Allergy, Immunology & Rheumatology Division, University of Rochester Medical Center, Rochester, New York, USA
Rheumatology, Allergy & Clinical Immunology Division, University of California, Davis, Shriners Hospital, Sacramento, California, USA.
BMJ. 2021 Jan 4;372:m4447. doi: 10.1136/bmj.m4447.
Axial spondyloarthritis (axSpA) is an inflammatory disease of the axial skeleton associated with significant pain and disability. Previously, the diagnosis of ankylosing spondylitis required advanced changes on plain radiographs of the sacroiliac joints. Classification criteria released in 2009, however, identified a subset of patients, under the age of 45, with back pain for more than three months in the absence of radiographic sacroiliitis who were classified as axSpA based on a positive magnetic resonance imaging or HLAB27 positivity and specific clinical features. This subgroup was labeled non-radiographic (nr)-axSpA. These patients, compared with those identified by the older New York criteria, contained a larger percentage of women and demonstrated less structural damage. However, their clinical manifestations and response to biologics were similar to radiographic axSpA. The discovery of the interleukin (IL) IL-23/IL-17 pathway revealed key molecules involved in the pathophysiology of axSpA. This discovery propelled the generation of antibodies directed toward IL-17A, which are highly effective and demonstrate treatment responses in axSpA that are similar to those observed with anti-TNF agents. The finding that agents that block IL-23 were not effective in axSpA came as a surprise and the potential underlying mechanisms underlying this lack of response are discussed. New agents with dual inhibition of the IL-17A and F isoforms and some oral small molecule agents that target the Jak-STAT pathway, have also shown efficacy in axSpA.
强直性脊柱炎(axSpA)是一种与严重疼痛和残疾相关的中轴骨骼炎症性疾病。以前,骶髂关节炎的影像学进展是诊断强直性脊柱炎的必要条件。然而,2009 年发布的分类标准确定了年龄在 45 岁以下、无影像学骶髂关节炎但有三个月以上背痛的患者亚组,根据磁共振成像(MRI)阳性或 HLA-B27 阳性和特定临床特征,将其归类为 axSpA。这一亚组被标记为非放射学(nr)-axSpA。与用旧的纽约标准识别的患者相比,这些患者中女性比例更高,且结构损伤较少。然而,他们的临床表现和对生物制剂的反应与放射学 axSpA 相似。白介素(IL)IL-23/IL-17 通路的发现揭示了 axSpA 病理生理学中涉及的关键分子。这一发现推动了针对 IL-17A 的抗体的产生,这些抗体在 axSpA 中非常有效,并且与抗 TNF 药物观察到的反应相似。令人惊讶的是,阻断 IL-23 的药物在 axSpA 中无效,并且讨论了缺乏这种反应的潜在潜在机制。具有 IL-17A 和 F 型双重抑制作用的新药物和一些针对 Jak-STAT 通路的口服小分子药物也已显示出在 axSpA 中的疗效。