Modern technological advances have led to the identification of several novel non-MHC genes that may hold clues to a better understanding of the pathogenesis of AS. Two of the most promising new genes are the ERAP1 gene encoding aminopeptidase 1, an enzyme present in the endoplasmic reticulum involved in cutting peptides for loading onto class I MHC molecules, and the interleukin 23 receptor (IL-23R) gene that encodes for the IL23R expressed on the TH17 cells.13 The ERAP1 association is seen primarily in HLA B-27–positive patients, bringing back the arthritogenic peptide theory; whereas, the UPR and homodimer formation described above has been shown to increase IL-23 production, implicating TH 17-positive cells in the pathogenesis. In a mouse model, a novel CD3 and ROR γT positive, but CD4 and CD8 negative T cell population bearing the IL-23 receptor was recently described.14 The IL-17 and IL-22 secreted by these cells could explain the inflammatory and the osteoproliferative manifestations of spondyloarthritis, respectively.14 The importance of the IL-17 pathway in the pathogenesis of spondyloarthritis has led to investigations of IL-17 inhibitors in the treatment of AS.
Limited Treatment Options
Compared with RA, axSpA patients have limited treatment options, although the choices are increasing.
Most treatment studies in axSpA have been conducted in AS population and not in nr-axSpA patients. Unlike RA, nonsteroidal antiinflammatory drugs (NSAIDs) have a major role to play in the treatment of axSpA; whereas, the disease-modifying antirheumatic drugs (DMARDs) have a very limited role.15 A majority of axSpA patients show a very good (50% improvement or better) response to NSAIDs. The only DMARD to show limited efficacy in the treatment of axSpA has been sulfasalazine, which may be useful only in treating peripheral arthritis.15 Methotrexate and leflunomide have shown no efficacy on either axial or peripheral joint disease, but it is not uncommon to find these DMARDs being used to treat AS patients.
After physical therapy and NSAIDs have failed to give sufficient relief to patients, TNFi are used.15 Five TNFi (i.e., etanercept, infliximab, adalimumab, golimumab and certolizumab) have been approved by the FDA for the treatment of AS, and they all show remarkable similarity in their efficacy in relieving the important symptoms of axSpA. Studies have shown that TNFi improve health-related quality of life, patient-reported outcomes, anemia, sleep quality, fatigue, bone density and even forced vital capacity in patients with AS.16-20 Elevated levels of C-reactive protein and evidence of osteitis on SI joint MRI scan are predictors of a good response to TNFi therapy. However, as mentioned previously, no TNFi has been approved to treat either nr-axSpA or the entire spectrum of axSpA.
