van der Heijde Désirée, Kartman Cynthia E, Xie Li, Beattie Scott, Schlichting Douglas, Mo Daojun, Durez Patrick, Tanaka Yoshiya, Fleischmann Roy
D. van der Heijde, MD, PhD, Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
C.E. Kartman, RN, S. Beattie, PhD, D. Mo, MD, PhD, Eli Lilly and Company, Indianapolis, Indiana, USA;
J Rheumatol. 2022 Feb;49(2):133-141. doi: 10.3899/jrheum.210346. Epub 2021 Sep 15.
To evaluate the effect of baricitinib on inhibiting radiographic progression of structural joint damage over 5 years in patients with active rheumatoid arthritis (RA).
Patients completed 1 of 3 phase III baricitinib trials (ClinicalTrials.gov: NCT01711359, NCT01710358, or NCT01721057) and entered the long-term extension RA-BEYOND (NCT01885078), in which patients received once-daily 4 mg or 2 mg baricitinib. Across these trials, patients initially receiving methotrexate (MTX) or adalimumab (ADA) switched to baricitinib 4 mg at Week 52. Patients initially receiving placebo (PBO) switched to baricitinib 4 mg at Week 24. Radiographs were scored at baseline and Years 2, 3, 4, and 5. Change from baseline in van der Heijde modified total Sharp score (ΔmTSS) was computed.
Overall, 2125 of 2573 (82.6%) randomized patients entered RA-BEYOND; 1837 of 2125 (86.4%) entered this analysis. From Years 3 to 5, higher proportions of disease-modifying antirheumatic drug (DMARD)-naïve patients on initial baricitinib (monotherapy or with MTX) had no progression vs initial MTX (ΔmTSS ≤ 0 at Year 5: 59.6% baricitinib 4 mg; 66.2% baricitinib 4 mg + MTX; 40.7% MTX). Higher proportions of patients with inadequate response (IR) to MTX on initial baricitinib or ADA vs PBO had no progression (ΔmTSS ≤ 0 at Year 5: 54.8% baricitinib 4 mg; 55.0% ADA; 50.3% PBO). Higher proportions of patients with conventional synthetic DMARD-IR on initial baricitinib 4 mg had less progression vs initial PBO or baricitinib 2 mg (ΔmTSS ≤ 0 at Year 5: 66.7% baricitinib 4 mg; 58.2% baricitinib 2 mg; 60.0% PBO).
Oral baricitinib maintained lower levels of radiographic progression than initial conventional synthetic DMARD or PBO through 5 years in patients with active RA.
评估巴瑞替尼对活动期类风湿关节炎(RA)患者5年内抑制关节结构损伤影像学进展的效果。
患者完成3项巴瑞替尼III期试验中的1项(ClinicalTrials.gov:NCT01711359、NCT01710358或NCT01721057),并进入长期扩展试验RA-BEYOND(NCT01885078),其中患者接受每日一次4mg或2mg巴瑞替尼治疗。在这些试验中,最初接受甲氨蝶呤(MTX)或阿达木单抗(ADA)治疗的患者在第52周换用4mg巴瑞替尼。最初接受安慰剂(PBO)治疗的患者在第24周换用4mg巴瑞替尼。在基线以及第2、3、4和5年时对X线片进行评分。计算范德海伊德改良总夏普评分(ΔmTSS)相对于基线的变化。
总体而言,2573例随机分组患者中有2125例(82.6%)进入RA-BEYOND;2125例中有1837例(86.4%)进入本分析。从第3年到第5年,初始接受巴瑞替尼(单药治疗或联合MTX)的未使用过改善病情抗风湿药物(DMARD)的患者无进展的比例高于初始接受MTX的患者(第5年时ΔmTSS≤0:4mg巴瑞替尼组为59.6%;4mg巴瑞替尼+MTX组为66.2%;MTX组为40.7%)。初始接受巴瑞替尼或ADA治疗而非PBO治疗的对MTX反应不足(IR)的患者中,无进展的比例更高(第5年时ΔmTSS≤0:4mg巴瑞替尼组为54.8%;ADA组为55.0%;PBO组为50.3%)。初始接受4mg巴瑞替尼治疗的对传统合成DMARD反应不足的患者中,病情进展小于初始接受PBO或2mg巴瑞替尼治疗的患者(第5年时ΔmTSS≤0:4mg巴瑞替尼组为66.7%;2mg巴瑞替尼组为58.2%;PBO组为60.0%)。
在活动期RA患者中,口服巴瑞替尼在5年内维持的影像学进展水平低于初始传统合成DMARD或PBO。