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[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.

MTX单药治疗临床疗效良好但放射学进展的早期RA患者的预测因素和临床意义

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

背景：在早期RA患者中，数项随机对照试验显示MTX+TNF拮抗剂疗效优于单用MTX。然而，这些研究也指出部分患者使用MTX单药治疗，疗效良好。在SWEFOT试验中，所有患者在试验的起初3-4个月使用MTX单药治疗，达到低疾病活动度的患者不进入随机对照试验部分。我们之前报道了这部分患者的比例约为30%。在另一篇文章中，我们报道了这些患者经过2年治疗，疗效良好，但部分仍有放射学进展。在此，我们观察了这一队列的放射学进展情况及预测因素。

目的：分析SWEFOT试验中对初始MTX单药治疗反应良好及未进入随机试验的患者的放射学变化。

方法：共有487例早期RA（症状持续时间<1年）患者初始使用MTX治疗，并迅速增量至20mg/周以上。3-4个月后，147例患者DAS28<3.2，未进入随机对照试验，而继续使用MTX，每3个月评估一次。将这些患者进行分析。由2名经验丰富的阅片者进行Van der Heijde 改良的Sharp评分（SvdH）。比较不同时间的评分采用Wilcoxon配对检验。共有114例患者完成了放射学检查。

结果：在基线期，总SvdH评分(均值±SEM)为3.8±0.7（中位数: 1，IQR: 0-5）。1年后，上升至6.0±0.8（4，0-8；与基线期相比，p<0.0001），2年后，上升至7.9±0.9（4，0-8；与基线期和1年时相比，p<0.0001）。骨侵蚀评分与关节腔狭窄评分均显著进展。2年后总评分为3.9±0.7（2，0-6）。在基线期，48.1%患者没有X线损害（总评分=0）；1年后无X线损害的患者比例为26.9%，2年后为20.2%。15%患者总评分升高超过10。与RF阴性患者相比，RF阳性患者进展更大（4.78±0.91 (2，0-7) vs 1.90±0.78 (0，0-5)；p=0.067）分别为和。ACPA阳性与阴性患者相比，差异较小，且无统计学意义。RF和ACPA均阳性的患者放射学进展最大，为5.27±1.21（2，0-9）。RF单阳性患者比ACPA单阳性患者进展更大。男性比女性在数值上进展更大（5.00±1.05[2, 0-9] vs 3.08±0.88 [1, 0-3]; p=0.119）。

结论：MTX单药初始治疗早期RA的3～4个月疗效良好，但是DAS28<3.2的患者经过2年MTX单药治疗后放射学进展显著（从数值来看放射学进展属于中度）。放射学进展与RF阳性、RF和ACPA双阳性相关。半数患者在基线期没有损害，但其中大部分在2年后出现损害。

MTX初期临床疗效良好并不能排除之后放射学严重进展的结局。