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The Comparison of Treatment Results of Rheumatoid Arthritis with DMARDs and Anti TNF Drugs Based on the Disease Activity and Remission Criteria

Year 2020, Volume: 7 Issue: 1, 6 - 11, 28.04.2020

Türkan Turgay Ali Aydeniz Savaş Gürsoy

Abstract

We aimed to compare the effectiveness of DMARD (Disease Modifying Anti-Rheumatismal Drug) drugs and methotrexate combined anti-TNF (Tumor Necrosis Factor) treatment on disease activity criteria in preventing or controlling joint damage in rheumatoid arthritis (RA). Seventy-five active RA patients followed for 24 weeks were included in the study. The demographic features, DAS28 (Disease Activity Score), VAS (Visual Analogue Scale), HAQ (Health Assessment Questionnaire) parameters and laboratory values were recorded from their files retrospectively. Patients were divided into two groups: 37 receiving anti-TNF (infliximab, etanercept, adalimumab) combined with methotrexate and 38 receiving DMARD (leflunomide+methotrexate, sulfasalacin+methotrexate, methotrexate only). The therapeutic efficacy was evaluated by American College of Rheumatology (ACR) 20, 50 and 70 criteria. The mean age of patients using combined anti-TNF drug and DMARD was 50.27±7.9 and 46.79±8.6, respectively. There was a statistically significant difference between the groups only in HAQ score before treatment. Pre- and post-treatment parameters showed a decrease in both groups, but this decrease was statistically significant in the group receiving combined anti-TNF treatment than the DMARD group. DAS28, VAS and HAQ values were statistically different between the two groups at the 6th month follow-up. ACR 20, 50 and 70 responses were 81, 54 and 22% in the group receiving anti-TNF drug combined with methotrexate; 44, 15 and 0% in the patients receiving DMARD (p<0.001). Anti-TNF drugs, when combined with methotrexate, were found to be more effective in reducing disease activity, improving functional disability, and ACR responses than DMARDs.

Keywords

Anti TNF Drugs DMARDs Rheumatoid Arthritis

References

  • 1. Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):3–18.
  • 2. Verstappen SM, Bijlsma JW, Verkleij H, Buskens E, Blaauw AA, ter Borg EJ. Overview of work disability in rheumatoid arthritis patients as observed in cross-sectional and longitudinal surveys. Arthritis Rheum. 2004;51(3):488-97.
  • 3. Alamanos IY, Voulgari PV, Drosos AA. Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis and Rheum. 2006;36(3):182-8.
  • 4. Karlson EW, Deane K. Environmental and gene-environment interactions and risk of rheumatoid arthritis. Rheum Dis Clin North Am. 2012;38(2):405–26.
  • 5. de Vries N, Tak PP, Tijssen H, van Riel PL, van de Putte LB. Female sex increases risk for rheumatoid arthritis only in individuals encoding low‐risk HLA‐DRB1 alleles. Arthritis Rheum. 2003;48:1762-3.
  • 6. Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol. 2014;35:347–69.
  • 7. Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat Rev Rheumatol. 2013;9(1):24-33.
  • 8. Wijbrandts CA, Dijkgraaf MG, Kraan MC, et al. The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor α expression in the synovium. Ann Rheumat Dis. 2008; 67:1139–44.
  • 9. Taylor PC, Feldmann M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat Rev Rheumatol. 2009;5(10):578-82.
  • 10. Todoerti M, Maglione W, Bernero E, et al. Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis. Reumatismo. 2013;65(5):207-18.
  • 11. Dalrymple JM, Stamp LK, O'Donnell JL, Chapman PT, Zhang M, Barclay ML. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:3299–308.
  • 12. Dale J, Alcorn N, Capell H, Madhok R. Combination therapy for rheumatoid arthritis: methotrexate and sulfasalazine together or with other DMARDs. Nat Clin Pract Rheumatol. 2007;3(8):450-8.
  • 13. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6:15.
  • 14. Bykerk VP, Massarotti EM. The new ACR/EULAR remission criteria: rationale for developing new criteria for remission. Rheumatology (Oxford). 2012;51(6):16-20.
  • 15. O'Dell JR, Mikuls TR, Taylor TH, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369(4):307-18.
  • 16. Moreland LW, O'Dell JR, Paulus HE, et al; TEAR Investigators. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012;64(9):2824-35.
  • 17. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315-24.
  • 18. Sokka T. Assessment of pain in rheumatic diseases. Clin Exp Rheumatol. 2005;23(39):77-84.
  • 19. Maska L, Anderson J, Michaud K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ‐II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL). Arthritis Care Res. 2011;63(11):4–13.
  • 20. Fleischmann R, van der Heijde D, Koenig AS, et al. How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index? Ann Rheum Dis. 2015;74(6):1132-7.
  • 21. Ranganath VK, Khanna D, Paulus HE. ACR remission criteria and response criteria. Clin Exp Rheumatol. 2006;24:14-21.
  • 22. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762–84.
  • 23. van Vollenhoven RF, Ernestam S, Geborek P, et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009;374(9688):459-66.
  • 24. Ma MH, Kingsley GH, Scott DL. A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2010;49(1):91-8.
  • 25. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964–75.
  • 26. Klareskog L, van der Heijde D, de Jager JP, et al. TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;28;363(9410):675-81.
  • 27. Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;2;372(9636):375-82.
  • 28. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54(1):26-37.
  • 29. Leirisalo-Repo M, Kautiainen H, Laasonen L, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann of the Rheum Dis. 2013;72(6):851-7.
  • 30. Smolen JS, Emery P, Fleischmann R, et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014;383(9914):321-32.
  • 31. Kırnap M, Demir H, Kalkan A. Comparison of the efficacy and side effects of cyclosporine-A and methotrexate in the treatment of the patients with rheumatoid arthritis. Erciyes Med J. 2000;22(4):178-84.
  • 32. Atzeni F, Gianturco L, Talotta R, et al. Investigating the potential side effects of anti-TNF therapy for rheumatoid arthritis: cause for concern? Immunotherapy. 2015;7(4):353-61.
  • 33. Strangfeld A, Hierse F, Kekow J, et al. Comparative effectiveness of TNF alpha inhibitors in combination with either methotrexate or leflunomide. Ann Rheum Dis. 2009; 68(12):1856-62.

Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması

Year 2020, Volume: 7 Issue: 1, 6 - 11, 28.04.2020

Türkan Turgay Ali Aydeniz Savaş Gürsoy

Abstract

Bu çalışmada romatoid artrit (RA) tedavisinde eklem hasarının önlenmesi veya kontrol altına alınması yoluyla DMARD (Disease Modifying Anti-Rheumatismal Drug) grubu ilaçlar ve metotreksat ile kombine anti TNF (Tümör Nekroz Faktör) ilaç tedavisinin hastalık aktivite kriterlerine göre etkinliğini kıyasladık. Çalışmamıza 24 hafta süre ile takip edilmiş verileri eksiksiz 75 aktif RA hastası alındı. Hastaların demografik özellikleri, DAS28 (Disease Activity Score), VAS (Visual Analogue Scale), HAQ (Health Assessment Questionnaire) parametreleri ve laboratuar değerlendirmeleri retrospektif olarak dosyalarından kaydedildi. Hastalar metotreksatla kombine anti TNF (infliksimab, etanersept, adalimumab) alan 37 hasta; DMARD (leflunomid+metotreksat, sulfasalasin+metotreksat, sadece metotreksat) alan 38 hasta olmak üzere 2 ayrı grupta incelendi. Tedavi etkinliği ACR (American College of Rheumatology) 20, 50 ve 70 kriterleriyle hesaplandı. Kombine anti TNF ilaç ile DMARD kullanan hastaların yaş ortalaması sırasıyla 50.27±7.9 ve 46.79±8.6 olarak hesaplanmıştır. Gruplar arasında tedavi öncesinde bakılan parametrelerden sadece HAQ arasında istatistiksel olarak anlamlı farklılık saptanmıştır. Gruplar arasında bakılan tedavi öncesi ve sonrası parametreler her iki grupta azalma göstermektedir ancak bu azalma kombine anti TNF tedavisi alan grupta DMARD grubundan istatistiksel olarak daha anlamlı bulunmuştur. Her iki grup arasında 6. ay kontrollerinde bakılan DAS28, VAS ve HAQ değerlerinde istatistiksel olarak anlamlı farklılık saptanmıştır. ACR 20, 50 ve 70 cevapları metotreksat ile kombine anti TNF ilaç alan grupta sırasıyla %81, 54 ve 22 iken; DMARD alan grupta %44, 15 ve 0 olarak saptanmıştır (p<0.001). Metotreksat ile kombine edildiğinde anti TNF ilaçların, DMARD’lara kıyasla hastalık aktivitesini azaltmada, fonksiyonel özürlülüğü iyileştirmede ve ACR yanıtlarında istatistiksel olarak daha etkin olduğu bulunmuştur.

Keywords

Anti TNF İlaçlar DMARD Romatoid Artrit

References

  • 1. Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):3–18.
  • 2. Verstappen SM, Bijlsma JW, Verkleij H, Buskens E, Blaauw AA, ter Borg EJ. Overview of work disability in rheumatoid arthritis patients as observed in cross-sectional and longitudinal surveys. Arthritis Rheum. 2004;51(3):488-97.
  • 3. Alamanos IY, Voulgari PV, Drosos AA. Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis and Rheum. 2006;36(3):182-8.
  • 4. Karlson EW, Deane K. Environmental and gene-environment interactions and risk of rheumatoid arthritis. Rheum Dis Clin North Am. 2012;38(2):405–26.
  • 5. de Vries N, Tak PP, Tijssen H, van Riel PL, van de Putte LB. Female sex increases risk for rheumatoid arthritis only in individuals encoding low‐risk HLA‐DRB1 alleles. Arthritis Rheum. 2003;48:1762-3.
  • 6. Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol. 2014;35:347–69.
  • 7. Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat Rev Rheumatol. 2013;9(1):24-33.
  • 8. Wijbrandts CA, Dijkgraaf MG, Kraan MC, et al. The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor α expression in the synovium. Ann Rheumat Dis. 2008; 67:1139–44.
  • 9. Taylor PC, Feldmann M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat Rev Rheumatol. 2009;5(10):578-82.
  • 10. Todoerti M, Maglione W, Bernero E, et al. Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis. Reumatismo. 2013;65(5):207-18.
  • 11. Dalrymple JM, Stamp LK, O'Donnell JL, Chapman PT, Zhang M, Barclay ML. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:3299–308.
  • 12. Dale J, Alcorn N, Capell H, Madhok R. Combination therapy for rheumatoid arthritis: methotrexate and sulfasalazine together or with other DMARDs. Nat Clin Pract Rheumatol. 2007;3(8):450-8.
  • 13. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6:15.
  • 14. Bykerk VP, Massarotti EM. The new ACR/EULAR remission criteria: rationale for developing new criteria for remission. Rheumatology (Oxford). 2012;51(6):16-20.
  • 15. O'Dell JR, Mikuls TR, Taylor TH, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369(4):307-18.
  • 16. Moreland LW, O'Dell JR, Paulus HE, et al; TEAR Investigators. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012;64(9):2824-35.
  • 17. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315-24.
  • 18. Sokka T. Assessment of pain in rheumatic diseases. Clin Exp Rheumatol. 2005;23(39):77-84.
  • 19. Maska L, Anderson J, Michaud K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ‐II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL). Arthritis Care Res. 2011;63(11):4–13.
  • 20. Fleischmann R, van der Heijde D, Koenig AS, et al. How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index? Ann Rheum Dis. 2015;74(6):1132-7.
  • 21. Ranganath VK, Khanna D, Paulus HE. ACR remission criteria and response criteria. Clin Exp Rheumatol. 2006;24:14-21.
  • 22. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762–84.
  • 23. van Vollenhoven RF, Ernestam S, Geborek P, et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009;374(9688):459-66.
  • 24. Ma MH, Kingsley GH, Scott DL. A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2010;49(1):91-8.
  • 25. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964–75.
  • 26. Klareskog L, van der Heijde D, de Jager JP, et al. TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;28;363(9410):675-81.
  • 27. Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;2;372(9636):375-82.
  • 28. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54(1):26-37.
  • 29. Leirisalo-Repo M, Kautiainen H, Laasonen L, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann of the Rheum Dis. 2013;72(6):851-7.
  • 30. Smolen JS, Emery P, Fleischmann R, et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014;383(9914):321-32.
  • 31. Kırnap M, Demir H, Kalkan A. Comparison of the efficacy and side effects of cyclosporine-A and methotrexate in the treatment of the patients with rheumatoid arthritis. Erciyes Med J. 2000;22(4):178-84.
  • 32. Atzeni F, Gianturco L, Talotta R, et al. Investigating the potential side effects of anti-TNF therapy for rheumatoid arthritis: cause for concern? Immunotherapy. 2015;7(4):353-61.
  • 33. Strangfeld A, Hierse F, Kekow J, et al. Comparative effectiveness of TNF alpha inhibitors in combination with either methotrexate or leflunomide. Ann Rheum Dis. 2009; 68(12):1856-62.
There are 33 citations in total.

Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section Original Article
Authors

Türkan Turgay 0000-0002-6348-3340

Ali Aydeniz 0000-0001-5701-3951

Savaş Gürsoy This is me 0000-0002-1673-9905

Publication Date April 28, 2020
Submission Date September 17, 2019
Published in Issue Year 2020 Volume: 7 Issue: 1

Cite

APA Turgay, T., Aydeniz, A., & Gürsoy, S. (2020). Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 7(1), 6-11.
AMA Turgay T, Aydeniz A, Gürsoy S. Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması. MMJ. April 2020;7(1):6-11.
Chicago Turgay, Türkan, Ali Aydeniz, and Savaş Gürsoy. “Romatoid Artritli Hastalarda Anti TNF Ve DMARD Tedavilerinin Hastalık Aktivite Ve İyileşme Kriterlerine Göre Karşılaştırılması”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 7, no. 1 (April 2020): 6-11.
EndNote Turgay T, Aydeniz A, Gürsoy S (April 1, 2020) Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 7 1 6–11.
IEEE T. Turgay, A. Aydeniz, and S. Gürsoy, “Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması”, MMJ, vol. 7, no. 1, pp. 6–11, 2020.
ISNAD Turgay, Türkan et al. “Romatoid Artritli Hastalarda Anti TNF Ve DMARD Tedavilerinin Hastalık Aktivite Ve İyileşme Kriterlerine Göre Karşılaştırılması”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 7/1 (April 2020), 6-11.
JAMA Turgay T, Aydeniz A, Gürsoy S. Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması. MMJ. 2020;7:6–11.
MLA Turgay, Türkan et al. “Romatoid Artritli Hastalarda Anti TNF Ve DMARD Tedavilerinin Hastalık Aktivite Ve İyileşme Kriterlerine Göre Karşılaştırılması”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, vol. 7, no. 1, 2020, pp. 6-11.
Vancouver Turgay T, Aydeniz A, Gürsoy S. Romatoid Artritli Hastalarda Anti TNF ve DMARD Tedavilerinin Hastalık Aktivite ve İyileşme Kriterlerine Göre Karşılaştırılması. MMJ. 2020;7(1):6-11.
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