Winthrop Kevin L, Bathon Joan, Kerschbaumer Andreas, Isaacs John D, Mease Philip, Gottenberg Jaque-Eric, Crow Mary K, Kay Jonathan, Crofford Leslie, Baraliakos Xenofon, Bykerk Vivian, Siebert Stefan, Kloppenburg Margreet, Aletaha Daniel, McInnes Iain B, Huizinga Thomas, Voll Reinhard, Gravallese Ellen M, Breedveld Ferdinand C, van Vollenhoven Ronald, Smolen Josef S
Oregon Health and Science University, Portland, OR, USA.
Division of Rheumatology, Columbia University, New York, NY, USA.
Ann Rheum Dis. 2025 Apr 15. doi: 10.1016/j.ard.2025.02.009.
The Advances in Targeted Therapies annual meeting brings together experts within the field of rheumatology and immunology to highlight and discuss the latest scientific developments and needs in the field. The objective is to highlight unmet scientific needs in the field of rheumatology.
The 24th annual Advances in Targeted Therapies meeting convened with more than 100 international clinicians and scientific researchers in rheumatology, immunology, and other specialities relating to all aspects of immune-mediated inflammatory diseases. During the meeting, we held 5 rheumatologic disease-specific discussion sections consisting of experts in each field. These groups included rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), osteoarthritis (OA), and systemic lupus erythematosus (SLE). In each group, experts were asked to identify the top 2 to 3 most important overarching and disease-specific scientific unmet needs to be addressed in the next 5 years.
The overarching themes across disciplines included the need for precision medicine, improved classification of disease states, and the further identification of targets and associated therapies, including the potential role of chimeric antigen receptor (CAR) T cell therapies. Within RA, the group highlighted the lack of precision medicine and the need for better biomarkers. Further, the lack of targeted therapies against fibroblasts in RA was discussed, with the potential impact of targeting fibroblasts early in the disease as an unmet need. For PsA, there is a continued need for a better definition of disease endotypes and for the categorisation of those with complex and difficult-to-treat (D2T) diseases. The development of bispecific molecules and combination therapeutic approaches remain a high priority. For axSpA, the disease-modifying characteristics of nonsteroid anti-inflammatory drugs need further evaluation, as does the treatment of residual pain and fatigue frequently in the disease. In OA, new therapeutic targets remain an unmet need, and the discussion group prioritised potential experimental strategies that could lead to innovative therapeutic targets. Elucidating the specific signalling and target cells responsible for, or inhibiting, repair will be essential for developing targeted therapies. SLE experts emphasised the need to identify the most predictive biological contributions to disease progression in patients with early clinical precursors of SLE. The role of CAR T cell therapy must be further investigated, along with ancillary biologic studies (eg, immune system profiling) that provide critical insights into disease pathogenesis. Further, there is a need to determine the relationship of patient-relevant symptoms to the pathophysiology of SLE and identify new therapeutic targets for these symptoms.
There remain many unmet needs on the road to precision medicine with regard to identifying disease endotypes and biomarkers for disease progression or therapeutic response. For most diseases discussed, a strong unmet need remains with regard to identifying new targets and therapies for those with refractory or D2T disease. The ability to prevent or cure rheumatic disease remains the ultimate unmet need in rheumatology.
“靶向治疗进展”年度会议汇聚了风湿病学和免疫学领域的专家，以突出和讨论该领域的最新科学进展及需求。目的是强调风湿病领域尚未满足的科学需求。
第24届“靶向治疗进展”年度会议召集了100多名国际临床医生以及风湿病学、免疫学和与免疫介导的炎症性疾病各方面相关的其他专业领域的科研人员。会议期间，我们举办了5个特定风湿病的讨论环节，每个领域都有专家参与。这些小组包括类风湿关节炎（RA）、银屑病关节炎（PsA）、中轴型脊柱关节炎（axSpA）、骨关节炎（OA）和系统性红斑狼疮（SLE）。在每个小组中，专家们被要求确定未来5年需要解决的2至3个最重要的总体及特定疾病的科学未满足需求。
各学科的总体主题包括对精准医学的需求、疾病状态分类的改进以及进一步确定靶点和相关疗法，包括嵌合抗原受体（CAR）T细胞疗法的潜在作用。在类风湿关节炎领域，该小组强调了精准医学的缺乏以及对更好生物标志物的需求。此外，还讨论了类风湿关节炎中针对成纤维细胞的靶向治疗的缺乏，将在疾病早期靶向成纤维细胞的潜在影响作为未满足需求。对于银屑病关节炎，持续需要更好地定义疾病内型以及对复杂且难以治疗（D2T）疾病患者进行分类。双特异性分子和联合治疗方法的开发仍然是高度优先事项。对于中轴型脊柱关节炎，非甾体抗炎药的疾病修饰特性需要进一步评估，该疾病中经常出现的残余疼痛和疲劳的治疗也需要评估。在骨关节炎中，新的治疗靶点仍然是未满足需求，讨论小组将可能导致创新治疗靶点的潜在实验策略列为优先事项。阐明负责或抑制修复的特定信号传导和靶细胞对于开发靶向疗法至关重要。系统性红斑狼疮专家强调需要确定对系统性红斑狼疮早期临床前驱患者疾病进展最具预测性的生物学因素。必须进一步研究CAR T细胞疗法的作用，以及提供对疾病发病机制关键见解的辅助生物学研究（例如免疫系统分析）。此外，需要确定与患者相关的症状与系统性红斑狼疮病理生理学的关系，并确定针对这些症状的新治疗靶点。
在精准医学的道路上，在确定疾病内型和疾病进展或治疗反应的生物标志物方面仍有许多未满足的需求。对于所讨论的大多数疾病，在为难治性或D2T疾病患者确定新靶点和疗法方面，仍存在强烈的未满足需求。预防或治愈风湿性疾病的能力仍然是风湿病学最终的未满足需求。
