REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)

Multicenter, Prospective Clinical Trial for Optimizing TNF Inhibitor Dose Adjustment in Ankylosing Spondylitis Patients With Stable Disease Activity

Participants maintaining stable disease activity of Ankylosing Spondylitis (AS) with standard-dose tumor necrosis factor inhibitor (TNFi) treatment will randomly split into two groups: maintaining standard-dose TNFi, versus reduced-dose TNFi. The proportion of participants not underwent flare between the two groups will be analyzed.

Inclusion Criteria:

• Documented diagnosis of Ankylosing spondylitis (AS) and meet the modified New York classification criteria for AS.
• Subjects maintaining stable disease (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] < 4) with standard-dose subcutaneous tumor-necrosis factor inhibitor (TNFi) treatment during previous 6 months from screening.
• Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 at screening and 12 weeks prior to screening
• In subjects treated with methotrexate or sulfasalazine, the dose should be maintained (methotrexate≤ 25mg/day, sulfasalazine ≤ 3 g/day) during previous 4 weeks before screening.
• In subjects treated with systemic glucocorticoids, the dose should be less than 10mg/day of predinisolone or equivalent during at least 2 weeks from the screening
• Subjects with stable dose of concomitant NSAID (including Cox2 inhibitors) during the 2 weeks from the randomization

Exclusion Criteria:

• Exposure to more than 1 TNFi

• History of hypersensitivity reaction to any TNFis

• Subjects with concomitant fibromyalgia, as determined by the investigator

• Subjects who have received any TNFis with reduced dosage

• Presence of total spinal ankylosis ('Bamboo spine')

• Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study

• Subjects with a history of malignancies and lymphoproliferative disorder including lymphoma within 5 years (Basal cell carcinoma treated within previous 3 months and showing no evidence of recurrence, actinic keratosis, and treated cervical/colon carcinoma in situ were allowed.)

• Subjects with current or history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac or neurological disease, as determined by the investigator

• Subjects with significant laboratory abnormalities included but not limited to:

  1. AST/ALT > 3.0 X ULN
  2. White blood cell (WBC) < 3000/μL and/or absolute neutrophil count (ANC) < 1500/μL
  3. Platelet count <100,000/μL and/or hemoglobin level <8.5 g/dL
  4. Serum creatinine ≥ 1.5 X ULN

• Subjected with any high-potency opioids (ex. methadone, hydromorphone, morphine, oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, meperidine)

• Subjects with current acute or chronic viral hepatitis B or C or with human immunodeficiency virus (HIV) infection

• Subjects planning to receive any live attenuated vaccinations after screening

• Subjects has history of chronic alcohol abuse or drug abuse within 6 months from screening

• Subjects concomitantly treated with systemic glucocorticoid (>10mg/day of prednisolone or equivalent doses)

• Subjects with any other condition that, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study