高分辨率外周骨定量CT評估類風濕關節炎患者TNFα抑製劑治療3個月的骨超微結構改變
背景：
骨侵蝕通常在類風濕關節炎（RA）起病後的頭幾個月內出現，為不可逆性病變。高分辨率外周骨定量CT（HR-pQCT）的分辨率高達81μm，已經成為評估RA骨質改變的有價值的工具。曾有研究報道RA患者在腫瘤壞死因子α（TNFα）抑製劑治療1年後的骨侵蝕進展極少，但尚無研究探討TNFα抑製劑治療開始後的極早期骨質變化。
目的：
TNFα抑製劑治療3個月後，利用HR-pQCT、放射X線片和3T MRI檢測RA患者掌指關節（MCP）和腕關節在骨超微結構和骨侵蝕進展方麵的早期變化。
方法：
26例RA患者在基線和治療3個月後分別接受腕關節3T MRI和MCP、腕關節的HR-pQCT檢測，僅在基線時進行X線檢查。在基線和治療3個月時分別評價28個關節疾病活動度評分（DAS28）。患者被分成兩組：TNFα抑製劑組和甲氨蝶呤（MTX）單藥組。用既往研發出來的方法在HR-pQCT中計算侵蝕體積、關節體積/寬度和骨微結構等參數。關節破壞則在X線和MRI圖像上利用Sharp評分和RAMRIS評分分別計算。
結果：
TNFα抑製劑組的患者相對年輕，基線DAS28評分更高，但性別比例、體重指數和病程長短等指標和MTX單藥組相似（表格）。從基線到治療後3個月，TNFα抑製劑組的DAS評分顯著改善（圖A）。HR-pQCT在基線時共檢出骨侵蝕75處。TNFα抑製劑組的MCH3侵蝕體積從基線到治療後3個月顯著下降（MCH2和腕關節均有下降趨勢）。相反，MTX單藥組的疾病活動度雖低，但MCH2和腕關節的侵蝕體積顯著增加（圖B）。TNFα抑製劑組的MCP關節間隙寬度和關節體積從基線到治療後3個月顯著縮小，與侵蝕體積變化呈正相關。TNFα抑製劑組的腕關節和MCP微結構參數基本上沒有變化，但侵蝕體積改變與骨小梁骨密度（BMD）變化呈顯著負相關（圖C）。HR-pQCT參數與RAMRIS評分或DAS評分之間未發現明顯的相關性。
結論：
我們發現TNFα抑製劑治療能在前3個月的治療中防止骨侵蝕進展和骨超微結構退化。HR-pQCT可作為敏感有效的檢測工具，即使在短期內也能量化骨質改變，監測RA的治療。
原文
ASSESSMENT OF 3-MONTH CHANGES IN BONEMICROSTRUCTURE UNDER ANTI-TNFα THERAPY IN PATIENTSWITH RHEUMATOID ARTHRITIS USING HR-PQCT
T. Shimizu 1 , H.J. Choi 1 , U. Heilmeier 1 , M. Tanaka 1 , A.J. Burghardt 1 , J. Gong 1 ,
N. Chanchek 1 , T.M. Link 1 , J. Graf 2 , J.B. Imboden 2 , X. Li 1 .1 Department of Radiology & Biomedical Imaging, Musculoskeletal Quantitative Imaging Research;
2 Department of Medicine, Division of Rheumatology, University of California San Francisco, San Francisco, United States
Background:
Bone erosions are usually thought to be irreversible and occur inthe first few months of RA onset. With its resolution of up to 81 μm, HR-pQCThas emerged as valuable tool to assess bone changes in RA (1,2) . Although oneprevious study showed minimal erosive progression in patients with RA one yearafter TNFα inhibition therapy(3) , no studies have investigated yet the very earlybone changes after the initiation of anti-TNFα treatment.
Objectives:
To investigate the early changes in bone erosion progression andbone microarchitecture in the MCP joints and wrist of RA patients using HR-pQCT,radiographs, and 3T MRI after 3 months of anti-TNFα treatment.
Methods:
26 RA patients underwent 3T MRI wrist scans and HR-pQCT scansof the MCP and wrist joints at baseline (BL) and at 3 months (3M). Radiographswere obtained at the baseline time point only. DAS28 was assessed at BL and 3M. Patients were divided into two groups: the anti-TNFα group and the MTX-only group.HR-pQCT-derived erosion volume, joint volume/width and bone microarchitectural parameters were computed using methods previously developed (4–6) , and the joint destruction was assessed via Sharp and RAMRISscorings using radiographs and MR images respectively.
Results:
Patients in the Anti-TNFα group were slightly younger than patients inthe MTX only group and had a higher initial DAS28 score,but otherwise displayedsimilar anthropometerics and demographics (Table).DAS scores significantly improved in the anti-TNFα group from BL to 3M (Fig. A).75 erosions were identified at BL by HR-pQCT. The anti-TNFα group showed a significant decrease of erosion volume from BL to 3M at MCH3 (with decreasing trend at MCH2 and wrist). The MTX-only group in contrast, displayed significant increases in erosion volume at MCH2 and wrist despite low disease activity (Fig. B). In the anti TNFα group, joint space width and volume of the MCP joints decreased significantly from BL to 3M and were positively correlated with erosion volume changes. Although microstructural parameters at the wrist and MCP remained largely unchanged, erosion volume changes were significantly negatively correlated with changes of trabecular BMD in the anti-TNFα group (Fig. C). No significant correlations were observed between HR-pQCT parameters and RAMRIS and DAS scores.
Conclusions:
We found that anti-TNFα treatmentcan prevent erosion progressionand deterioration of bone microarchitecture within the first 3 months of treatment.HR-pQCT can serve as a sensitive and powerful tool to quantify bone changes and monitor RA treatment even over short time periods.
References:
[1] Barnabe C et al. Nat Rev Rheumatol. 2015.
[2] Tam LS et al. J Rheumatol. 2016.
[3] Moller U et al. Ann Rheum Dis. 2009.
[4] Srikhum W et al. J Rheumatol. 2013.
[5] Yang H et al. Int J Rheum Dis. 2015.
[6] Burghardt AJ et al. Ann Biomed Eng. 2013.
Acknowledgements: The study was supported by UCB Pharma Inc.
Disclosure of Interest: None declared
DOI: 10.1136/annrheumdis-2017-eular.532
