmış kolşisin, sıkıştırılmış kolşisin ve IL-1 inhibitörü olmak üzere 3 gruba ayrıldı. Hastalar, mevcut geri ödeme kılavuzlarına uygun olarak hastalık aktiviteleri ile uyumlu tedaviler almıştır.
Bulgular: AAA hastalarının ortalama yaşı (SD) 40,7 (13,3) ve %62,4’ü kadındı. Hastaların %44,7’sinde en az bir komorbidite vardı. En sık görülen üç komorbidite hipertansiyon (%20), hiperlipidemi (%7) ve depresyondur (%6,8). Başlangıçtaki kaplanmış kolşisin tedavisi toplam %24,5 hastada sıkıştırılmış kolşisin olarak değiştirilmiş, %13,2 hastada ise IL-1 inhibisyonuna geçilmiştir. IL-1 inhibitörü tedavisi gören hastalarda hipertansiyon ve kronik böbrek hastalığı daha yaygındır.
Sonuç: Retrospektif analizimiz, AAA hastalarının, özellikle IL-1 inhibitörü grubundakilerin, daha genç olmalarına rağmen, hipertansiyon, hiperlipidemi ve depresyon gibi komorbiditeleri sıklıkla yaşadığını göstermektedir ve bu da şiddetli hastalık ve kronik inflamasyon arasında potansiyel bir bağlantı olduğunu düşündürmektedir. Özellikle şiddetli hastalığı olanlarda komorbiditelerin kapsamlı bir şekilde değerlendirilmesi, komplikasyonları önlemek ve yaşam kalitesini artırmak için gereklidir.

Keywords

Ailevi akdeniz ateşi, hipertansiyon, kolşisin, komorbidite

Ethical Statement

Çalışma protokolü Ankara Bilkent Şehir 1 Nolu Hastanesi Etik Kurulu tarafından onaylandı (Tarih: 06/09/2023, Etik onay numarası: E1-23-3897).

Project Number

E1-23-3897

References

• Alghamdi M. Familial Mediterranean fever, review of the literature. Clin Rheumatol 2017;36:1707-1713.
• Yesilada E, Savaci S, Yuksel S, Gulbay G, Otlu G, Kaygusuzoglu E. MEFV Mutations in Cases with Familial Mediterranean Fever (FMF). Annals of Medical Research 2021;12:235-238.
• Celebi ZK, Kucuksahin O, Sengul S, Tuzuner A, Keven K. Colchicine-resistant familial Mediterranean fever in a renal transplantation patient: successful treatment with anakinra. Clin Kidney J 2014;7:219-220.
• Parlar K, Ates MB, Egeli BH, Ugurlu S. The clinical role of anakinra in the armamentarium against familial Mediterranean fever. Expert Rev Clin Immunol 2024;20:441-453.
• Ozen S, Kone-Paut I, Gül A. Colchicine resistance and intolerance in familial Mediterranean fever: Definition, causes, and alternative treatments. Semin Arthritis Rheum 2017;47:115-120.
• Babaoglu H, Varan O, Kucuk H, et al. On demand use of anakinra for attacks of familial Mediterranean fever (FMF). Clin Rheumatol 2019;38:577-581.
• Vasi İ, Kardaş RC, Yıldırım D, et al. Is compressed colchicine tablet superior to other colchicine preparations in patients with familial Mediterranean fever? Int J Clin Pharmacol Ther 2024;62:77-82.
• İlgen U, Emmungil H, Küçükşahin O. Colchicine Intolerance: Does the Pharmaceutical Preparation Matter? Balkan Med J 2021;38:257-258.
• Öner N, Çelikel E, Tekin ZE, et al. Does switching from coated colchicine to compressed colchicine improve treatment response in patients with familial Mediterranean fever? Croat Med J 2023;64:354-361.
• Babaoglu H, Armagan B, Bodakci E, et al. Predictors of persistent inflammation in familial Mediterranean fever and association with damage. Rheumatology (Oxford) 2021;60:333-339.
• 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 Rheum Dis 2016;75:965-973.
• Hmamouchi I, Jaoude SB, Ziade N. Navigating comorbidities in chronic inflammatory rheumatic diseases: Insight and strategies. touchREVIEWS in RMD 2024;3(1):21-30.
• Balcı-Peynircioğlu B, Kaya-Akça Ü, Arıcı ZS, et al. Comorbidities in familial Mediterranean fever: analysis of 2000 genetically confirmed patients. Rheumatology (Oxford) 2020;59:1372-1380.
• Tezcan ME, Şen N, Yilmaz M, et al. The severity of FMF may be associated with co-morbidities. Annals of the Rheumatic Diseases 2020;79:1227-1228.
• Batu ED, Şener S, Arslanoglu Aydin E, et al. A score for predicting colchicine resistance at the time of diagnosis in familial Mediterranean fever: data from the TURPAID registry. Rheumatology (Oxford) 2024;63:791-797.
• Erden A, Batu ED, Sarı A, et al. Which definition should be used to determine colchicine resistance among patients with familial Mediterranean fever? Clin Exp Rheumatol 2018;36:97-102.
• Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci 2020;50:1591-1610.
• Coskun Benlidayi I. How effective and safe are the interventions reducing inflammation in familial Mediterranean fever? A Cochrane Review summary with commentary. Int J Rheum Dis 2020;23:1599-1601.
• Hmamouchi I, Paruk F, Tabra S, et al. Prevalence of glucocorticoid-induced osteoporosis among rheumatology patients in Africa: a systematic review and meta-analysis. Arch Osteoporos 2023;18:59.
• Turesson C. Comorbidity in rheumatoid arthritis. Swiss Med Wkly 2016;146:w14290.
• Yadav BS, Roy AN, Fatima SS. A cross-sectional study of different rheumatic diseases and their respective comorbidities at a tertiary care hospital in India. Indian Journal of Rheumatology 2019;14:42-48.
• Deger SM, Ozturk MA, Demirag MD, et al. Health-related quality of life and its associations with mood condition in familial Mediterranean fever patients. Rheumatol Int 2011;31:623-628.
• El-Shanti HI. Familial Mediterranean fever and renal disease. Saudi J Kidney Dis Transpl 2003;14:378-385.
• Touitou I, Sarkisian T, Medlej-Hashim M, et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum 2007;56:1706-1712.
• Zhang Z, Zhao L, Zhou X, Meng X, Zhou X. Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Front Immunol 2023;13:1098725.
• Pietri P, Vlachopoulos C, Tousoulis D. Inflammation and arterial hypertension: From pathophysiological links to risk prediction. Curr Med Chem 2015;22:2754-2761.
• Mallamaci F, Tripepi G. Risk factors of chronic kidney disease progression: Between old and new concepts. Journal of Clinical Medicine 2024;13:678.
• Siasos G, Tousoulis D, Oikonomou E, Zaromitidou M, Stefanadis C, Papavassiliou AG. Inflammatory markers in hyperlipidemia: from experimental models to clinical practice. Curr Pharm Des 2011;17:4132-4146.
• Lira FS, Rosa Neto JC, Antunes BM, Fernandes RA. The relationship between inflammation, dyslipidemia, and physical exercise: from the epidemiological to molecular approach. Curr Diabetes Rev 2014;10:391-396.
• Papoutsidakis N, Deftereos S, Giannopoulos G, Panagopoulou V, Manolis AS, Bouras G. Treating dyslipidemias: is inflammation the missing link? Med Chem 2014;10:643-652.
• Almond M. Depression and inflammation: examining the link. Current Psychiatry 2013;12:24-32.
• Kiecolt-Glaser JK, Derry HM, Fagundes CP. Inflammation: depression fans the flames and feasts on the heat. Am J Psychiatry 2015;172:1075-1092.
• Sag S, Sag M, Tekeoglu I, Kamanli A, Nas K. Frequency of depression, anxiety, and fatigue in FMF patients and their association with disease parameters. Medicine 2018;7:773-776.
• Durcan G, Yildiz M, Kadak MT, et al. Increased frequency of sleep problems in children and adolescents with familial Mediterranean fever: The role of anxiety and depression. Int J Rheum Dis 2020;23:1396-1403.
• Suticen E, Atas N, Guler AA, et al. Work productivity impairment in patients with familial Mediterranean fever and effects of interleukin-1 antagonists. Clin Rheumatol 2021;40:2865-2871.