Despite the progress in the treatment of ankylosing spondylitis (AS), a significant number of patients do not achieve low disease activity (LDA). The aim of the study is to estimate the size of unmet needs in the treatment of AS in a long-term observational study. Between January 2003 and December 2017, 220 patients with radiographic SpA were evaluated fulfilling the ASAS criteria. They were followed up at predefined times and were naive to biological treatment with anti-tumor necrosis factor agents (anti-TNFs) and the interleukin (IL)-17 inhibitor. NSAIDs, all anti-TNFs and the IL-17 inhibitor secukinumab were used according to the European, United States and Canadian guidelines for AS. During follow-up, several clinical parameters including disease activity scores were recorded. All 220 patients had an active disease and received at least two NSAIDs for 3 months. The anti-TNF of first choice was infliximab-51%, followed by adalimumab-27% and etanercept-22%. During follow-up, 22 patients were excluded from the study (18 lost, 4 never received anti-TNF due to comorbidities). From the rest (198), 12 did not receive anti-TNFs (8 due to sustained LDA on NSAIDs solely and 4 due to treatment denial). Finally, 186 (94%) were treated with anti-TNFs demonstrating sustained long-term LDA. However, 16 patients never achieved LDA despite they received two or three anti-TNFs or the IL-17 inhibitor. Thus, a total of 20 (10.1%) patients never achieved LDA. This is the first study aiming to estimate the gap and the size of unmet needs in AS patients using the international guidelines and recommendations for AS treatment, which is 10.1%.