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1 대한류마티스학회지 Vol. 15, No. 3, September, 2008 원저 한국인에서류마티스관절염의치료적관해 홍익병원류마티스내과 1, 이화여자대학교의학전문대학원류마티스내과 2, 삼성서울병원진단검사의학과 3 이유현 1 ㆍ이지수 2 ㆍ강은숙 3 =Abstract= Defining Remission of Korean Patients with Rheumatoid Arthritis You-Hyun Lee 1, Jisoo Lee 2, Eun-Sook Kang 3 Department of Rheumatology, Hongik Hospital 1, Department of Rheumatology, Ewha Womans University Mokdong Hospital 2, Department of Laboratory Medicine, Samsung Medical Center 3, Seoul, Korea Objective: To define the state of remission based on American College of Rheumatology (ACR) preliminary criteria in Korean patients with rheumatoid arthritis (RA). Methods: A hundred three patients of RA, followed up over 1 year, were selected at Ewha medical center from May 2000 to May Remission was defined by ACR preliminary criteria. Data were obtained from the initial and the last visit. Data on initial tender joint count (TJC) and swollen joint count (SJC), treatment, disease duration, remission duration were collected. Initial ESR, CRP, rheumatoid factor (RF), TJC and SJC were also performed at the last clinical visit or at the time of remission. Results: Patients in remission were 35%. The maintenance duration of remission was 4.8±9.0 (mean±sd) months. Remission group had shorter disease duration (20.2±34.7 vs. 58.2±83.2 months, p=0.010), were at earlier stage of the disease (<2 years of symptom onset) (80.6 vs. 52.2%, p=0.006) compared to non-remission group. Percentage of patients showing decrease in RF titer was significantly higher in the remission group compared to the non-remission group (p=0.049). However, seronegative conversion of RF was not related to remission status (15.6 vs. 14.8%). In the non-remission group, pain was the most persistently non-satisfying clinical variable of the ACR preliminary criteria. Conclusion: Patients at early stage of disease achieved clinical remission in higher rate. Changes of RF titer was affected by clinical remission status. <접수일 :2008년 4월 28일, 심사통과일 :2008년 6월 16일> 통신저자 : 이지수서울시양천구목 6동 이화여자대학교목동병원류마티스내과 Tel:02) , Fax:02) , leejisoo@ewha.ac.kr 204

2 이유현외 : Defining Remission of Korean RA Key Words: Rheumatoid arthritis, Remission, Criteria 서론류마티스관절염 (RA) 은다발성관절염을주증상으로하는전신질환으로진행이되면관절파괴와그에따른관절기능손실을초래한다. RA 환자를치료하는것은질병의염증활성도를조절하여관절손상의진행을막고, 궁극적으로는질병관해 (remission) 의상태를이루는데있다. 관해상태를판단하기위한여러항목들이환자치료반응평가에이용되었고이를통합한일관화된평가기준의필요성이대두되어, 1981년미국류마티스학회 (American College of Rheumatology:ACR) 는 RA 환자의치료중질병관해여부를판단하는 ACR 관해기준을제시하였다 (1). 이기준은 15분이내의조조강직, 피로감없음, 관절통없음, 관절압통없음, 관절부종없음과정상적혈구침강속도 (ESR) 수치 ( 남자<20 mm/hr, 여자 <30 mm/hr) 의 6가지항목중 5가지이상이최소한 2개월이상만족하는경우를관해로정의했다. 그러나당시 RA치료제의개발이아직미흡한단계로 RA의완치는어려운것으로인식되었고, 대부분의임상연구들이질병관해상태보다는염증의활성도를측정하는데중점을두어왔기때문에 ACR 관해기준은실제임상에서는널리이용되지않았다. 관해를질병활성도가낮은상태로보는관점때문에 ACR의관해기준보다는 Disease Activity Score (DAS) (2), ACR 질병활성도기준 (3) 등의질병활성도평가기준이치료후관해의도달을측정하는데적용되었다. 한편적절한평가기준을만들기위한노력이진행되었으며 ACR 관해기준에서일부항목이제외된기준이질병평가에적용되기도하였다. 이렇게관해기준을정의하고자하는시도가있었으나통합된결과는아직없으며 RA 관해와관련된요인도제대로정립되어있지않다. 이렇게 ACR 관해기준의실제적인임상적용은잘되지않고있는실정이다. 최근생물학적제제및새로운치료제의개발로 RA 질병활성도의조절이향상되었으며관해를이루기어려웠던 RA에서기대치를높일수있게되었 다 (4,5). 항류마티스약제 (Disease modifying anti- rheumatic drugs; DMARDs) 치료후 RA의관해를 ACR 관해기준으로설명한외국의연구자료들에서는 7 37% 의관해율을보여주었다 (6-8). DMARDs를통해 RA의질병활성도만을줄이는것이아니라관해를이룰수있는빈도가높아짐으로인해임상에서관해기준을치료에적용하여치료목표로삼을수있게되었다. 그러나한국인에서는 RA 관해가어느정도이루어지는지는아직연구된바가미흡하며, 이에본연구는 ACR 관해기준에근거하여한국인 RA 환자에서약물유도질병관해의정도를보고자하였다. 대상및방법 1. 대상환자및측정항목 2000년 5월에서 2006년 5월까지 6년의연구기간동안이화여자대학교부속목동병원류마티스내과외래에내원한환자중, 1987년 ACR 진단기준에따라 RA로진단받은환자를대상으로하였다. 이들중최소한 1년이상경과관찰이가능한환자중 103명을무작위로선택하여투여받은 DMARDs의수, RA의유병기간, 경과관찰한기간을조사하였다. 종양괴사인자 (TNF) 길항제를투여한환자는포함되지않았다. 이학적검사로동통이있는관절수 (tender joint count; TJC), 종창이있는관절수 (swelling joint count; SJC) 를검사하였고혈액검사는 ESR, C 반응성단백 (CRP), 류마티스인자 (RF) 를처음방문할때와마지막방문했을때측정하였다. 치료경과관찰중 ACR 관해기준에만족할경우관해로판단하여동일한이학적검사와혈액검사를측정하였고관해까지의기간, 관해유지기간을조사하였다. ESR은 Test-1 (Alifax, Italy) 을사용하여측정하였으며, CRP 와 RF는 Behring Nephelometer II (BN II, Dade Behring GmbH, Marburg, Germany) 를사용하여분석하였다. 2. 관해의평가연구시작시점과이후경과관찰중각각질병상태를 ACR 관해기준에근거하여평가하였다 ( 표 1). 205

3 대한류마티스학회지제 15 권제 3 호 2008 Table 1. American College of Rheumatology preliminary criteria for remission (1) Five or more of the following criteria must be fulfilled for a least 2 consecutive months 1. Duration of morning stiffness not exceeding 15 minutes 2. No fatigue 3. No joint pain by anamnesis 4. No joint tenderness or pain on motion 5. No soft tissue swelling in joints or tendon sheath 6. ESR<30 mm/hr for a female or 20 mm/hr for a male Table 2. Clinical and demographic characteristics of RA patients Variable n=103 Table 3. Remission status of RA patients Variable Remission, n (%) No remission, n (%) Mean duration until remission, mean±sd, months <12 months, n (%) months, n (%) >24 months, n (%) Mean maintenance duration of remission, mean±sd, months <12 months, n (%) >12 months, n (%) 36 (35) 67 (65) 15.6± (36.1) 16 (44.4) 7 (19.4) 13.8± (58.3) 15 (41.7) Female, % Mean age, years Mean age at onset of RA, years Mean disease duration, months with early arthritis (<2 years), % Mean follow-up duration, months Rheumatoid factor positive, % ± ± ± ± 평가항목은조조강직의지속시간이 15분이내, 피로감없음, 관절통없음, 관절압통없음, 관절이나건막의조직부종없음, ESR의감소 ( 여성인경우 30 mm/hr 미만, 남성인경우 20 mm/hr 미만 ) 로이중 5항목이상이최소한 2개월이상연속하여지속되는경우를관해로보았다. 3. 통계적방법측정결과는평균 ± 표준편차 (SD) 로표시하였고통계처리는 SPSS 12.0 (SPSS, Chicago, IL) 을사용하여분석하였다. 관해군과비관해군간의비교는 χ 2 - test와 student t-test를사용하였고 p값은 0.05미만을통계적으로유의하다고판정하였다. 결과 1. 환자의임상적특성환자는총 103명으로평균나이는 54.7±14.9세였고, 여성이 86명 (83.5%) 으로많았다. RA 증상이시작된평균나이는 50.9±14.9세이었고평균유병기간 Fig. 1. Distribution of remission duration in remission group is shown by Kaplan-Meier analysis. Patients on remission within 12 months are 36.1% (13/36). 은 44.9±72.3개월, 평균경과관찰기간은 41.7± 16.4 개월이었다. 이들중관절염이 2년이내에발생하여치료했던초기의 RA 환자는 62.1% 였으며 RF 양성인환자의비율은 83.5% 였다 ( 표 2). 2. 질병관해의양상 연구기간동안질병관해에도달한환자는 36명으로 35% 를차지하였고관해에도달하지못한환자는 67명 (65%) 이었다. 관해에도달하기까지평균기간은 15.6±7.9개월이었고, 관해유지평균기간은 13.8± 10.5 개월이었으며 ( 표 3) 관찰 1년째 13명 (36.1%) 에서관해를이루었고 2년째 16명 (44.4%), 3년째 7명 (19.4%) 이관해를이루었다 ( 그림 1). 이중, 12개월이상관해를유지한환자는 41.7% 이었다 ( 표 3). 206

4 이유현외 : Defining Remission of Korean RA Table 4. Comparison of clinical and demographic characteristics of RA patients according to the state of remission Remission (n=36) No remission (n=67) p Female, % Mean age, years Mean disease duration, months With early arthritis (<2years), % Follow up duration, months Rheumatoid factor positive, % Initial titer of rheumatoid factor, IU/mL Mean number of initial tender joint Mean number of initial swollen joint Initial ESR, mm/hr Initial CRP, mg/dl Mean number of DMARDs used, no. (range) Methotrexate, % DMARDs combination therapy, % ± ± ± ± ± ± ± (1 4) ± ± ± ± ± ± ± (1 5) Table 5. Comparison of rheumatoid factor changes during the follow up period in seropositive RA patients between the remission group and the nonremission group Rheumatoid factor decrease Rheumatoid factor increase Seronegative conversion* Remission n=32 (%) 27 (84.4) 5 (15.6) 5 (15.6) No remission n=54 (%) 34 (63) 20 (37) 8 (14.8) p *decrease in rheumatoid factor titer to negative value 3. 관해군과비관해군의특성비교관해를영향을주는인자를분석하기위해환자를관해군과비관해군으로나누어임상적특성을비교하였다. 두군사이에나이나성별의차이는없었다. 관해군의경우평균질병이환기간이비관해군보다짧은양상을나타내었고 (20.2±34.7개월 vs. 58.2±83.2 개월, p=0.010), 2년이내의관절염유병기간을가진경우는관해군에서 80.6% 로더많았다 (p=0.006). 초기 TJC와 SJC, RF, ESR, CRP는의미있는차이를보이지않았다. 치료약제로사용한 DMARDs의수는관해군 2.2개, 비관해군 2.5개로차이가없었으며 Fig. 2. Changes in rheumatoid factor titer during the follow up period in RA remission group (A), non-remission group (B). 207

5 대한류마티스학회지제 15 권제 3 호 2008 Table 6. Distribution of ACR remission criteria in RA patients who did not achieved remission at follow up Morning stiffness <15 min* No fatigue* No joint pain* No tender joint* No swollen joint* Normal ESR *p<0.05 Criteria satisfying, n (%) 33 (49.3) 43 (64.2) 1 (1.5) 33 (49.3) 28 (41.8) 53 (79.1) Criteria non-satisfying, n (%) 34 (50.7) 24 (35.8) 66 (98.5) 34 (50.7) 39 (58.2) 14 (20.9) 메토트렉세이트 (MTX) 등의각약제별사용여부는양군간에차이가없었고치료제의병합요법의여부는관해에의미있는영향력을보여주지는않았다 ( 표 4). RF 양성인환자에서초기와추적관찰시 RF 의역가의감소를보이는환자는관해군에서빈도가더높았고, 반면에 RF 역가의증가를보이는환자는비관해군에서빈도가더높았다 ( 각각 p=0.049) ( 표 5). RF 양성과음성인모든환자를포함하여관해군과비관해군을비교하였을때치료후에양군모두에서 RF 역가가의미있게감소하는경향을보였다 (p=0.000 vs. p=0.008) ( 그림 2). RF의음성변환은관해군에서 15.6%, 비관해군에서 14.8% 로두군간에차이를보이지않았다 ( 표 5). 4. ACR 관해기준의항목별중요도 비관해군에서나타나는임상양상을 ACR 관해기준에근거하여검토해보았을때관절통은비관해군 66명 (98.5%) 에서남아있어관해기준을만족시키지가장중요한요인이었고, ESR은비관해상태임에도 79.1% 서정상수치를보여관해의여부를판정하는항목으로는변별력이떨어짐을알수있었다 ( 표 6). 고 질병관해의개념은여러질병, 특히종양분야에서발전되어왔다. 완치의개념과는차이가있을수있으며이전보고된연구들에서관해를이룰경우약제를완전히끊은상태에서관해가유지되는것이 찰 아니라약제를유지하면서일정상태를유지하는것으로완전치유의의미와는다르다고할수있다. RA에서항류마티스제제의발전이있기 50여년전에는관해율이 10% 정도였으나최근약물의발전으로관해율은높아지고있다 (9). 최근 DMARDs를비롯한적극적인치료와 DMARDs의복합요법, 생물학적제제의발달로치료성적이호전된만큼미국류마티스학회에서제시한질병호전 (ACR50 혹은 ACR70) 을얻어내기는용이해졌으나이는관해상태를반영하는것은아니며현재의추세는관해상태의정의를내리는데있어최소한의질병활성상태를이루는것을중요시하는경향이다. RA의관해는미국식품의약국 (FDA), 미국류마티스학회, 유럽류마티스학회 (EULAR) 의기준에의해정의한다 (10-12). 각각은측정항목에차이가있으며 EULAR의 DAS28은점수로질병활성도를보는것으로 2.6미만이 ACR 관해기준을만족한다고는하나 (13), FDA와 EULAR에서제시한기준으로는단시간내에환자의상태평가가쉽지않은단점이있다 (14). 이에비하여 ACR 관해기준은 6가지대표적인항목을기준으로하여상대적인증상의변화정도에중점을두었기때문에시간이적게소요되고임상적적용에는용이한면이있다. 1981년 Pinal 등이처음으로 ACR 관해기준을제시할당시는아직관해를이룰치료의발전이이루어지지않은상태였으며그이후로이를근거로한연구가진행되었으나임상적유용성에관한뚜렷한결과를제시해주지는못하였다 (6,15). 그러나 1985년 Wolfe 등이시행한전향적연구에서는 ACR 관해기준의민감도는 80.2%, 특이도는 96.2% 를나타내어임상적용에대한가능성을높여주었다 (6). RA의관해기준이적절한지여부에관한연구가지속되었고 1996년 Prevoo 등은피로감없음 (no fatigue) 의항목을없애고관절통은 VAS (visual analog scale) 로표시하자고제안한변형된진단기준을제시하였는데이는정립된것은아니나몇몇연구에서적용되었다 (16-18). 피로감은심부전과같은관절외장기의기능장애와관련되어나타날수있으며측정기준이모호하고, 관절통또한구조적으로이미심하게손상된경우와도연관되어있을수있기때문에제외의기준이될수있겠으나피로감이나조조강직 (morning 208

6 이유현외 : Defining Remission of Korean RA stiffness) 의항목은수면장애, 우울증뿐아니라방사선학적악화와운동장애 (physical disability), 사망률과같은장기적예후와관련되어있는것으로알려져있으므로 (3,19,20), OMERACT 7에서는 RA의기준에포함시켜야함을제안하였다 (21). ACR 관해기준을적용한본연구에서관해율은 35% 였는데이는 ACR 관해기준에근거하였을때관해율이최대 30% 내외에머물렀던외국의연구와비슷한결과를보였다 (6,8,15). 기존의보고된연구에서투여된 DMARDs가 gold나 penicillamine와같은약제이거나지역별로투여약제선택에차이가있어정확한비교가될수없으나한국인에서 DMARDs 의치료효과가인종에따른차이는보이지않는것으로추정해볼수있다. DMARDs는 RA의증상완화, 기능향상뿐아니라방사선학적악화를늦추는효과를보이나질병관해에대해서는아직충분한효과를보이지못했다. DMARDs 단일요법으로치료한경우 ACR 관해기준에따라관해를보인경우는 7 22% 였으며관해유지기간도짧았다 (7,17). 그러나 DMARDs 복합요법을투여한경우는장기간지속된 RA의경우관해율은 10% 이내였고 (16,22), 증상이시작된지 2년이내의초기 RA인경우 2년이내관해율이 0% 에서 10년이내 18% 까지다양하게보고되었다 (23-25). 2년여에걸친 FIN-RACo trial 에서피로감을제외한나머지진단기준을적용하여초기 RA환자에게복합치료를하였을때관해율이 37% 로단일치료를한경우 18% 보다높았음을보여주었다 (8). 이와같이 RA 환자에게조기에치료를시작하며, DMARDs 병합요법과같은적극적인치료를적용할때치료결과가좋음을제시하고있으나본연구에서는관해군과비관해군간에평균 2 가지이상의 DMARDs를복합치료한환자의비율은거의차이가없었다. 또한복합치료는관해까지이르는기간및관해유지기간에영향을주지않았다 ( 통계자료는보여주지않았음 ). 관해가일어나기쉬운인자는유병기간이짧은경우, 특히발병 2년이내의초기 RA인경우로관찰되어 RA의조기진단, 조기치료의중요성을확인하였다. 다양한새로운치료법으로관해를높일수있었던연구들이초기 RA를대상으로하였던이유도이와연관되어있다고하겠다. RF는 RA의방사선학적관절손상이나관절외증상, 또는질병의예후와연관이있는표지자로알려져있다 (26-28). RF와 RA의활성도의관련성은관절의압통, 종창등의임상증상과 ESR과같은염증표지자에비하면그중요도가적다. 그러나질병의활성도와 RF 수치의증감은연관되어있음을보고하고있고 (27), 본연구에서 DMARDs 치료후두군모두에서 RF 역가가의미있게감소하는경향을보였다. 이는 MTX 치료후에 RF의감소를보고한 Alarcon 등의연구와비슷한결과라고할수있다 (29). 초기 RF 수치는관해군과비관해군사이에의미있는차이를보이지않아관해여부, 즉 DMARDs에대한치료반응예측에치료전 RF가도움이되지는않을것으로보이나 DMARDs 치료후 RF 역가가감소하면관해를이룰수있는가능성이높아짐을예측할수있다. 관해기준항목은객관적인지표가대부분이며환자의주관적증상이포함된항목은쉽게변할수있으며기준이명확하지않을수있다. Balsa 등은 RA 환자 788명을대상으로 ACR 관해기준의각항목에대해서양성예측율을조사하였는데 1) 관절통없음, 2) 관절부종없음, 3) 관절압통없음, 4) 피로감없음, 5) 조조강직 15분이내, 6) 정상 ESR의순으로나타나관절통이없는경우가관해와가장관련있다고하였다 (16). 관절부종이가장호전되기힘들었던항목임을보고된적도있으나 (22), 본연구에서는비관해군에서관절통이남아있는경우가관해의기준을만족하지못한원인이었다. 그러나관해군에서도관절통이남아있는경우가 52.8% 로 ( 자료는제시하지않았음 ), 관절통은관해여부를구분하는지표로보기에중요도가적었다. ACR 관해기준에따라관해를판정받은환자에서관절통이 % 까지많이남아있는결과를보고한연구에서통증의정도를점수화하여비교하였는데관해가온경우가통증의강도가더낮은결과를보였다 (15). 본연구에서도관해군은 52.8%, 비관해군은 98.5% 의상당수환자에서관절통이남아있는양상을보였으나통증은주관적인지표이고, 통증의강도에도차이가있었을것으로사료된다. ESR은비관해군에서도 79.1% 로상당수에서정상치를보여정상 ESR 이외나머지 5가지의임상기준이관해 209

7 대한류마티스학회지제 15 권제 3 호 2008 기준판단에더욱중요함을보여주었다. ACR 관해기준이 6가지항목중에서 5가지이상만족하면관해상태로정의하므로, 환자가다른증상은호전되었으나관절통이여전히남아있는경우에도관해의상태로정의할수있다. 이렇게환자본인이느끼는관해의정도와는차이점이있을수있지만 RA의만성경과를고려할때 ACR 관해기준은단시간내에환자의평가가용이하고본연구에서와같이임상적인치료효과의판정에유용하다고하겠다. 증상과 ESR 결과가관해가온경우에방사선학적소견및기능적상태도호전되었는지의여부는확실치않으며, 대부분다른질병의관해기준들과마찬가지로경과관찰중한시점에서관해기준을만족한경우에도이후에지속적인관해상태를유지하는지의여부를예측할수는없다. 그러나치료를통한관해가 1차적목적이며, 관해를이룬경우환자의삶의질을높이기위한치료적접근이더욱용이하고나아가서치료의순응도도높일수있을것으로기대한다. 결 RA 환자의질병활성도가심화되기전에초기에적극적으로치료할경우, 더높은비율의임상적관해를얻을수있으며, 관해가되는경우 RF의역가또한감소하는경향을보였다. 일개병원에서의 RA 환자들을대상으로하였으나한국인 RA 환자의치료에서 ACR 관해기준은비교적간단하며유용한평가수단으로임상에서의적용을권고해볼수있겠다. 론 참고문헌 1) Pinals RS, Masi AT, Larsen RA. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 1981;24: ) Fuchs HA. The use of the disease activity score in the analysis of clinical trials in rheumatoid arthritis. J Rheumatol 1993;20: ) Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum 1993;36: ) Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, et al. 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;363: ) St. Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50: ) Wolfe F, Hawley DJ. Remission in rheumatoid arthritis. J Rheumatol 1985;12: ) Ferraccioli GF, Gremese E, Tomietto P, Favret G, Damato R, Di Poi E, et al. Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporine A, sulphasalazine) or monotherapy for three years. Rheumatology (Oxford) 2002; 41: ) Mӧttӧnen T, Hannonen P, Leirisalo-Repo M, Nissilӓ M, Kautiainen H, Korpela M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomized trial. FIN-RACo trial group. Lancet 1999;353: ) Short CL, Bauer W, Reynold WE. Rheumatoid arthritis. p , Cambridge, Havard University Press, ) Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38: ) van Gestel AM, Prevoo ML, van't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL, et al. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum 1996;39: ) Food and Drug Administration. Guidance for industry. Clinical development programs for drugs, devices, and biological products for the treatment of rheumatoid arthritis. US Department of Health and Human Services, FDA, February

8 이유현외 : Defining Remission of Korean RA 13) Fransen J, Creemers MCW, van Riel PLCM. Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology (Oxford) 2004;43: ) Sesin CA, Bingham CO, III. Remission in rheumatoid arthritis: wishful thinking or clinical reality? Semin Arthritis Rheum 2005;35: ) Alarcon GS, Blackburn Jr WD, Calvo A, Castaneda O. Evaluation of the American Rheumatism Association preliminary criteria for remission in rheumatoid arthritis: a prospective study. J Rheumatol 1987;14: ) Balsa A, Carmona L, Gonzalez-Alvaro I, Belmonte MA, Tena X, Sanmarti R, et al. Value of Disease Activity Score 28 (DAS28) and DAS28-3 compared to American College of Rheumatology-defined remission in rheumatoid arthritis. J Rheumatol 2004;31: ) Korpela M, Laasonen L, Hannonen P, Kautiainen H, Leirisalo-Repo M, Hakala M, et al. Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study. Arthritis Rheum 2004;50: ) Mottonen T, Hannonen P, Korpela M, Nissila M, Kautiainen H, Ilonen J, et al. Delay to institution fo therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum 2002;46: ) Belza BL. Comparison of self-reported fatigue in rheumatoid arthritis and controls. J Rheumatol 1995; 22: ) Belza BL, Henke CJ, Yelin EH, Epstein WV, Gillis CL. Correlates of fatigue in older adults with rheumatoid arthritis. Nurs Res 1993;42: ) Kirwan JR, Hewlett SE, Heiberg T, Hughes RA, Carr M, Hehir M, et al. Incorporating the patient perspective into outcome assessment in rheumatoid arthritis-progress at OMERACT 7. J Rheumatol 2005; 32: ) Prevoo ML, van Gestel AM, van't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL, et al. Remission in a prospective study of patients with rheumatoid arthritis: American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol 1996;35: ) Sokka T, Pincus T. Most patients receiving routine care for rheumatoid arthritis in 2001 did not meet inclusion criteria for most recent clinical trials or American College of Rheumatology criteria for remission. J Rheumatol 2003;30: ) Young A, Dixey J, Cox N, Davies P, Davlin J, Emery P, et al. How does functional disability in early rheumatoid arthritis (RA) affect patients and their live? Results of 5 years of follow-up in 732 patients from the Early RA study (ERAS). Rheumatology (Oxford) 2000;39: ) Lindqvist E, Saxne T, Geborek P, Eberhardt K. Ten year outcome in a cohort of patients with early rheumatoid arthritis: health status, disease process, and damage. Ann Rheum Dis 2002;61: ) Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ, et al. Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis Rheum 2002;46: ) van Zeben D, Hazes JM, Zwinderman AH, Cats A, van der Voort EA, Breedveld FC, et al. Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. Ann Rheum Dis 1992;51: ) van Schaardenburg D, Hazes JM, de Boer A, Zwinderman AH, Meijers KA, Breedveld FC. Outcome of rheumatoid arthritis in relation to age and rheumatoid factor at diagnosis. J Rheumatol 1993;20: ) Alarcon GS, Schrohenloher RE, Bartolucci AA, Ward JR, Williams HJ, Koopman WJ. Suppression of rheumatoid factor production by methotrexate in patients with rheumatoid arthritis. Evidence for differential influences of therapy and clinical status on IgM and IgA rheumatoid factor expression. Arthritis Rheum 1990;33:

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<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770> 2012 개원의와함께하는임상강좌 경희대학교의학전문대학원류마티스내과학교실 홍승재 진단의중요성 치료의첫단계 : 정확한진단은아무리강조해도지나치지않음 감별진단의중요성 : 진단이달라짐에따라치료시기와약제의선택, 진행경과, 합병증여부, 예후및삶의질에차이가있다. 류마티스관절염 (Rheumatoid arthritis) : 비교적젊은나이에발병하며, 진단초기부터관절염증에의한골파괴소견이가능함.