Spondyloarthropathy (SpA)

Arthritis Therapy Acceleration Programme

Ankylosing Spondylitis (AS) (also now known as Axial Spondyloarthritis or SpA) is an inflammatory disease affecting up to 0.3% of the population. Treatment options for SpA remain limited. First line therapy consists of physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs). Biological anti-tumour necrosis factor (TNF) and anti-interleukin (IL)-17A agents are second line options in patients with continued active disease. Patients who are refractory or intolerant to these two cytokine targets currently do not have access to any other approved therapies. The fact that only one third of SpA patients achieve disease remission with anti-TNF agents illustrates the significant unmet clinical need in SpA.

We wish to develop novel treatments for AS/SpA such as GM-CSF targeted therapy.

Our preclinical characterisation of the immuno-biology in SpA suggests that GM-CSF mediated inflammation may be important, there is therefore a strong rationale for exploring GM-CSF blockade as a novel therapeutic pathway in SpA.

We hypothesize that there is a distinct GM-CSF signature in the blood of some or all SpA patients, that this signature will be reversed by anti-GM-CSF treatment and that this will correlate with clinical response. We will study immune and bacterial signatures in blood and stool of patients before and after biologic treatments including anti-GMCSF. If signature reversal is seen in the absence of clinical response, we will confidently be able to rule out GM-CSF neutralization as a therapy for SpA (null hypothesis). Alternatively we hope to detect a “signature” that will predict good response to therapy in some (or all) individuals.   This would confirm the rationale of this treatment for further large studies and potentially pave the way for personalized therapy for AS/SpA patients in the future.

NHS Partners