Ixekizumab as subcutaneous injection is in clinical development for people with radiographic and non-radiographic axial spondyloarthritis who have not responded favourably to previous non-steroidal anti-inflammatory drug (NSAID) therapy. Axial spondyloarthritis is a chronic form of arthritis that causes significant inflammatory low back and/or buttock pain that persists more than three months. The condition affects the bones and joints at the base of the spine where it connects with the pelvis. When the disease is active, these joints become inflamed. Axial spondyloarthritis is divided into two sub-groups depending on whether the clear structural damage can (radiographic) or cannot (non-radiographic) be seen using radiographic imaging.
Ixekizumab is an engineered antibody designed to bind and obstruct the pro-inflammatory interleukin-17A (IL-17A) signalling molecule. It has been suggested that IL-17 may be a crucial mediator of inflammation in the pathway that leads to the development and progression of axial spondyloarthritis. By blocking this pathway, ixekizumab may help prevent joint inflammation, bone erosion, and bone fusion in a patient population where few alternative therapies exist in instances of previous treatment failure.
Upadacitinib acts by selectively blocking a protein called Janus-Associated Kinase 1 (JAK1 and JAK1/3). JAKs contribute to the processes within the cell to produce an immune or inflammatory response. There is an emerging body of evidence establishing that JAK dependent enzymes are major contributors to the progression of immunemediated diseases such as AS and that blocking such enzymes can be beneficial. Upadacitinib is taken orally and if licensed, it will offer an additional treatment option for patients with active AS.