TNFBA治疗强柱达8年的放射学评估

原文

译文

THU0497 RADIOGRAPHIC PROGRESSION IN ANKYLOSING SPONDYLITIS – RESULTS AFTER UP TO 8 YEARS OF ANTI-TNF TREATMENT X. Baraliakos 1,*, H. Haibel 2, J. Listing 3, J. Sieper 2, J. Braun 1 and DIKAS Study Group 1Rheumazentrum Ruhrgebiet, Herne, 2Charité - Campus Benj. Franklin, 3German Rheumatism Research Center, Berlin, Germany   Background: Therapy with TNF-blockers is clinically efficacious in patients with active ankylosing spondylitis (AS). Improvement of spinal inflammation was demonstrated by MRI but inhibition of radiographic progression has not been shown. Hypothetical considerations have suggested TNF blockers could worsen structural changes. Baseline (BL) radiographic damage is the only significant predictor for further radiographic progression in AS. Objectives: To compare the long-term course of radiographic changes in AS patients treated with infliximab (‘aTNF’) vs. a historical cohort (Herne cohort, ‘HC’), the latter patient group was retrospectively collected and never treated with TNF blockers. Methods: Overall, 22 patients were included in aTNF 34 in HC. The selection based only on the availability of lateral x-rays of the cervical and lumbar spine at BL and after 8 years. The radiographs, mostly performed in 2-year intervals, were scored by two blinded readers usingthe mSASSS in concealed time order. The expectation-maximation (EM) algorithm was used to impute missing radiographs at year 4. Mann-Whitney test was used for simple comparisons between both cohorts. ANCOVA was applied to compare radiographic progression between both cohorts after adjustment for BL status. The progression between year 4 and year 8 was compared by means of non-parametric ANCOVA and by taking the status at BL and the radiographic progression between BL and year 4 into account. Results: Patients in the aTNF group had higher BASDAI (6.2±1.4 vs 4.3±1.4 in HC) and BASFI (5.3±1.4 vs. 3.4±1.5, both p<0.0001) levels at BL. HC patients were older, had a longer disease duration and were less frequently HLA B27-positive. The degree of baseline radiographic damage was similar in both groups (13.2±17.6 in aTNF vs. 14.2±13.8 in HC, p=0.26). Both groups showed significant radiographic progression after 8 years (20.2±21.4 in aTNF and 25.9±17.8 in HC (both p<0.001). Similar radio­graphic progression was seen in the groups for the time between BL and year 4 of the study (4.1 units in aTNF and 4.3 units in HC (p=0.51). After adjustment for baseline mSASSS and for the rate of radiographic progression during the first 4 years, less radiographic progression between 4y and 8y was found in aTNF (2.9 units), vs. HC (7.4 units) (p=0.029). In contrast, adjusting for age (p=0.61), symptom duration (p=0.42), HLA-B27 (p=0.10), BASDAI (p=0.53) and BASFI (p=0.38) at BL did not significantly influence radiographic progression. The number of new syndes­mo­phytes/patient after 8 years in patients without BL-syndesmophytes did not differ between groups (0.8±1.6 in aTNF vs. 2.6±4.7 in HC, p=0.36). This was in contrast to the patients with BL-syndesmophytes: less new syndesmophytes developed in the aTNF group (1.3±4.5) vs. HC (3.3±1.9), (p=0.032). Conclusions: This study shows ongoing radiographic progression in patients with established AS over 8 years. Taking into account the relatively low patient numbers and the nature of the historical cohort, we think that it is fair to say that these data show no evidence that continuous anti-TNF therapy leads to increased radiographic progression in AS. It seems even possible that long-term anti-TNF therapy may decrease radiographic damage. This is also backed by the result that less new syndesmophytes developed in anti-TNF treated patients.

TNFBA治疗强柱达8年的放射学评估 X. Baraliakos, EULAR 2011. Present No: THU0497   背景：对于活动性强直性脊柱炎（AS）患者使用TNF拮抗剂治疗是临床有效的。MRI显示脊柱炎症改善但并未显示抑制放射学进展。假设TNF拮抗剂可能使结构改变恶化。对AS病人，基线的放射学损害是未来放射学进展唯一重要的预测因子。   目的：对使用英利昔单抗 (‘aTNF’) 治疗的AS患者和既往治疗组的AS患者 (Herne cohort, ‘HC’)，比较两组患者长期的放射学改变。后一组病人为回顾性收集并且从未用TNF拮抗剂治疗。   方法：aTNF组共22位患者，HC组共34位患者。选择有可使用的基线及8年后颈腰椎侧位X线片的患者。放射学摄片，大多是每二年一次，计分采用mSASSS评分系统，2名读片人，拍摄时间顺序为盲态。如果第4年缺失x线摄片，则使用最大期望值算法。两组间简单比较使用Mann-Whitney检验。调整基线状态后，使用协方差分析比较两组间放射性显像上病情的进展情况。第4年和第8年病情进展的情况使用非参数协方差分析方法进行比较，同时考虑基线状态以及基线与第4年放射学进展。   结果：与HC组相比，aTNF组患者在基线时有更高的BASDAI评分 (6.2±1.4 vs 4.3±1.4 HC组)和BASFI评分 (5.3±1.4 vs. 3.4±1.5 HC组)， p值均<0.0001。HC组病人年龄更大，病史更长，更低的HLA B27阳性率。两组的基线放射性显像损害相似(aTNF 组13.2±17.6 vs. HC组14.2±13.8, p=0.26)。两组于8年后均显示显著的放射学进展(aTNF组20.2±21.4 ，HC组25.9±17.8，p值均<0.001)。在从基线到研究的第4年期间，两组放射学进展程度相似(aTNF组4.1 单位，HC组4.3单位 p=0.51)。在按基线mSASSS评分和前4年放射性显像进展率调整后，从第4年到第8年期间，aTNF组 (2.9 单位) 放射学进展较HC 组(7.4单位)小(p=0.029)。相反，基线时的年龄(p=0.61)，症状持续时间(p=0.42)，HLA-B27 (p=0.10)，BASDAI (p=0.53) 和 BASFI (p=0.38)等因素没有明显影响放射学进展。基线没有韧带骨赘的患者中8年后发生新韧带骨赘数/人，两组间没有显著差异(aTNF组0.8±1.6 vs. HC组2.6±4.7, p=0.36)。与之相反，基线有韧带骨赘的患者形成的新韧带骨赘/人：aTNF 组 (1.3±4.5)比 HC组少 (3.3±1.9), (p=0.032)。   结论：本研究显示AS病人8年后放射学呈持续性进展。考虑到病例数相对较少以及既往治疗组的性质，我们认为可以说这些数据显示没有证据表明连续使用抗肿瘤坏死因子治疗会加重AS患者的放射学进展。似乎长期使用抗肿瘤坏死因子治疗还有可能减少放射学损害。同时支持这个结果，使用抗肿瘤坏死因子治疗的患者，新形成的韧带骨赘更少。