Effectiveness and Safety of Acemetacin in Active Axial Spondyloarthritis: A Real-world Study

This is a prospective, multicenter, observational real-world study to evaluate the effectiveness and safety of acemetacin in patients with active axial spondyloarthritis (axSpA).

Background Axial spondyloarthritis is a chronic inflammatory disease primarily affecting the axial skeleton, characterized by inflammatory back pain, morning stiffness, enthesitis, and peripheral arthritis, with possible extra-articular manifestations such as uveitis and psoriasis. The disease predominantly affects young males aged 20-30 years and can lead to persistent pain, progressive spinal immobility, and substantial disability if not adequately treated. The estimated prevalence of axSpA in mainland China is approximately 0.3%, affecting over 4 million individuals. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line therapy by major international and Chinese clinical practice guidelines. Acemetacin is a prodrug NSAID that is metabolized to indomethacin in vivo, with a potentially favorable gastrointestinal safety profile due to reduced direct mucosal irritation. However, prospective real-world evidence evaluating its effectiveness across different axSpA phenotypes - radiographic (r-axSpA) versus non-radiographic (nr-axSpA) - and disease durations remains limited.

Study Design This study enrolls 150 adults aged 18-65 years who fulfill the 2025 ASAS-SPARTAN revised axSpA classification criteria with an ASDAS score >2.1. Key exclusion criteria include hypersensitivity to acemetacin or other NSAIDs, active or recurrent gastrointestinal ulceration or bleeding, severe cardiac/renal/hepatic insufficiency, inflammatory bowel disease, and use of systemic glucocorticoids, intra-articular corticosteroid injections, or targeted therapies within 3 months before enrollment. Stable use of conventional synthetic DMARDs (e.g., sulfasalazine) initiated more than 3 months prior is permitted.

After a screening period of up to 7 days, eligible participants receive acemetacin 90 mg orally once daily for 4 weeks. A telephone follow-up is conducted at week 2, and an in-clinic visit at week 4. Early termination visits are scheduled within 3 days of the last dose for participants who discontinue prematurely.

Endpoints The primary endpoint is: the mean change from baseline in overall pain VAS score at week 4, and differences across predefined subgroups. Secondary endpoints include: (1) the proportion of patients achieving clinical remission (ASDAS ≤1.3) or low disease activity (1.3<ASDAS≤2.1) at week 4; (2) changes from baseline in pain VAS, BASDAI, BASFI, ASAS Health Index, and BASMI at weeks 2 and 4; and (3) changes from baseline in CRP and ESR at week 4. All secondary endpoints are also analyzed across subgroups. Safety is assessed by monitoring adverse events graded per CTCAE v5.0, with special attention to gastrointestinal and cardiovascular events.

Statistical Considerations Based on an assumed standard deviation of 2 for the change in VAS pain score, with a two-sided significance level of 0.05 and 80% power, a minimum of 136 participants are required. Accounting for potential attrition, the planned enrollment is 150 participants.

Inclusion criteria

• Subjects who fully understand the purpose and procedures of the trial and voluntarily sign the Informed Consent Form (ICF);
• Subjects aged 18-65 years (inclusive), regardless of gender;
• Meet the 2025 ASAS-SPARTAN Revised Classification Criteria for Axial Spondyloarthritis;
• ASDAS score > 2.1.

Exclusion criteria

• Subjects with known allergy to acemetacin, other NSAIDs, or any excipients;
• Subjects with active gastrointestinal ulcer/bleeding, or a history of recurrent ulcer/bleeding;
• Subjects with severe cardiac or renal dysfunction, or hepatic dysfunction;
• Subjects with ulcerative colitis or Crohn's disease;
• Subjects who received systemic glucocorticoids or intra-articular glucocorticoid injections within 3 months prior to the study start;
• Subjects who received targeted therapy within 3 months prior to the study start;
• Any other condition that, in the investigator's opinion, makes the subject unsuitable for participation in this study.