Low dose etanercept for the treatment of patients with ankylosing spondylitis

• Register: ISRCTN
• Last refreshed on: 7 November 2016
• Main ID: ISRCTN45278838
• Date of registration: 21/01/2011
• Prospective Registration: No
• Primary sponsor: Norfolk and Norwich University Hospital NHS Foundation Trust (UK)
• Public title: Low dose etanercept for the treatment of patients with ankylosing spondylitis
• Scientific title: An open label, pilot, multicentre, stepdown, randomised controlled trial to examine whether etanercept 25 mg once weekly is effective in maintaining a clinical response in patients with ankylosing spondylitis who have responded to 50 mg once weekly
• Date of first enrolment: 18/10/2010
• Target sample size: 50
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN45278838
• Study type: Interventional
• Study design: Multicentre randomised open label controlled interventional treatment trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

United Kingdom

Contacts

• Name: Frances Elender

Key inclusion & exclusion criteria

Inclusion criteria: At screening/baseline:
The participant will be placed on etanercept 50 mg once weekly providing:
1. Diagnosis of AS according to the modified New York criteria
2. Confirmation of sustained active spinal disease, demonstrated by:
2.1. BASDAI score of at least 4 units
2.2. At least 4 cm on a 0-10cm spinal pain visual analogue scale (VAS)
2.3. Both severity measures demonstrated on two occasions at least 12 weeks apart without any change of treatment
3. Conventional treatment with two or more NSAIDs taken sequentially at maximum tolerated or recommended dosage for 4 weeks have failed to control symptoms
4. Participant has clinically acceptable results from laboratory screening test
5. Male or Female, aged 18 - 80 years
6. Participant is willing and able to give informed consent to participate in the study
7. Able (in the Investigators opinion) and willing to comply with all study requirements

At randomisation:
The participant will be randomised to 50 mg or 25 mg etanercept providing:
1. An adequate response to treatment has been achieved, with response defined as:
1.1. Reduction of the BASDAI score to 50% of the pre-treatment value, or
1.2. Reduction in BASDAI by 2 or more units, and
1.3. Reduction of the spinal pain VAS by 2 cm or more
2. The participant finds etanercept acceptable and wishes to continue treatment
Exclusion criteria: At screening/baseline:
The participant will not enter the study if ANY of the following apply:
1. Previous treatment with any licensed or experimental anti TNF therapy
2. Chronic infection of the upper respiratory tract (e.g. sinusitis), chest (e.g. bronchiectatic lung disease), urinary tract or skin (e.g. paronychia, chronic ulcers, open wounds)
3. Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months
4. Any ongoing or active infection or any major episode of infection requiring hospitalisation or treatment with intravenous (IV) antibiotics within the preceding 30 days and/or orally administered antibiotics in the preceding 15 days
5. Received any live (attenuated) vaccines within four weeks of screening visit
6. Known immunosuppressive disease or treatment with immunosuppressive drugs
7. Active/latent tuberculosis as identified by local screening guidelines
8. Stable corticosteroid use 10 mg OD taken in the 4 weeks prior to screening
9. History of hepatitis B or C
10. Significant concurrent cardiovascular disease including; uncompensated congestive heart failure, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension
11. Cancer or a history of cancer (other than resected cutaneous basal cell carcinoma, and in situ cervical cancer) within five years of entering the screening period
12. Significant renal or hepatic impairment
13. Leukopaenia (WBC less than 3000 x 10^6/L) and/or neutropeania (WBC less than or equal to 1500 x 10^6/L)
14. Thrombocytopaenia (platelets less than 150 x 10^9/L)
15. Demyelinating disorders such as multiple sclerosis
16. Women who are pregnant, lactating or of childbearing potential not using contraception
17. Scheduled elective surgery/procedures requiring general anaesthesia during the study
18. Allergy to latex (the needle cover of the syringe contains latex)
19. Presence of any other significant and uncontrolled medical condition, which in the investigator's opinion precludes the use of etanercept
20. Unable to give informed consent
21. Unable/unwilling to comply with study procedures
22. Not available for followup assessments
23. Received treatment with an investigational drug within 12 weeks prior to study screening
24. History of back injury or trauma which confounds the clinical scenario

At randomisation:
The participant will not be randomised if ANY of the following apply:
1. An adequate response to etanercept 50 mg per week has not been achieved by the end of the 6 month lead in period
2. The participant wishes to discontinue treatment with etanercept
3. On the basis of adverse reactions, the treating physician considers the participant should withdraw from treatment with etanercept

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Topic: Musculoskeletal; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal
Musculoskeletal Diseases
Ankylosing spondylitis

Intervention(s)

Patients attending hospital rheumatology out-patient clinics who fulfil the NICE eligibility criteria for AS will be initiated on Etanercept (Enbrel®) 50 mg once weekly. After a six month lead-in phase, responders to Etanercept (as defined by NICE criteria) will be randomly assigned to either step down to 25 mg once weekly dose or continue with 50 mg once weekly.

Follow up length: 6 months
Study entry: single randomisation only

Primary Outcome(s)

Maintenance of 50% reduction in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and/or fall by greater than or equal to 2 units at 3 and 6 months post-randomisation

Secondary Outcome(s)

1. AS response criteria (ASAS 20,40,5 of 6 & Partial Remission)
2. Bath Ankylosing Spondylitis Metrology Index (BASMI)
3. Bath Ankylosing Spondylitis Functional Index (BASFI)
4. Ankylosing Spondylitis Quality of Life Questionnaire. (ASQoL)
5. Standard measure of health outcome (EQ-5D)
6. Proportions of patients discontinuing therapy for different reasons

All secondary outcome measures will be measured at the same time point as the primary outcome measure (i.e. BASDAI) which is one year post baseline (6 months post randomisation).

Secondary ID(s)

2010-020913-10

9375

Source(s) of Monetary Support

Pfizer (formerly Wyeth) (UK)