Tesis

Hubungan Kadar Interleukin-6 (IL-6) dan Tumor Necrosis Factor-a (TNF-a) dengan Methotrexate-Polyglutamate 3 (MTX-PG3) pada Pasien Artritis Reumatoid = Relationship of Interleukin-6 (IL-6) and Tumor Necrosis Factor-a (TNF-a) Levels with Methotrexate-Polyglutamate 3 (MTX-PG3) in Rheumatoid Arthritis Patient.

Latar Belakang : Artritis Reumatoid (AR) merupakan salah satu penyakit autoimun yang ditandai oleh inflamasi sistemik kronik dan progresif, dimana sendi merupakan target utama. Metotreksat (MTX) telah digunakan sebagai pengobatan utama pasien AR karena memberikan hasil yang lebih baik dibandingkan dengan Disease Modifying Arthritis Rheumatoid Drugs (DMARD) lain. Kadar MTX-PG terutama MTX-PG3 dalam darah diperkirakan berpengaruh terhadap sitokin pro-inflamasi pada AR. Namun saat ini, belum didapatkan penelitian yang menilai korelasi antara kadar MTX-PG3 dengan kadar Interleukin-6 (IL-6) dan Tumor Necrosis Factor-a (TNF-a) pada AR setelah terapi MTX selama 16 minggu. Tujuan : Penelitian bertujuan untuk mendapatkan gambaran efikasi terapi MTX terhadap sitokin pro-inflamasi melalui pemeriksaan MTX-PG3 pada pasien AR. Metode : Penelitian ini merupakan studi analitik observasional dengan jenis rancangan prospective cohort study. Hasil : Penelitian ini dilakukan pada 30 pasien AR. Pada minggu ke-0 didapatkan rerata C-Reactive Protein (CRP) sebesar 5,2 mg/L, aktivitas penyakit berdasarkan CRP (DAS28-CRP) sebesar 4,08 (sedang), kadar IL-6 sebesar 5,16 pg/ml dan kadar TNF-a sebesar 9,81 pg/ml. Pada minggu ke-16 didapatkan rerata CRP sebesar 3,05 mg/L, DAS28-CRP sebesar 2,62 (ringan), kadar IL-6 sebesar 2,74 pg/ml, kadar TNF-a sebesar 7,82 pg/ml dan MTX-PG3 sebesar 8,61 nmol/L. Rerata perubahan DAS28CRP (ΔDAS28-CRP) sebesar 1,46. Pada penelitian ini tidak didapatkan beda rerata kadar IL-6 (p=0,443) dan TNF-a (p=0,057) minggu ke-0 dan minggu ke-16.Tidak didapatkan korelasi MTX-PG3 dengan kadar IL-6 (r=0250, p=0,184), TNF-a (r=-0,146, p=0,441) dan ΔDAS28-CRP (r=-0,063, p=0,741) pada minggu ke-16. Dosis MTX, usia dan Laju Filtrasi Glomerolus (LFG) mempengaruhi kadar MTX-PG3 (p < 0,25). Simpulan : Tidak didapatkan korelasi antara kadar IL-6 dan TNF-a dengan MTX-PG3 pada minggu ke-16, serta dosis MTX, usia dan LFG mempengaruhi MTX-PG3 pada AR.
Kata kunci: Artritis reumatoid, MTX-PG3, IL-6, TNF-a, DAS28-CRP


Backgroud : Rheumatoid arthritis (AR) is an autoimmune disease characterized by chronic and progressive systemic inflammation, in which joints are the main target. Methotrexate (MTX) has been used as the main treatment for AR patients because it gives better results compared to other Disease Modifying Arthritis Rheumatoid Drugs (DMARD). MTX-PG levels, especially MTX-PG3 in the blood are thought to have an effect on pro-inflammatory cytokines in AR. However, currently there are no studies that have assessed the correlation between Interleukin-6 (IL-6) and Tumor Necrosis Factor-a (TNF-a) levels and MTX-PG3 in AR patient after 16 th weeks of MTX therapy. Objective : The aim of this study was to describe the efficacy of MTX therapy against pro-inflammatory cytokines through the examination of MTX-PG3 in AR patients. Methods : This research is an observational analytic study with a prospective cohort study design. Results : This study was conducted on 30 AR patients. At 0-week the mean C-Reactive Protein (CRP) levels was 5.2 mg/L, disease activity based on CRP (DAS28-CRP) was 4.08 (moderate), IL-6 levels was 5.16 pg/ml. and TNF-a levels was 9.81 pg/ml. At 16 th week, the mean CRP levels was 3.05 mg/L, DAS28-CRP was 2.62 (mild), IL-6 levels were 2.74 pg/ml, TNF-a levels were 7.82 pg/ml and MTX-PG3 levels was 8.61 nmol/L. The mean change in DAS28-CRP (ΔDAS28-CRP) was 1.46. In this study, there was no mean difference levels of IL-6 (p=0.443) and TNF-a (p=0.057) at 0-week and 16 th weeks. There was no correlation between MTX-PG3 and levels of IL-6 (r=0250, p=0.184), TNF-a (r=-0.146, p=0.441) and ΔDAS28-CRP (r=-0.063, p=0.741) at 16 th week. MTX doses, age and Glomerular Filtration Rate (eGFR) affected MTX-PG3 levels (p < 0.25). Conclusion : There was no correlation between IL-6 and TNF-a levels with MTX-PG3 at 16 th weeks, MTX doses, age and eGFR affected MTX-PG3 in AR patient.
Keywords : Rheumatoid arthritis, MTX-PG3, IL-6, TNF-a, DAS28-CRP