Introduction: Ankylosing spondylitis is a chronic inflammatory disorder which primarily affects the axial skeleton, the major characteristic of the disease being the early involvement of the sacroiliac joints. The condition manifests by chronic inflammatory back pain and, as the disease progresses, patients will develop extreme impairment of spinal mobility because of spinal fusion. Case presentation: A 66-year-old man, diagnosed with HLA-B27-positive ankylosing spondylitis, permanent atrial ﬁbrillation, ischemic cardiac disease, arterial hypertension, type 2 diabetes mellitus and stage 3A chronic kidney disease, was admitted for cervicalgia radiated to both shoulders and bilateral mechanical gonalgia. His son was also diagnosed with ankylosing spondylitis at the age of 29 years. Regarding the history of ankylosing spondylitis treatment, initially, the patient was prescribed nonsteroidal antiinflammatory drugs (NSAIDs); because of the inadequate response to NSAIDs, biological therapy with an anti-TNF agent was initiated (Infliximab). Fifteen months after the initiation of Infliximab, the patient presented with worsening symptoms; anti-Infliximab antibodies were detected, therefore he was switched to another anti-TNF agent, Adalimumab. Upon current admission, the clinical examination revealed thoracic kyphosis and marked limitation of cervical and lumbar spine mobility. Blood tests revealed mild anemia, inflammatory syndrome and azotate retention. The pelvic X-ray showed grade 3-4 bilateral sacroiliitis. The continuation of treatment with Adalimumab and Sulfasalazine was decided, with close monitoring of the patient. Conclusions: Ankylosing spondylitis is a multisystem inflammatory disorder, whose natural course includes periods of flares and remission. The peculiarity of this case consists in the early development of anti-Infliximab antibodies (secondary non-responder).