Østergaard Mikkel, Wu Joseph, Fallon Lara, Sherlock Sarah P, Wang Cunshan, Fleishaker Dona, Kanik Keith S, Maksymowych Walter P
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Valdemar Hansens Vej 17, 2600, Glostrup, Copenhagen, Denmark.
Pfizer Inc, Groton, CT, USA.
Rheumatol Ther. 2023 Aug;10(4):1001-1020. doi: 10.1007/s40744-023-00564-y. Epub 2023 Jun 18.
This post hoc analysis of phase 2 trial data assessed the efficacy of tofacitinib on magnetic resonance imaging (MRI) outcomes with the detailed anatomy-based Canada-Denmark (CANDEN) MRI scoring system and evaluated tofacitinib suppression of spinal inflammation in patients with active ankylosing spondylitis (AS).
Patients with active AS (per modified New York criteria) were randomized 1:1:1:1 to receive tofacitinib 2, 5, or 10 mg twice daily (BID), or placebo, in a 16-week, phase 2, double-blind clinical trial. Spine MRI assessments were performed at baseline and week 12. For post hoc analysis, MRI images from patients receiving tofacitinib 5 or 10 mg BID, or placebo, were re-evaluated by two readers blinded to time point/treatment and assessed by the CANDEN MRI scoring system. Least squares mean changes from baseline to week 12 were reported for CANDEN-specific MRI outcomes, with analysis of covariance used for comparisons of pooled tofacitinib and tofacitinib 5 or 10 mg BID versus placebo. p values without multiplicity adjustment were reported.
MRI data from 137 patients were analyzed. At week 12, CANDEN spine inflammation score and vertebral body, posterior elements, corner, non-corner, facet joint, and posterolateral inflammation subscores were significantly reduced with pooled tofacitinib versus placebo (p < 0.0001; except non-corner subscore, p < 0.05). Total spine fat score was numerically increased with pooled tofacitinib versus placebo.
In patients with AS, tofacitinib treatment was associated with significant reductions in MRI scores of spinal inflammation versus placebo, as assessed by the CANDEN MRI scoring system. Tofacitinib reduced inflammation in posterolateral elements of the spine and facet joints, which has not been described previously.
ClinicalTrials.gov registry (NCT01786668).
这项对2期试验数据的事后分析，采用基于详细解剖结构的加拿大 - 丹麦（CANDEN）磁共振成像（MRI）评分系统评估托法替布对MRI结果的疗效，并评估托法替布对活动性强直性脊柱炎（AS）患者脊柱炎症的抑制作用。
在一项为期16周的2期双盲临床试验中，将符合改良纽约标准的活动性AS患者按1:1:1:1随机分组，分别每日两次（BID）接受2、5或10mg托法替布，或安慰剂治疗。在基线和第12周进行脊柱MRI评估。对于事后分析，由两名对时间点/治疗不知情的阅片者重新评估接受5或10mg BID托法替布或安慰剂治疗患者的MRI图像，并通过CANDEN MRI评分系统进行评估。报告了CANDEN特异性MRI结果从基线到第12周的最小二乘均值变化，采用协方差分析比较汇总的托法替布以及5或10mg BID托法替布与安慰剂的差异。报告了未进行多重性调整的p值。
分析了137例患者的MRI数据。在第12周时，汇总的托法替布组与安慰剂组相比，CANDEN脊柱炎症评分以及椎体、后部结构、角部、非角部、小关节和后外侧炎症子评分显著降低（p < 0.0001；非角部子评分除外，p < 0.05）。汇总的托法替布组与安慰剂组相比，脊柱总脂肪评分在数值上有所增加。
在AS患者中，根据CANDEN MRI评分系统评估，与安慰剂相比，托法替布治疗可使脊柱炎症的MRI评分显著降低。托法替布减少了脊柱后外侧结构和小关节的炎症，这在之前尚未有过描述。
ClinicalTrials.gov注册库（NCT01786668）。
