Impact of colchicine on inflammatory markers and pregnancy outcomes in familial Mediterranean fever patients

Abstract

Objectives: The aim of this study is to evaluate the effect of colchicine use on maternal inflammatory markers and pregnancy outcomes in pregnant women diagnosed with Familial Mediterranean Fever (FMF) and receiving colchicine therapy.

Methods: This retrospective analysis included 42 pregnant women diagnosed with FMF who underwent colchicine treatment and 126 healthy pregnant controls. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR), and Monocyte/Lymphocyte Ratio (MLR) rates in the blood of the groups in the first trimester, obstetric morbidities and pregnancy outcomes were compared.

Results: The patient cohort had markedly reduced hemoglobin levels (12.15±1.36 vs. 12.80±1.02 g/dL, P=0.001), an elevated prevalence of anemia (19% vs. 3%, P=0.002), and diminished monocyte counts (0.55 vs. 0.61 ×10⁹/L, P=0.022) as well as decreased MLR values (0.27 vs. 0.29, P=0.020) in comparison to the control group. Other inflammatory markers, pregnancy complications, and neonatal outcomes were similar between the groups (p>0.05).

Conclusions: Colchicine seems to be useful in managing inflammation during FMF pregnancies without negatively affecting pregnancy or neonatal outcomes. Thorough prenatal care, encompassing anemia monitoring, is crucial for enhancing mother and fetal health.

Keywords

• Familial Mediterranean fever
• colchicine
• inflammation
• pregnancy

References

1. 1. Chaaban A, Salman Z, Karam L, Kobeissy PH, Ibrahim JN. Updates on the role of epigenetics in familial mediterranean fever (FMF). Orphanet J Rare Dis. 2024;19(1):90. doi: 10.1186/s13023-024-03098-w.
2. 2. Davidson A, Kuller JA, Dotters-Katz SK, Wood RL. Familial Mediterranean Fever in Pregnancy. Obstet Gynecol Surv. 2024;79(10):611-616. doi: 10.1097/OGX.0000000000001316.
3. 3. Hirahara Y, Yamaguchi M, Takase-Minegishi K, et al. Pregnancy outcomes in patients with familial Mediterranean fever: systematic review and meta-analysis. Rheumatology (Oxford). 2024;63(2):277-284. doi: 10.1093/rheumatology/kead417.
4. 4. Yasar O, Iskender C, Kaymak O, Taflan Yaman S, Uygur D, Danisman N. Retrospective evaluation of pregnancy outcomes in women with familial Mediterranean fever. J Matern Fetal Neonatal Med. 2014;27(7):733-736. doi: 10.3109/14767058.2013.837446.
5. 5. Leung YY, Yao Hui LL, Kraus VB. Colchicine--Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45(3):341-350. doi: 10.1016/j.semarthrit.2015.06.013.
6. 6. Rech J, Schett G, Tufan A, et al. Patient Experiences and Challenges in the Management of Autoinflammatory Diseases-Data from the International FMF & AID Global Association Survey. J Clin Med. 2024;13(5):1199. doi: 10.3390/jcm13051199.
7. 7. Indraratna PL, Virk S, Gurram D, Day RO. Use of colchicine in pregnancy: a systematic review and meta-analysis. Rheumatology (Oxford). 2018;57(2):382-387. doi: 10.1093/rheumatology/kex353.
8. 8. Atalay A, Yetiskin FDY, Ocal FD, Besimoglu B, Kucuksahin O, Sahin D. First and second-trimester biochemical serum markers in maternal familial Mediterranean fever: The impact of colchicine use. J Gynecol Obstet Hum Reprod. 2023;52:102648. doi: 10.1016/j.jogoh.2023.102648.

9. 9. Zhang D, Zeng Y, Sun B, et al. Inflammatory indices—Systemic Immune-Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI)-during Pregnancy and Associations with Gestational Diabetes Mellitus. J Inflamm Res. 2024;17:6521-6532. doi: 10.2147/JIR.S474154
10. 10. Gulseren V, Daggez M, Sen E, et al. The Effect of Prognostic Nutritional Index and Systemic Inflammatory Index in Endometrioid Type Endometrial Cancer. Gynecol Obstet Reprod Med. 2024;30(3):198-205. doi: 10.21613/GORM.2023.1490.
11. 11. Karabay G, Bayraktar B, Seyhanli Z, et al. Predictive value of inflammatory markers (NLR, PLR, MLR, SII, SIRI, PIV, IG, and MII) for latency period in Preterm premature rupture of membranes (PPROM) pregnancies. BMC Pregnancy Childbirth. 2024;24(1):564. doi: 10.1186/s12884-024-06756-w.
12. 12. Sahin R, Tanacan A, Serbetci H, et al. The Association of Systemic Immune-Inflammation Index (SII), Systemic Immune-Response Index (SIRI), and Neutrophil-to-Lymphocyte Ratio (NLR) with Cesarean Scar Pregnancy (CSP). J Reprod Immunol. 2024;164:104275. doi: 10.1016/j.jri.2024.104275.
13. 13. Karagun S, Dal Y, Yildiz H, et al. First-Trimester Threatened Abortion: Can Red Blood Cell Distribution Width-Standard Deviation Predict Miscarriage?. Gynecol Obstet Reprod Med. 2024;30(3):152-158. doi: 10.21613/GORM.2023.1489.
14. 14. Özen S, Batu ED, Demir S. Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. Front Immunol. 2017;8:253. doi: 10.3389/fimmu.2017.00253.
15. 15. Cerquaglia C, Diaco M, Nucera G, Regina ML, Montalto M, Manna R. Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update. Curr Drug Targets Inflamm Allergy. 2005;4(1):117-124.
16. 16. Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology. 2006;45(3):274-282. doi: 10.1093/rheumatology/kei140.
17. 17. Doğan M, Boyacıoğlu M, Doğan AG. Evaluation of neutrophyl/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume according to the disease activity index in patients of ankylosing spondylitis. J Health Sci Med. 2022;5(1):247-251. doi: 10.32322/jhsm.1012686.
18. 18. Song A, Eo W, Lee S. Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients. World J Gastroenterol. 2015;21(43):12410-12420. doi: 10.3748/wjg.v21.i43.12410.
19. 19. Meyer-Lindemann U, Mauersberger C, Schmidt AC, et al. Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation. Front Immunol. 2022;13:898690. doi: 10.3389/fimmu.2022.898690.
20. 20. Gazzito Del Padre TC, Belem JMFM, de Aguiar MF, et al. Distribution of monocytes subpopulations in the peripheral blood from patients with Behçet's disease - Impact of disease status and colchicine use. Clin Immunol. 2021;231:108854. doi: 10.1016/j.clim.2021.108854.
21. 21. Celkan T, Celik M, Kasapçopur O, et al. The anemia of familial Mediterranean fever disease. Pediatr Hematol Oncol. 2005;22(8):657-665. doi: 10.1080/08880010500278681.
22. 22. Berkenstadt M, Weisz B, Cuckle H, Di-Castro M, Guetta E, Barkai G. Chromosomal abnormalities and birth defects among couples with colchicine treated familial Mediterranean fever. Am J Obstet Gynecol. 2005;193(4):1513-1516. doi: 10.1016/j.ajog.2005.03.043.
23. 23. Ehrenfeld M, Brzezinski A, Levy M, Eliakim M. Fertility and obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynaecol. 1987;94(12):1186-1191. doi: 10.1111/j.1471-0528.1987.tb02320.x.
24. 24. Mijatovic V, Hompes PG, Wouters MG. Familial Mediterranean fever and its implications for fertility and pregnancy. Eur J Obstet Gynecol Reprod Biol. 2003;108(2):171-176. doi: 10.1016/s0301-2115(02)00417-7.
25. 25. Sotskiy PO, Sotskaya OL, Hayrapetyan HS, et al. Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever and Controls. J Rheumatol. 2021;48(4):608-614. doi: 10.3899/jrheum.200574.
26. 26. Ofir D, Levy A, Wiznitzer A, Mazor M, Sheiner E. Familial Mediterranean fever during pregnancy: an independent risk factor for preterm delivery. Eur J Obstet Gynecol Reprod Biol. 2008;141(2):115-118. doi: 10.1016/j.ejogrb.2008.07.025.