原文

譯文

[1392] - Radiological Progression in Patients with Early RA and a Good Clinical Response to MTX Monotherapy: Predictors and Clinical Implications.

Hamed Rezaei ¹, Ronald Van Vollenhoven, MD, PhD²,Kristina Forslind³,Kristina Albertsson¹,Helena Wallin¹,Pierre Geborek⁴,Sofia Ernestam¹,Ingemar Petersson⁵,Johan Bratt¹. ¹Karolinska University Hospital,²Rheumatology Unit, Karolinska University Hospital, Stockholm,³Helsingborgs Hospital,⁴Lund University Hospital,⁵Spenshult Hospital

Background: In patients with early RA, several randomized trials have demonstrated the superiority of methotrexate (MTX) + anti-TNF over MTX alone. However, these trials also showed that some patients did have excellent responses to MTX monotherapy. In the SWEFOT trial, all patients were given an initial 3-4 months trial period with MTX alone; patients achieving a low disease activity state with this treatment were not randomized in the controlled portion of the trial. We previously demonstrated that this was the case for appr. 30% of the patients. In a separate report (Wallin et al, abstract submitted) we showed that these patients had an excellent clinical course during the first two years, but that some radiological progression did nonetheless occur. Here, we investigated specific details of and predictors for radiological progression in this cohort.
Objective: To analyze in detail the radiological course in patients from the SWEFOT study who responded adequately to initial MTX monotherapy and who were not included in the randomized trial.
Methods: A total of 487 patients with early RA (symptom duration <1 year) were started on MTX at a rapidly escalating dosage up to at least 20 mg/week. After 3-4 months, the 147 patients who had a DAS28<3.2 were not randomized but continued on MTX and followed in “regular care”, including 3-monthly assessments. These patients were analyzed here. Van der Heijde modified Sharp scores (SvdH) were done by two experienced readers. Scores at different times were compared by Wilcoxon paired test. Complete x-ray data were available for 114 patients.
Results: At baseline, the mean±SEM total SvdH score (median, IQR) was 3.8±0.7 (1, 0-5). After 1 year, it had increased to 6.0±0.8 (4, 0-8; p<0.0001 vs. baseline) and after 2 years to 7.9±0.9 (4, 0-8; p<0.0001 vs both BL and 1 year). Highly significant progression was seen for both erosion score and joint space narrowing score. The increase in total score after 2 years was 3.9±0.7 (2, 0-6). At baseline, 48.1% of patients had no x-ray damage (total score= 0); at 1 year 26.9%, and at 2 years 20.2%. An increase in total score > 10, was seen in 15% of patients. RF positive patients had a trend towards greater progression than RF-negative ones: 4.78±0.91 (2, 0-7) vs. 1.90±0.78 (0, 0-5; p=0.067). For ACPA positive vs. negative, a smaller, non-significant difference was seen. Double-positive patients had the highest progression: 5.27±1.21 (2, 0-9). Single-positive RF had significantly higher progression than single-positive ACPA. Men had numerically more progression than women (5.00±1.05 (2, 0-9) vs 3.08±0.88 (1, 0-3; p=0.119).
Conclusions: Patients who responded to an initial 3-4 months trial of MTX monotherapy with a DAS28<3.2 showed statistically significant (but on average numerically modest) radiological progression during the first 2 years of disease. Progression was associated with RF- and double-positivity. About half of all patients had no damage at baseline but the majority of these did develop damage over 2 years.

An initial good clinical response to MTX does not preclude a less favorable radiological course.

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MTX單藥治療臨床療效良好但放射學(xué)進(jìn)展的早期RA患者的預(yù)測(cè)因素和臨床意義

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Rezaei H, et al. ACR 2010. Present No: 1392.

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背景：在早期RA患者中，數(shù)項(xiàng)隨機(jī)對(duì)照試驗(yàn)顯示MTX+TNF拮抗劑療效優(yōu)于單用MTX。然而，這些研究也指出部分患者使用MTX單藥治療，療效良好。在SWEFOT試驗(yàn)中，所有患者在試驗(yàn)的起初3-4個(gè)月使用MTX單藥治療，達(dá)到低疾病活動(dòng)度的患者不進(jìn)入隨機(jī)對(duì)照試驗(yàn)部分。我們之前報(bào)道了這部分患者的比例約為30%。在另一篇文章中，我們報(bào)道了這些患者經(jīng)過2年治療，療效良好，但部分仍有放射學(xué)進(jìn)展。在此，我們觀察了這一隊(duì)列的放射學(xué)進(jìn)展情況及預(yù)測(cè)因素。

目的：分析SWEFOT試驗(yàn)中對(duì)初始MTX單藥治療反應(yīng)良好及未進(jìn)入隨機(jī)試驗(yàn)的患者的放射學(xué)變化。

方法：共有487例早期RA（癥狀持續(xù)時(shí)間<1年）患者初始使用MTX治療，并迅速增量至20mg/周以上。3-4個(gè)月后，147例患者DAS28<3.2，未進(jìn)入隨機(jī)對(duì)照試驗(yàn)，而繼續(xù)使用MTX，每3個(gè)月評(píng)估一次。將這些患者進(jìn)行分析。由2名經(jīng)驗(yàn)豐富的閱片者進(jìn)行Van der Heijde 改良的Sharp評(píng)分（SvdH）。比較不同時(shí)間的評(píng)分采用Wilcoxon配對(duì)檢驗(yàn)。共有114例患者完成了放射學(xué)檢查。

結(jié)果：在基線期，總SvdH評(píng)分(均值±SEM)為3.8±0.7（中位數(shù): 1，IQR: 0-5）。1年后，上升至6.0±0.8（4，0-8；與基線期相比，p<0.0001），2年后，上升至7.9±0.9（4，0-8；與基線期和1年時(shí)相比，p<0.0001）。骨侵蝕評(píng)分與關(guān)節(jié)腔狹窄評(píng)分均顯著進(jìn)展。2年后總評(píng)分為3.9±0.7（2，0-6）。在基線期，48.1%患者沒有X線損害（總評(píng)分=0）；1年后無X線損害的患者比例為26.9%，2年后為20.2%。15%患者總評(píng)分升高超過10。與RF陰性患者相比，RF陽性患者進(jìn)展更大（4.78±0.91 (2，0-7) vs 1.90±0.78 (0，0-5)；p=0.067）分別為和。ACPA陽性與陰性患者相比，差異較小，且無統(tǒng)計(jì)學(xué)意義。RF和ACPA均陽性的患者放射學(xué)進(jìn)展最大，為5.27±1.21（2，0-9）。RF單陽性患者比ACPA單陽性患者進(jìn)展更大。男性比女性在數(shù)值上進(jìn)展更大（5.00±1.05[2, 0-9] vs 3.08±0.88 [1, 0-3]; p=0.119）。

結(jié)論：MTX單藥初始治療早期RA的3～4個(gè)月療效良好，但是DAS28<3.2的患者經(jīng)過2年MTX單藥治療后放射學(xué)進(jìn)展顯著（從數(shù)值來看放射學(xué)進(jìn)展屬于中度）。放射學(xué)進(jìn)展與RF陽性、RF和ACPA雙陽性相關(guān)。半數(shù)患者在基線期沒有損害，但其中大部分在2年后出現(xiàn)損害。

MTX初期臨床療效良好并不能排除之后放射學(xué)嚴(yán)重進(jìn)展的結(jié)局。