Vicente-Rabaneda Esther F, Atienza-Mateo Belén, Blanco Ricardo, Cavagna Lorenzo, Ancochea Julio, Castañeda Santos, González-Gay Miguel Á
Rheumatology Division, Hospital Universitario de la Princesa, IIS-Princesa, C/Diego de León 62, 28006 Madrid, Spain.
Rheumatology Division, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla 25, 39008 Santander, Cantabria, Spain.
Autoimmun Rev. 2021 Jun;20(6):102830. doi: 10.1016/j.autrev.2021.102830. Epub 2021 Apr 19.
Interstitial lung disease (ILD) is a serious complication that represents the second leading cause of death in patients with rheumatoid arthritis (RA). Treatment of RA-ILD remains controversial. The absence of randomized clinical trials and specific ACR or EULAR therapeutic guidelines makes it difficult to establish solid therapeutic recommendations on this issue. In this scenario, real-world data is especially valuable.
To review the literature evidence on the efficacy and safety of abatacept (ABA) for the treatment of rheumatoid arthritis (RA) with associated interstitial lung disease (ILD), given its clinical relevance and the lack of consensus on its therapeutic management.
PUBMED and EMBASE were searched from the date of approval of ABA to the end of 2020 using a combination of RA, ILD and ABA terms following PRISMA guidelines. Identified studies were evaluated by two independent investigators.
Nine original studies (1 case series and 8 observational studies) were selected for inclusion in the systematic review. No randomized trial or meta-analysis were identified. The mean age of patients ranged from 61.2 to 75 years and the mean RA duration varied from 7.4 to 18 years. Subcutaneous ABA (74.5%-91%) predominated in combination with conventional synthetic DMARDs (csDMARDs) (58%-75%), and it was used as first-line biologic agent in 22.8%-64.9% of the patients. The mean course of ILD ranged from 1 to 6.7 years, being usual and nonspecific interstitial pneumonia the most frequent patterns. Improvement or stabilization of ILD imaging (76.6%-92.7%) and FVC or DLCO (>85%) was described after a mean follow-up of 17.4-47.8 months, regardless of the pattern of lung involvement, being more remarkable in patients with shorter evolution of ILD. ABA led to significantly lower ILD worsening rates than TNF inhibitors (TNFi) and was associated with a 90% reduction in the relative risk of deterioration of ILD at 24 months of follow-up compared to TNFi and csDMARDs. Combination with methotrexate may have a corticoid-sparing effect. No unexpected adverse events were identified.
Current evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD. It would be highly desirable to develop prospective randomized controlled studies to confirm these findings.
间质性肺病(ILD)是类风湿关节炎(RA)患者中导致死亡的第二大主要原因,是一种严重的并发症。RA-ILD的治疗仍存在争议。由于缺乏随机临床试验以及美国风湿病学会(ACR)或欧洲抗风湿病联盟(EULAR)的具体治疗指南,因此难以就该问题制定可靠的治疗建议。在这种情况下,真实世界的数据尤其有价值。
鉴于阿巴西普(ABA)在治疗类风湿关节炎(RA)合并间质性肺病(ILD)方面的临床相关性以及在治疗管理上缺乏共识,回顾关于其疗效和安全性的文献证据。
按照系统评价与Meta分析的首选报告项目(PRISMA)指南,结合RA、ILD和ABA等检索词,在从ABA获批之日至2020年底的时间段内对PubMed和EMBASE进行检索。由两名独立研究人员对纳入的研究进行评估。
9项原始研究(1项病例系列研究和8项观察性研究)被选入该系统评价。未检索到随机试验或Meta分析。患者的平均年龄在61.2至75岁之间,RA的平均病程为7.4至18年。皮下注射ABA(74.5%-91%)与传统合成改善病情抗风湿药(csDMARDs)联合使用较为普遍(58%-75%),并且在22.8%-64.9%的患者中被用作一线生物制剂。ILD的平均病程为1至6.7年,常见和非特异性间质性肺炎是最常见的类型。在平均随访17.4-47.8个月后,无论肺部受累类型如何,ILD影像学表现改善或稳定(76.6%-92.7%)以及用力肺活量(FVC)或一氧化碳弥散量(DLCO)改善(>85%),在ILD病程较短的患者中更为显著。与肿瘤坏死因子抑制剂(TNFi)相比,ABA导致ILD病情恶化率显著降低,并且与TNFi和csDMARDs相比,在随访24个月时ILD恶化的相对风险降低了90%。与甲氨蝶呤联合使用可能具有糖皮质激素节省效应。未发现意外不良事件。
目前的证据表明,ABA可能是治疗合并ILD的RA患者的一种合理选择。开展前瞻性随机对照研究以证实这些发现非常必要。