Novel combination therapy for rheumatoid arthritis: efficacy of anti-CD3 antibody enhanced by p38 inhibitor (Work packages 1-4)

抗CD3治疗有可能在短期治疗后对1型糖尿病患者产生持久疗效，如果将其转化为RA治疗，可以减少甚至消除对频繁生物治疗的需求，并带来所有相关的经济和医疗保健益处。然而，其进入临床的途径受到可变反应和副作用的阻碍，后者由炎性细胞因子释放引起。本申请概述了一项机制验证研究，以确定是否可以通过联合给予炎性结节激酶p38抑制剂减轻抗CD3治疗性抗体Otelixizumab（OTX）的副作用并增强临床应答。

Anti-CD3 therapy has the potential to have long-lasting efficacy for patients with type 1 diabetes following a brief course of therapy, which if translated to the treatment of RA could reduce or even remove the need for frequent biologic therapy with all the associated financial and healthcare benefits. However, its pathway into the clinic has been hampered by variable responses and side effects, the latter caused by inflammatory cytokine release. This application outlines a proof-of-mechanism study to determine whether the side effects of the anti-CD3 therapeutic antibody Otelixizumab (OTX) could be mitigated and clinical response enhanced, by co-administration of an inhibitor of the inflammatory nodal kinase p38.