McGill University, 5252 de Maisonneuve Blvd Ouest, 3D.57, Montreal, QC, H4A 3S5, Canada.
Johns Hopkins University, Baltimore, MD, USA.
Arthritis Res Ther. 2022 Apr 5;24(1):83. doi: 10.1186/s13075-022-02724-x.
Fatigue, a common symptom of rheumatoid arthritis (RA), is detrimental to health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on fatigue, sleep, and HRQoL and explored associations between fatigue, related patient-reported outcomes (PROs), and disease activity in RA patients.
This post hoc analysis pooled data from three Phase 3 studies of tofacitinib (ORAL Scan; ORAL Standard; ORAL Sync) in RA patients. Patients received tofacitinib 5 or 10 mg twice daily, placebo, or adalimumab (active control; ORAL Standard only, not powered for superiority) with conventional synthetic disease-modifying antirheumatic drugs. Assessed through Month (M)12 were changes from baseline in disease activity, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Medical Outcomes Study Sleep scale (MOS-SS), and Short Form-36 Health Survey (SF-36) composite/domain scores, and proportions of patients reporting improvements from baseline in FACIT-F total and SF-36 domain scores ≥ minimum clinically important differences (MCIDs) or ≥ population normative values. Pearson correlations examined associations among PROs at M6. Treatment comparisons were exploratory, with p < 0.05 considered nominally significant.
Generally, active treatment led to significant improvements from baseline in FACIT-F total, and MOS-SS and SF-36 composite/domain scores vs placebo, observed by M1 and maintained through M6 (last placebo-controlled time point). Through M6, more patients achieved improvements from baseline ≥ MCID and achieved scores ≥ population normative values in FACIT-F total and SF-36 domain scores with tofacitinib vs placebo. Through M12, some nominally significant improvements with tofacitinib vs adalimumab were observed. With active treatment at M6, FACIT-F scores were moderately (0.40-0.59) to highly (≥ 0.60) correlated with SF-36 composite/domain scores (particularly vitality), moderately correlated with most MOS-SS domain scores, and highly correlated with MOS-SS Sleep Problems Index I scores. Disease activity correlations were moderate with FACIT-F scores and low (0.20-0.39) to moderate with SF-36 general health domain/composite scores.
Tofacitinib and adalimumab generally conferred significant, clinically meaningful improvements in fatigue, sleep, and HRQoL (including vitality) vs placebo through M6, with improvements maintained to M12. M6 correlations between FACIT-F, PROs of sleep, HRQoL, and disease activity underscore the interrelatedness of multiple PROs and disease activity in RA.
ClinicalTrials.gov NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009).
疲劳是类风湿关节炎（RA）的常见症状，对健康相关生活质量（HRQoL）有害。我们评估了托法替尼对疲劳、睡眠和 HRQoL 的影响，并探讨了 RA 患者疲劳与相关患者报告结局（PROs）和疾病活动之间的关系。
这是托法替尼（ORAL Scan；ORAL Standard；ORAL Sync）三项 3 期研究的事后分析。患者接受托法替尼 5 或 10mg 每日两次、安慰剂或阿达木单抗（阳性对照；仅在 ORAL Standard 中，不具有优势）联合常规合成疾病修饰抗风湿药物治疗。在第 12 个月评估疾病活动、慢性疾病治疗疲劳功能评估量表（FACIT-F）、医疗结局研究睡眠量表（MOS-SS）和健康调查简表 36 项（SF-36）综合/域评分的变化，以及报告疲劳 FACIT-F 总分和 SF-36 域评分改善≥最小临床重要差异（MCID）或≥人群正常值的患者比例。在第 6 个月时，Pearson 相关性检验 PROs 之间的相关性。治疗比较是探索性的，p < 0.05 被认为具有名义显著性。
一般来说，与安慰剂相比，托法替尼在第 1 个月和第 6 个月（最后一个安慰剂对照时间点）开始时就显著改善了 FACIT-F 总分和 MOS-SS 和 SF-36 综合/域评分。通过第 6 个月，与安慰剂相比，托法替尼在疲劳的 FACIT-F 总分和 SF-36 域评分中实现了≥MCID 和≥人群正常值的改善的患者比例更高。在第 12 个月时，与阿达木单抗相比，托法替尼的一些结果具有统计学意义上的改善。在第 6 个月时使用托法替尼治疗，FACIT-F 评分与 SF-36 综合/域评分（尤其是活力）呈中度（0.40-0.59）至高度（≥0.60）相关，与大多数 MOS-SS 域评分中度相关，与 MOS-SS 睡眠问题指数 I 评分高度相关。与 FACIT-F 评分相关的疾病活动相关性为中度，与 SF-36 一般健康域/综合评分的相关性为低度（0.20-0.39）至中度。
托法替尼和阿达木单抗与安慰剂相比，通过第 6 个月通常能显著改善疲劳、睡眠和 HRQoL（包括活力），并持续到第 12 个月。第 6 个月时 FACIT-F、睡眠、HRQoL 和疾病活动的 PROs 之间的相关性强调了 RA 中多个 PROs 和疾病活动之间的相互关系。
ClinicalTrials.gov NCT00847613（注册：2009 年 2 月 19 日）；NCT00853385（注册：2009 年 3 月 2 日）；NCT00856544（注册：2009 年 3 月 5 日）。
