Antireumatski lekovi koji modificiraju bolest usporavaju reumatoidni artritis analizom upalnih markera: povezanost s razvojem sideropenije i anemije hronične bolesti
Ključne reči:
Reumatoidni artritis; Anti-CCP; C reaktivni protein; Metotrexat
Sažetak
Uvod/Cilj. Reumatoidni artritis (RA) je sistemska autoimuna bolest koja može uzrokovati destruktivnu bolest zglobova i progresivni invaliditet. Dijagnostika RA se zasniva na laboratorijskim i kliničkim dokazima koji obuhvataju analizu upalnih markera, hematoloških i biohemijskih parametara.
Metode. Pedeset pacijenata sa dijagnozom RA bez terapije i 50 pacijenata sa terapijom (metotreksat, 12 mg/sedmično; nakon tri meseca prednizolon 10 mg/dnevno) su uključeni u ovu studiju. Nakon šestomesečne terapije analizirani su upalni markerin, hematološki i biohemijski parametri.
Rezultati. Inflamatorni markri (SE, CRP-a i Anti-CCP) su signifikantno niži u grupi pacijenata na terapiji u odnosu na pacijente bez terapije. Nisu utvrđene značajne razlike za reuma faktor RF. Između kompariranih grupa nisu utvrđene signifikantne razlike za hematološke parametre. Analiza serumskih biohemijskih parametara pokazala je signifikantne razlike za AST i željezo. Kod pacijenata bez terapije incidenca anemije je zabilježena kod 68%, što je značajno više u odnosu incidencu od 32% kod pacijenata sa uključenom terapijom. Anemija hronične bolesti i sideropenijska anemija su dva najčešća tipa anemije zastupljena kod RA pacijenata.
Zaključak. Ordinirana terapija pokazala je efikasnost u lečenju RA i redukciji inflamatornog procesa. Uspešnost lečenja zavisi od pravovremen dijagnoze RA; odlaganje terapije i kasno detektovana bolest produžava tretman terapije i često zaheva kombinaciju više lekova.
Reference
1. Shakeel S, Iffat W, Qamar A et al. Healthcare professionals' compliance with the standard management guidelines towards the use of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients. Int J Environ Res Public Health 2022;19(8):4699. https://doi.org/10.3390/ijerph19084699
2. Dans LF, Tankeh-Torres S, Amante CM et al. The prevalence of rheumatic diseases in a Filipino urban population: a WHO-ILAR COPCORD Study. World Health Organization. International League of Associations for Rheumatology. Community Oriented Programme for the Control of the Rheumatic Diseases. J Rheumatol 1997;24(9):1814-1819.
3. Guo Q, Wang Y, Xu D et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res 2018;6:15. https://doi.org/10.1038/s41413-018-0016-9
4. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365(23):2205-2219. https://doi.org/10.1056/NEJMra1004965
5. Chaudhari K, Rizvi S, Syed BA. Rheumatoid arthritis: current and future trends. Nat Rev Drug Discov 2016;15(5):305-306. https://doi.org/10.1038/nrd.2016.21
6. Cho SK, Kim D, Won S et al. Factors associated with time to diagnosis from symptom onset in patients with early rheumatoid arthritis. Korean J Intern Med 2019;34(4):910-916. https://doi.org/10.3904/kjim.2017.113
7. Moura CS, Abrahamowicz M, Beauchamp ME et al. Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study. Arthritis Res Ther 2015;17(1):197. https://doi.org/10.1186/s13075-015-0713-3
8. Bullock J, Rizvi SAA, Saleh AM et al. Rheumatoid arthritis: A brief overview of the treatment. Med Princ Pract 2018;27(6):501-507. https://doi.org/10.1159/000493390
9. Rein P, Mueller RB. Treatment with Biologicals in Rheumatoid Arthritis: An Overview. Rheumatol Ther 2017;4(2):247-261. https://doi.org/10.1007/s40744-017-0073-3
10. Smolen JS, Aletaha D, Barton A et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018;4:18001. https://doi.org/10.1038/nrdp.2018.1
11. den Broeder AA, van Herwaarden N, van den Bemt BJF. Therapeutic drug monitoring of biologicals in rheumatoid arthritis: a disconnect between beliefs and facts. Curr Opin Rheumatol 2018;30(3):266-275. https://doi.org/10.1097/BOR.0000000000000487
12. Tovey MG, Lallemand C. Immunogenicity and other problems associated with the use of biopharmaceuticals. Ther Adv Drug Saf 2011;2(3):113-128. https://doi.org/10.1177/2042098611406318
13. Choy EH, Smith C, Doré CJ et al. A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal. Rheumatol 2005;44(11):1414-1421. https://doi.org/10.1093/rheumatology/kei031
14. Volin MV, Harlow LA, Woods JM et al. Treatment with sulfasalazine or sulfapyridine. but not 5-aminosalicyclic acid. inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis. Arthritis Rheum 1999;42(9):1927-1935. https://doi.org/10.1002/1529-0131(199909)42:9<1927::AID-ANR19>3.0.CO;2-X
15. Tian H, Cronstein BN. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bull NYU Hosp Jt Dis 2007;65(3):168-173.
16. van der Linden MP, le Cessie S, Raza K et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum 2010;62(12):3537-3546. https://doi.org/10.1002/art.27692
17. Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev 2012;18(1):CD008921. https://doi.org/10.1002/14651858.CD008921
18. Shrivastava AK, Singh HV, Raizada A et al. Inflammatory markers in patients with rheumatoid arthritis. Allergol Immunopathol (Madr) 2015;43(1):81-87. https://doi.org/10.1016/j.aller.2013.11.003
19. Ruof J, Hülsemann JL, Mittendorf T et al. Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer's data sources. Ann Rheum Dis 2003;62(6):544-549. https://doi.org/10.1136/ard.62.6.544
20. Alessandri C, Bombardieri M, Papa N et al. Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann Rheum Dis 2004;63(10):1218-1221. https://doi.org/10.1136/ard.2003.014647
21. Cohen S, Hurd E, Cush J et al. Treatment of rheumatoid arthritis with anakinra. a recombinant human interleukin-1 receptor antagonist. in combination with methotrexate: results of a twenty-four-week. Multicenter, randomized, double-blind. placebo-controlled trial. Arthritis Rheum 2002;46(3):614-624. https://doi.org/10.1002/art.10141
22. Maini RN, Breedveld FC, Kalden JR et al. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. Sustained improvement over two years in physical function. structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 2004;50(4):1051-1065. https://doi.org/10.1002/art.20159
23. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009;68(7):1094-1099. https://doi.org/10.1136/ard.2008.092668
24. Gutierrez-Ureña S, Molina JF, García CO et al. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum 1996;39(2):272-276. https://doi.org/10.1002/art.1780390214
25. Gerards AH, de Lathouder S, de Groot ER et al. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatol 2003;42(10):1189-1196. https://doi.org/10.1093/rheumatology/keg323
26. Dalrymple JM, Stamp LK, O'Donnell JL et al. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2008;58(11):3299-3308. https://doi.org/10.1002/art.24034
27. Dechanuwong P, Phuan-Udom R. Hematological parameters as a predictor of disease remission in patients with rheumatoid arthritis. Ann Med Surg (Lond) 2021;72:103085. https://doi.org/10.1016/j.amsu.2021.103085
28. Ganz T. Anemia of inflammation. N Engl J Med 2019;381(12):1148-1157. https://doi.org/10.1056/NEJMra1804281
29. Kounis NG, Soufras GD, Tsigkas G et al. White blood cell counts. leukocyte ratios. and eosinophils as inflammatory markers in patients with coronary artery disease. Clin Appl Thromb Hemost 2015;21(2):139-143. https://doi.org/10.1177/1076029614531449
30. Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol 2012;590(5):1023-1034. https://doi.org/10.1113/jphysiol.2011.225417
31. Talukdar M, Barui G, Adhikari A et al. A Study on Association between common haematological parameters and disease activity in rheumatoid arthritis. J Clin Diagn Res 2017;11(1):EC01-EC04. https://doi.org/10.7860/JCDR/2017/23524.9130
32. Işık M, Şahin H, Hüseyin E. New platelet indices as inflammatory parameters for patients with rheumatoid arthritis. Eur J Rheumatol 2014;1(4):144-146. https://doi.org/ 10.5152/eurjrheumatol.2014.140023
33. Tekeoğlu İ, Gürol G, Harman H et al. Overlooked hematological markers of disease activity in rheumatoid arthritis. Int J Rheum Dis 2016;19(11):1078-1082. https://doi.org/10.1111/1756-185X.12805
34. Chandrashekara S, Rajendran A, Bai Jaganath A et al. Neutrophil-lymphocyte ratio. pain perception. and disease activity score may serve as important predictive markers for sustained remission in rheumatoid arthritis. Reumatismo 2015;67(3):109-115. https://doi.org/10.4081/reumatismo.2015.838
35. Kremer JM, Alarcón GS, Willkens RF et al. Methotrexate for rheumatoid arthritis. Arthritis Rheumatol 1994;37(3):316-328. https://doi.org/10.1002/art.1780370304
36. Karsdal MA, Henriksen K, Leeming DJ et al. Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers 2009;14(3):181-202. https://doi.org/10.1080/13547500902777608
37. Pallinti V, Ganesan N, Anbazhagan M et al. Serum biochemical markers in rheumatoid arthritis. Indian J Biochem Biophys 2009;46(4):342-344
38. Smith RJ, Davis P, Thomson AB et al. Serum ferritin levels in anemia of rheumatoid arthritis. J Rheumatol 1977;4(4):389-392.
39. Peeters HR, Jongen-Lavrencic M, Raja AN et al. Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset. Ann Rheum Dis 1996;55(3):162-168. https://doi.org/10.1136/ard.55.3.162
2. Dans LF, Tankeh-Torres S, Amante CM et al. The prevalence of rheumatic diseases in a Filipino urban population: a WHO-ILAR COPCORD Study. World Health Organization. International League of Associations for Rheumatology. Community Oriented Programme for the Control of the Rheumatic Diseases. J Rheumatol 1997;24(9):1814-1819.
3. Guo Q, Wang Y, Xu D et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res 2018;6:15. https://doi.org/10.1038/s41413-018-0016-9
4. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365(23):2205-2219. https://doi.org/10.1056/NEJMra1004965
5. Chaudhari K, Rizvi S, Syed BA. Rheumatoid arthritis: current and future trends. Nat Rev Drug Discov 2016;15(5):305-306. https://doi.org/10.1038/nrd.2016.21
6. Cho SK, Kim D, Won S et al. Factors associated with time to diagnosis from symptom onset in patients with early rheumatoid arthritis. Korean J Intern Med 2019;34(4):910-916. https://doi.org/10.3904/kjim.2017.113
7. Moura CS, Abrahamowicz M, Beauchamp ME et al. Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study. Arthritis Res Ther 2015;17(1):197. https://doi.org/10.1186/s13075-015-0713-3
8. Bullock J, Rizvi SAA, Saleh AM et al. Rheumatoid arthritis: A brief overview of the treatment. Med Princ Pract 2018;27(6):501-507. https://doi.org/10.1159/000493390
9. Rein P, Mueller RB. Treatment with Biologicals in Rheumatoid Arthritis: An Overview. Rheumatol Ther 2017;4(2):247-261. https://doi.org/10.1007/s40744-017-0073-3
10. Smolen JS, Aletaha D, Barton A et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018;4:18001. https://doi.org/10.1038/nrdp.2018.1
11. den Broeder AA, van Herwaarden N, van den Bemt BJF. Therapeutic drug monitoring of biologicals in rheumatoid arthritis: a disconnect between beliefs and facts. Curr Opin Rheumatol 2018;30(3):266-275. https://doi.org/10.1097/BOR.0000000000000487
12. Tovey MG, Lallemand C. Immunogenicity and other problems associated with the use of biopharmaceuticals. Ther Adv Drug Saf 2011;2(3):113-128. https://doi.org/10.1177/2042098611406318
13. Choy EH, Smith C, Doré CJ et al. A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal. Rheumatol 2005;44(11):1414-1421. https://doi.org/10.1093/rheumatology/kei031
14. Volin MV, Harlow LA, Woods JM et al. Treatment with sulfasalazine or sulfapyridine. but not 5-aminosalicyclic acid. inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis. Arthritis Rheum 1999;42(9):1927-1935. https://doi.org/10.1002/1529-0131(199909)42:9<1927::AID-ANR19>3.0.CO;2-X
15. Tian H, Cronstein BN. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bull NYU Hosp Jt Dis 2007;65(3):168-173.
16. van der Linden MP, le Cessie S, Raza K et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum 2010;62(12):3537-3546. https://doi.org/10.1002/art.27692
17. Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev 2012;18(1):CD008921. https://doi.org/10.1002/14651858.CD008921
18. Shrivastava AK, Singh HV, Raizada A et al. Inflammatory markers in patients with rheumatoid arthritis. Allergol Immunopathol (Madr) 2015;43(1):81-87. https://doi.org/10.1016/j.aller.2013.11.003
19. Ruof J, Hülsemann JL, Mittendorf T et al. Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer's data sources. Ann Rheum Dis 2003;62(6):544-549. https://doi.org/10.1136/ard.62.6.544
20. Alessandri C, Bombardieri M, Papa N et al. Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann Rheum Dis 2004;63(10):1218-1221. https://doi.org/10.1136/ard.2003.014647
21. Cohen S, Hurd E, Cush J et al. Treatment of rheumatoid arthritis with anakinra. a recombinant human interleukin-1 receptor antagonist. in combination with methotrexate: results of a twenty-four-week. Multicenter, randomized, double-blind. placebo-controlled trial. Arthritis Rheum 2002;46(3):614-624. https://doi.org/10.1002/art.10141
22. Maini RN, Breedveld FC, Kalden JR et al. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. Sustained improvement over two years in physical function. structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 2004;50(4):1051-1065. https://doi.org/10.1002/art.20159
23. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009;68(7):1094-1099. https://doi.org/10.1136/ard.2008.092668
24. Gutierrez-Ureña S, Molina JF, García CO et al. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum 1996;39(2):272-276. https://doi.org/10.1002/art.1780390214
25. Gerards AH, de Lathouder S, de Groot ER et al. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatol 2003;42(10):1189-1196. https://doi.org/10.1093/rheumatology/keg323
26. Dalrymple JM, Stamp LK, O'Donnell JL et al. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2008;58(11):3299-3308. https://doi.org/10.1002/art.24034
27. Dechanuwong P, Phuan-Udom R. Hematological parameters as a predictor of disease remission in patients with rheumatoid arthritis. Ann Med Surg (Lond) 2021;72:103085. https://doi.org/10.1016/j.amsu.2021.103085
28. Ganz T. Anemia of inflammation. N Engl J Med 2019;381(12):1148-1157. https://doi.org/10.1056/NEJMra1804281
29. Kounis NG, Soufras GD, Tsigkas G et al. White blood cell counts. leukocyte ratios. and eosinophils as inflammatory markers in patients with coronary artery disease. Clin Appl Thromb Hemost 2015;21(2):139-143. https://doi.org/10.1177/1076029614531449
30. Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol 2012;590(5):1023-1034. https://doi.org/10.1113/jphysiol.2011.225417
31. Talukdar M, Barui G, Adhikari A et al. A Study on Association between common haematological parameters and disease activity in rheumatoid arthritis. J Clin Diagn Res 2017;11(1):EC01-EC04. https://doi.org/10.7860/JCDR/2017/23524.9130
32. Işık M, Şahin H, Hüseyin E. New platelet indices as inflammatory parameters for patients with rheumatoid arthritis. Eur J Rheumatol 2014;1(4):144-146. https://doi.org/ 10.5152/eurjrheumatol.2014.140023
33. Tekeoğlu İ, Gürol G, Harman H et al. Overlooked hematological markers of disease activity in rheumatoid arthritis. Int J Rheum Dis 2016;19(11):1078-1082. https://doi.org/10.1111/1756-185X.12805
34. Chandrashekara S, Rajendran A, Bai Jaganath A et al. Neutrophil-lymphocyte ratio. pain perception. and disease activity score may serve as important predictive markers for sustained remission in rheumatoid arthritis. Reumatismo 2015;67(3):109-115. https://doi.org/10.4081/reumatismo.2015.838
35. Kremer JM, Alarcón GS, Willkens RF et al. Methotrexate for rheumatoid arthritis. Arthritis Rheumatol 1994;37(3):316-328. https://doi.org/10.1002/art.1780370304
36. Karsdal MA, Henriksen K, Leeming DJ et al. Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers 2009;14(3):181-202. https://doi.org/10.1080/13547500902777608
37. Pallinti V, Ganesan N, Anbazhagan M et al. Serum biochemical markers in rheumatoid arthritis. Indian J Biochem Biophys 2009;46(4):342-344
38. Smith RJ, Davis P, Thomson AB et al. Serum ferritin levels in anemia of rheumatoid arthritis. J Rheumatol 1977;4(4):389-392.
39. Peeters HR, Jongen-Lavrencic M, Raja AN et al. Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset. Ann Rheum Dis 1996;55(3):162-168. https://doi.org/10.1136/ard.55.3.162
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2025/11/19
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Originalni rad / Original article