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Does ACPA-negative RA consist of subgroups related to sustained DMARD-free remission and serological markers at disease presentation? Comment on article by Boeters DM et al.
Arthritis Research & Therapy ( IF 4.4 ) Pub Date : 2020-01-31 , DOI: 10.1186/s13075-020-2106-5
Alfonse T Masi 1 , Roy Fleischmann 2
Affiliation  

Letter to the Editor

We read with interest the article by Boeters DM et al. [1]. We would like to clarify the significant findings and suggest further research needed to validate the novel conclusion. In ACPA-negative patients, 1 sustained DMARD-free remission (SDFR) occurred over 5 years follow-up in 17 (6%) with baseline low (< 30) MBDA score vs approximately 50% remissions in both moderate (30–44) and high (> 44) MBDA score patients ([1], Fig. 1). All ACPA-positive RA patients had low percentages of SDFR and no difference was found by baseline MBDA score category [1]. Percentages of 3 MBDA categories did not differ (p = 0.470) between the ACPA-positive and ACPA-negative groups [1].

SDFR was recently reported by ACPA-negative vs ACPA-positive patients in the total Leiden early arthritis cohort (1993–2016; n = 1296) [2], from which the Boeters et al. study [1] was the most recent inclusion subgroup (2011–2016). In the total inclusion period (1993–2011), SDFR occurred between 5 and 15% in ACPA-positive RA vs 40 to 50% in the ACPA-negative RA [2], as in Boeters et al. [1].

Unexpectedly, in multivariate analyses ([1], Table 2), the 95 ACPA-negative RA patients with high (> 44) baseline scores had greater DMARD-free remission than the 17 reference patients with low (< 30) MBDA scores (p = 0.041). If MBDA were truly a marker of disease activity, one might expect low rather than high MBDA to predict SDFR. Alternatively, if ACPA-negative RA does consist of subgroups [1], its documentation will require further serological study in separate cohorts [2, 3] or search for genetic markers [3]. Confounding variables should be excluded, possibly clinical features related to age at onset, which was found to be a significant (p = 0.036) predictor of SDFR ([1], Table 2) and other disease variables not studied. Is it conceivable that this anomaly [1] is due to chance occurrence in a small sample size study leading to an incorrect conclusion, especially when borderline (p = 0.041) statistical correlation is found [1]?

A critical review of the value of multibiomarker disease activity score to predict remission in RA was recently published [4]. The challenging question is whether or not baseline MBDA (or serological markers) are being overinterpreted or overstated with respect to outcomes (or disease subgroups) was critically analyzed [4].

Data are in published article and reference citations.

  1. 1.

    Boeters DM, Burgers LE, Sasso EH, Huizinga TWJ, van der Helm-van Mil AHM. ACPA-negative RA consists of subgroups: patients with high likelihood of achieving sustained DMARD-free remission can be identified by serological markers at disease presentation. Arthritis Res Ther. 2019;21:1–9.

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    Matthijssen XM, Niemantsverdriet E, Huizinga TW, van der Helm-van Mil AHM. ACPA-positive patients benefited more than ACPA-negative patients; 25 year results of a longitudinal cohort study. Presentation 2871 at the 2019 American College of Rheumatology Meeting, Atlanta GA (pps 5098–5100 in <https://acrabstracts.org/wp-content/uploads/2019/10/2019-Abstract-Supplement.pdf>).

  3. 3.

    Hedström AK, Rönnelid J, Klareskog L, Alfredsson L. Complex relationships of smoking, HLA-DRB1 genes, and serologic profiles in patients with early rheumatoid arthritis: update from a Swedish population-based case-control study. Arthritis Rheumatol. 2019;71:1504–11.

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    Fleischmann R. Value of the multibiomarker of disease activity score to predict remission in RA: what does the evidence show? J Rheumatol. 2019;46:443–6.

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No acknowledgements or conflict of interest.

No funding contributed to the statements in the letter.

Affiliations

  1. Department of Medicine, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL, USA
    • Alfonse T. Masi
  2. Co-Medical Director Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, 8144 Walnut Hill Lane Suite 810, Dallas, TX, 75231, USA
    • Roy Fleischmann
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  1. Search for Alfonse T. Masi in:
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  2. Search for Roy Fleischmann in:
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Contributions

Both authors contributed to interpretation of published and comments in Letter. Both authors read and approved the final manuscript.

Corresponding author

Correspondence to Alfonse T. Masi.

Ethics approval and consent to participate

Letter refers to published article without new subjects.

Consent for publication

Both authors agree to publication.

Competing interests

The authors declare that they have no competing interests.

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Masi, A.T., Fleischmann, R. Does ACPA-negative RA consist of subgroups related to sustained DMARD-free remission and serological markers at disease presentation? Comment on article by Boeters DM et al.. Arthritis Res Ther 22, 17 (2020). https://doi.org/10.1186/s13075-020-2106-5

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  • DOI: https://doi.org/10.1186/s13075-020-2106-5

Keywords

  • Rheumatoid arthritis
  • Anti-citrullinated protein antibody (ACPA)
  • Multi-biomarker disease activity (MBDA) score
  • Remission

中文翻译：
ACPA阴性RA是否由与持续性DMARD缓解和疾病表现时血清学指标相关的亚组组成？评论Boeters DM等人的文章。

给编辑的一封信

我们感兴趣地阅读了Boeters DM等人的文章。[1]。我们想澄清重要的发现，并建议进行进一步的研究以验证新结论。在ACPA阴性患者中，在5年随访中有1例持续DMARD无症状缓解（SDFR），其中17例（6％）基线低（<30）MBDA评分，而中度（30-44）均为约50％缓解MBDA评分高的患者（> 44）（[1]，图1）。所有ACPA-阳性RA患者SDFR的低比例，并没有差异基线MBDA评分类别[1]找到。 ACPA阳性组和ACPA阴性组之间3种MBDA类别的百分比没有差异（p = 0.470）[1]。

最近在全部莱顿早期关节炎队列中（1993-2016；n  = 1296）[2]，ACPA阴性和ACPA阳性患者报道了SDFR [2]。研究[1]是最近的纳入亚组（2011-2016年）。在整个纳入期间（1993年至2011年），SDFR发生在ACPA阳性RA的5％至15％之间，而ACPA阴性RA的40％至50％[2]，如Boeters等人所述。[1]。

出乎意料的是，在多变量分析中（[1]，表2），基线得分高（> 44）的95位ACPA阴性RA患者比17位MBDA得分低（<30）的参考患者具有更高的DMARD无缓解率（p  = 0.041）。如果MBDA确实是疾病活动的标志，人们可能会期望MBDA值低而不是高来预测SDFR。另外，如果ACPA阴性RA确实由亚组组成[1]，则其文献将需要在不同的人群中进行进一步的血清学研究[2、3]或寻找遗传标记[3]。应当排除混杂变量，可能与发病年龄有关的临床特征很明显（p = 0.036）SDFR的预测因子（[1]，表2）和其他尚未研究的疾病变量。可以想象这种异常[1]是由于在小样本量研究中偶然发生而导致错误的结论，尤其是当发现边界线（p  = 0.041）统计相关性[1]时？

最近发表了关于多种生物标志物疾病活动评分对RA缓解预测价值的评论[4]。具有挑战性的问题是，是否严格分析了基线MBDA（或血清学标志物）相对于结局（或疾病亚组）是否被过度解释或夸大了[4]。

数据在已发表的文章和参考文献中。

  1. 1。

    Boeters DM，Burgers LE，Sasso EH，Huizinga TWJ，van der Helm-van Mil AHM。ACPA阴性的RA由亚组组成：在疾病表现时，可通过血清学标志物识别出实现持续无DMARD缓解的高可能性患者。关节炎治疗。2019; 21：1–9。

    • 文章
    • 谷歌学术
  2. 2。

    Matthijssen XM，Niemantsverdriet E，Huizinga TW，van der Helm-van Mil AHM。ACPA阳性患者比ACPA阴性患者受益更多。一项纵向队列研究的25年结果。在2019年美国风湿病学院会议上的演讲2871，佐治亚州亚特兰大（pps 5098-5100 in <https://acrabstracts.org/wp-content/uploads/2019/10/2019-Abstract-Supplement.pdf>）。

  3. 3。

    HedströmAK，RönnelidJ，Klareskog L，Alfredsson L.早期类风湿性关节炎患者吸烟，HLA-DRB1基因和血清学特征的复杂关系：来自瑞典一项基于人群的病例对照研究。风湿病关节炎。2019; 71：1504-11。

    • 文章
    • 谷歌学术
  4. 4。

    Fleischmann R.疾病活动评分的多种生物标志物对RA缓解的预测价值：证据表明了什么？J风湿病。2019; 46：443–6。

    • 文章
    • 谷歌学术

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隶属关系

  1. 美国伊利诺伊州皮奥里亚市伊利尼大道一号，伊利诺伊大学医学院皮奥里亚分校医学系
    • 阿方斯·马西（Alfonse T. Masi）
  2. 美国得克萨斯大学西南医学中心Metroplex临床研究中心联合医学总监，美国德克萨斯州达拉斯市8144 Walnut Hill Lane 810套房，美国德克萨斯州75231
    • 罗伊·弗莱希曼（Roy Fleischmann）
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引用本文

Masi，AT，Fleischmann，R. ACPA阴性RA是否由与疾病呈报时持续的DMARD缓解和血清学标志物相关的亚组组成？通过Boeters DM等人于文章评论关节炎那里Res 22， 17（2020）。https://doi.org/10.1186/s13075-020-2106-5

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  • DOI ：https ：//doi.org/10.1186/s13075-020-2106-5

关键词

  • 类风湿关节炎
  • 抗瓜氨酸化蛋白抗体（ACPA）
  • 多种生物标志物疾病活动度（MBDA）评分
  • 缓解
更新日期：2020-01-31
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