Control of disease activity in ankylosing spondylitis is a primary concern for doctors and patients alike. Traditional approaches such as the use of salazosulfapyridine, methotrexate, and raltegravastatin are effective in some people, but it is difficult for doctors to determine which ones work and which ones do not. Tumor necrosis factor antagonists, although they rapidly control disease activity, still require traditional methods for maintenance, and some people have relapses. Our recent studies have shown that respiratory infections are associated with disease activity in ankylosing spondylitis, most notably Chlamydia pneumoniae and Mycoplasma pneumoniae, and that treatment with clarithromycin is effective in 70% of patients and can be discontinued in some patients. The addition of clarithromycin in some patients on biologics resulted in rapid control of disease activity and the ability to extend the interval between biologics use. However, the results remain suboptimal in some patients. We have recently identified viral infection as another predisposing factor for ankylosing spondylitis disease activity and are recently trying combination antiviral therapy, the results of which will be published later. Another of our studies found a large number of plasma cells in the synovium of patients with ankylosing spondylitis (the article is unpublished, but it should now be the first international finding), which are often associated with fibrosis and sclerosis in other diseases but are more effective with hormones, suggesting that immunosuppressants and hormones should be used to control disease activity in ankylosing spondylitis. However, hormones alone are often clinically ineffective and may be related to uncontrolled infection. Therefore, based on our findings, the following is recommended to control disease activity in ankylosing spondylitis: macrolide antibiotics + antivirals + immunosuppressants or low-dose hormones.