Publication: Sıçan kavernozal sinir hasarı modelinde adipoz doku kaynaklı mezenkimal kök hücrelerin erektil işlevlerinin iyileştirilmesinde etkinliği
Abstract
GİRİŞ: Romatoid artrit (RA); etyolojisi belli olmayan, kronik olarak eklemleri tutan ve deformitelerle seyreden sistemik bir hastalıktır. RA’li olguların çoğunluğunda hastalık ortaya çıktıktan sonraki ilk iki yıl içerisinde sıklıkla belirgin eklem hasarı görülmektedir. Romatoid artrit tedavisinde kullanılan ilaçları hastalığın seyrini değiştirdiği kabul edilen (DMARD = Disease Modifying Anti Rheumatic Drugs) ve Rituximab Bu ilaçlar uygun şekilde kullanıldıklarında erozyonların ortaya çıkışını önlemekte veya yavaşlatmaktadırlar.Bu grup ilaçlarla yanıt alınamayan hastalarda ise biyolojik ajanlar olan Tümör nekrozis faktör-α blokerleri (infliksimab etanercept adalimumab) veya CD20 monokolonal antikoru Rituximab kullanılmaktadır. Bu güne kadar yapılan çalışmalarda tedaviye yanıt hastalığın seyrinin nasıl olacağını tahmin edebilmek için çeşitli markerlar üzerinde durulmuştur. Fakat serolojik markerların RA teavisindeki yeri henüz bilinmemektedir. METOD: Marmara Üniversitesi Tıp Fakültesi Hastanesi romatoloji polikliniğinde Ocak 2009- Ocak 2010 tarihleri arasında romatoid artrit tanısı almış 40 hasta çalışmaya alınmıştır. İlk grup 20 hastadan oluşuyordu. Bu hastalar en az 6 ay anti-TNF grup ilaçlardan bir veya ikisini kullanırken DAS 28 de 1.6 iyileşme sağlayıp bu tedaviye devam edenlerdi. Diğer 20 hasta ise en az 6 ay anti-TNF grup ilaçlardan bir veya ikisini kullanırken DAS28 de 1.6 iyileşme sağlanmamış olması nedeniyle rituximab tedavisine geçenlerden oluştu. Demografik özellikleri açısından anlamlı fark olmayan Her iki gruptada serumda RF serotiplerine bakıldı. SONUÇLAR: Tedavi öncesi ve sonrası DAS28 deki değişim (ortalama DAS28 skorundaki düşme olarak) grup2 ‘de anlamlı olarak daha fazla; Tedavi öncesi DAS28 vsTedavi sonrası DAS28 = 5.80±1.02 vs 19.85±1.27, p=0.17 Tedavi öncesi ve sonrası hastaların fonksiyonel sınıflarındaki değişim (ortalama düşme olarak) grup2 de anlamlı olarak daha fazla; tedavi öncesi fonksiyonel sınıf vs tedavi sonrası fonksiyonel sınıf = 0.15±0.36 vs 0.8±0.41, p<0.001 Rituximab ile tedaviye geçilen hastalarda RF pozitiflik oranı anlamlı olarak daha yüksek. anti-TNF grubunda(grup1) RF - / + vs Rituximab(grup2) grubunda = 13/ 7 vs. 0/ 20, p<0.001 grup 2 ile grup 1 karşılaştırıldığında IgRF değerlerinin tamamı ortalama olarak daha yüksek bulundu. IgARF (grup1 vs. Grup2) = 0.56±0.64 vs. 1.56±0.88,p<0.001 IgMRF (grup1 vs. Grup2 = 1.28±1.06 vs. 2.19±0.95,p<0.001 ve IgGRF (grup1vs. Grup2) = 0.16±0.12 vs. 0.46±0.58,p<0.001 Tedavi öncesi ve sonrası ESR deki değişim (ortalama ESR düşme olarak) grup2 de anlamlı olarak daha fazla; Tedavi öncesi ESR vs Tedavi sonrası ESR= 0.5513.01± vs 1.47±15.39, p=0.003 Tedavi öncesi ve sonrası CRP deki değişim (ortalama CRP vs düşme olarak) grup2 de anlamlı olarak daha fazla; Tedavi öncesi CRP vs Tedavi sonrası CRP= 3.75±7.71 vs 10.95±12.33, p=0.03 Rituximab ile tedaviye geçilen hastalarda ekstra-artiküler hastalık (EAH) bulunma sıklığı daha yüksek. anti-TNF grubunda EAH yok vs var / Rituximab grubunda = 19/ 1 vs. 9/ 11, p=0.001 Rituximab grubunda kemik erozyonu sıklığının (KE) anti- TNF grubunda kalan hastalara göre fazla olduğu gözlendi. (Anti-TNF grubunda KE yok/ var vs Rituximab grubu= 15/ 5 vs. 6/ 14, p=0.01 ) TARTIŞMA: Rituximab ile tedaviye geçilen hastalarda bakılan RF subgrupları anlamlı olarak daha yüksek bulunması tedavi yanıtını önceden belirlemede RF subgruplarına bakılması yol gösterici olabilir. Ayrıca ekstraartıküler hastalık bulunması IgA ve IgG RF düzeyleriyle ilişkili olabilir.
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease of unknown etiology. RA causes severe joint destruction in most of the patinets whithin the very first years of disease onset. Mainly DMARDs (Disease Modifying Anti Rheumatic Drugs) are used to treat RA. Proper use of these drugs result in prevention or at least in a delayed onset of destructive changes. In patients refractory to conventional treatment biologic agents against tumor necrosis factor alpha (Anti -TNF α), namely infliximab, etanercept and adalimumab, and rituximab are used. Up to date data on the interpretation of serological markers in relation to disease treatment is sparse. METHOD: Fourty patients diagnosed with RA at the outpatient clinics of the Marmara University department of rheumatology were included to the study between January, 2009 and January 2010. First set of 20 patients were treated with at least one biologic agent and had a response to treatment measured as a decrease in DAS 28 at least 1.6 points. The second set of patients were treated with at least one biologic agents for six months but were switched to rituximab because of lack of response to therapy and had a decrease less than 1.6 points in DAS28 disease activity score. Serum RF subtypes were analized in both groups. Demographic data did not differ in both groups. RESULTS: Change in DAS28 disease activity score after treatment was more emphasized in group 2 when compared (Mean DAS28 score before and after treatment; 19.85±1.27 vs. 5.80±1.02, p=0.17). Change in functional class (mean decrease) was also more prominent in group two (Functional class prior to- and after treatment : 0.8±0.41 vs. 0.15±0.36, p<0.001). Prevalance of RF was significantly higher in the rituximab treatment group (RF prevalence in anti-TNF vs. rituximab treatment groups: 13/ 7 vs. 0/ 20, p<0.001) In the rituximab treatment group mean RF values were higher in all subclasses; IgARF (Group 1 vs. Group 2) = 0.56±0.64 vs. 1.56±0.88,p<0.001 IgMRF (Group 1vs. Group 2 = 1.28±1.06 vs. 2.19±0.95,p<0.001 ve IgGRF (Group 1vs. Group 2) = 0.16±0.12 vs. 0.46±0.58,p<0.001 In the group 2, mean change in ESR was higher after treatment; ESR before vs. after treatment: 0.55±13.01 vs 1.47±15.39, p=0.003. Mean change in CRP levels was higher in the rituximab patient group, also; CRP levels before vs. after treatment: 3.75±7.71 vs 10.95±12.33, p=0.03. The prevalance of extraarticular disease was higher in the rituximab patient group; Extraarticular disease prevalance in the anti TNF treatment group vs. rituximab treatment group; 1/ 20 vs. 11/ 20, p=0.001 DISCUSSION: Mean serum levels of all RF subgroups, especially IgA and IgG RF levels were higher in the rituximab treatment group. Together with the presence of extraarticular disease, these parameters are suggested to be associated with the response to therapy.
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease of unknown etiology. RA causes severe joint destruction in most of the patinets whithin the very first years of disease onset. Mainly DMARDs (Disease Modifying Anti Rheumatic Drugs) are used to treat RA. Proper use of these drugs result in prevention or at least in a delayed onset of destructive changes. In patients refractory to conventional treatment biologic agents against tumor necrosis factor alpha (Anti -TNF α), namely infliximab, etanercept and adalimumab, and rituximab are used. Up to date data on the interpretation of serological markers in relation to disease treatment is sparse. METHOD: Fourty patients diagnosed with RA at the outpatient clinics of the Marmara University department of rheumatology were included to the study between January, 2009 and January 2010. First set of 20 patients were treated with at least one biologic agent and had a response to treatment measured as a decrease in DAS 28 at least 1.6 points. The second set of patients were treated with at least one biologic agents for six months but were switched to rituximab because of lack of response to therapy and had a decrease less than 1.6 points in DAS28 disease activity score. Serum RF subtypes were analized in both groups. Demographic data did not differ in both groups. RESULTS: Change in DAS28 disease activity score after treatment was more emphasized in group 2 when compared (Mean DAS28 score before and after treatment; 19.85±1.27 vs. 5.80±1.02, p=0.17). Change in functional class (mean decrease) was also more prominent in group two (Functional class prior to- and after treatment : 0.8±0.41 vs. 0.15±0.36, p<0.001). Prevalance of RF was significantly higher in the rituximab treatment group (RF prevalence in anti-TNF vs. rituximab treatment groups: 13/ 7 vs. 0/ 20, p<0.001) In the rituximab treatment group mean RF values were higher in all subclasses; IgARF (Group 1 vs. Group 2) = 0.56±0.64 vs. 1.56±0.88,p<0.001 IgMRF (Group 1vs. Group 2 = 1.28±1.06 vs. 2.19±0.95,p<0.001 ve IgGRF (Group 1vs. Group 2) = 0.16±0.12 vs. 0.46±0.58,p<0.001 In the group 2, mean change in ESR was higher after treatment; ESR before vs. after treatment: 0.55±13.01 vs 1.47±15.39, p=0.003. Mean change in CRP levels was higher in the rituximab patient group, also; CRP levels before vs. after treatment: 3.75±7.71 vs 10.95±12.33, p=0.03. The prevalance of extraarticular disease was higher in the rituximab patient group; Extraarticular disease prevalance in the anti TNF treatment group vs. rituximab treatment group; 1/ 20 vs. 11/ 20, p=0.001 DISCUSSION: Mean serum levels of all RF subgroups, especially IgA and IgG RF levels were higher in the rituximab treatment group. Together with the presence of extraarticular disease, these parameters are suggested to be associated with the response to therapy.