Unlike RA, in which the structural damage refers to the catabolic changes of loss of cartilage and bony erosions, axSpA leads to catabolic plus anabolic changes in the form of syndesmophytes and ankylosis of the joints. The initial studies of two years of treatment with TNFi failed to show a reduction in new bone formation, although these studies were criticized for using a historical control group and for being of inadequate duration. It did start a debate on whether the new bone formation is uncoupled from the underlying inflammatory process. Careful analysis of prospective data on spinal MRI shows that, in some patients, the early inflammatory changes of osteitis can progress to fatty infiltration, which can be the precursor of new bone formation. Research has identified several important mediators in this process, such as bone morphogenic proteins, molecules in the SMAD and WNT signaling pathways, that could be targeted for future therapies to prevent osteoproliferation.21 Adequate doses of NSAIDs (blocking prostaglandin E2, a molecule that acts synergistically with WNT) and more recently long-term (i.e., longer than four years) treatment with TNFi (eliminating osteitis before fatty changes) have been shown to reduce the rate of new bone formation in patients with AS, but not in nr-axSpA.22,23
Trials of abatacept, rituximab and tocilizumab, all approved for the treatment of RA, have yielded insignificant results with regard to efficacy in AS patients.24-26 It’s encouraging to note that the IL-17 pathway is now being targeted for manipulation. Secukinumab a monoclonal antibody against IL-17A and ustekinumab blocking the P40 subunit of IL-12/IL-23 have shown efficacy in proof-of-principle studies for the treatment of AS.27-28 Apremilast, a small molecule inhibiting phosphodiesterase E4 (unrelated to the IL-17 pathway), is also being studied in phase 3 trials in AS.
The ACR, the Spondylitis Association of America and Spondyloarthritis Research & Treatment Network are developing treatment recommendations for axSpA, and these are expected to be completed by the end of 2014.
Tasks Ahead
Although significant progress continues to be made in defining the spectrum of axial spondyloarthritis, its epidemiology, genetics and management, several questions remain unanswered.
MRI scan of the SI joints has been vital in early diagnosis, but its role in monitoring disease progression or response to treatment is uncertain.
Whether a combination therapy of NSAIDs with TNFi or new biologics is better in achieving remission and preventing osteoproliferation remains to be seen.
Personalized treatment can be possible only by improved understanding of genetics and baseline characteristics predicting response.
