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

Hanyang University Seoul Hospital

Status and phase: Not yet enrolling; Phase 4

Conditions: Axial Spondyloarthritis; Ankylosing Spondylitis

Treatments: Biological: Golimumab; Biological: Biological: Etanercept and its biosimilars; Biological: Infliximab biosimilar; Biological: Adalimumab and its biosimilars

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05164198

HC21C0076

Details and patient eligibility

About

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.

Enrollment: 448 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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448 participants in 2 patient groups

Open-label reduced-dose TNFi

Experimental group

Description:

Participants in the experimental arm will receive one of the intervention below according to the TNFi agent used at baseline: 1. Adalimumab 40mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48. 2. Etanercept 50mg subcutaneous every 10 days (Q10D) from week 0 to week 48. 3. Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 5 weeks (Q5W) from week 0 to week 48. 4. Remsima SC 120mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48.

Treatment:

Biological: Adalimumab and its biosimilars

Biological: Infliximab biosimilar

Biological: Golimumab

Biological: Biological: Etanercept and its biosimilars

Open-label full-dose TNFi

Active Comparator group

Description:

Participants in the comparator arm will receive one of the intervention below according to the TNFi agent used at baseline: 1. Adalimumab 40mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48. 2. Etanercept 50mg subcutaneous every week (QW) from week 0 to week 48. 3. Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 4 weeks (Q4W) from week 0 to week 48. 4. Remsima SC 120mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48.

Treatment:

Biological: Adalimumab and its biosimilars

Biological: Infliximab biosimilar

Biological: Golimumab

Biological: Biological: Etanercept and its biosimilars