Trial Outcomes & Findings for Extension Study Evaluating Etanercept in Ankylosing Spondylitis (NCT NCT00410046)

NCT ID: NCT00410046

Last Updated: 2012-05-11

Results Overview

Healthcare resources were defined as hospital admissions, therapeutic warm baths, physiotherapist visits, and outpatient physician visits. Healthcare resource utilization was evaluated using a questionnaire asking patients whether or not they had used the healthcare resource during the 48 weeks preceding enrollment in study 0881A3-402 (NCT00247962) and during the 48 weeks of treatment in this extension study (0881A3-405).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 84 participants
• Primary outcome timeframe: 96 weeks
• Results posted on: 2012-05-11

Participant Flow

Patients were recruited in Europe from November 2006 to January 2008.

Patients in 0881A3-402 (NCT00247962) were randomized to receive etanercept (ETN) or sulphasalazine (SSZ). After completion, they were eligible for enrollment into this extension study and all patients received ETN. Outcome measure analysis kept the 0881A3-402 assignment of ETN or SSZ. This enabled an analysis of changes from the original baseline.

Participant milestones

Measure	Etanercept Patients received ETN dose 50 mg once weekly or Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into this study, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Overall Study STARTED	84
Overall Study COMPLETED	79
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	Etanercept Patients received ETN dose 50 mg once weekly or Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into this study, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	1
Overall Study Lost to Follow-up	1

Baseline Characteristics

Extension Study Evaluating Etanercept in Ankylosing Spondylitis

Baseline characteristics by cohort

Measure	Etanercept n=84 Participants Patients received ETN dose 50 mg once weekly or Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into this study, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Age Continuous	42.70 years STANDARD_DEVIATION 10.49 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants

PRIMARY outcome

Timeframe: 96 weeks

Population: All patients who took ETN and completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

Healthcare resources were defined as hospital admissions, therapeutic warm baths, physiotherapist visits, and outpatient physician visits. Healthcare resource utilization was evaluated using a questionnaire asking patients whether or not they had used the healthcare resource during the 48 weeks preceding enrollment in study 0881A3-402 (NCT00247962) and during the 48 weeks of treatment in this extension study (0881A3-405).

Outcome measures

Measure	Etanercept / ETN n=59 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Hospitalization 48 weeks before treatment	6 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Hospitalization during 48 treatment weeks	4 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Therapeutic warm bath 48 weeks before treatment	8 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Therapeutic warm bath during 48 treatment weeks	4 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Visit to physiotherapist 48 weeks before treatment	26 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Visit to physiotherapist during 48 treatment weeks	11 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Out-patient physician 48 weeks before treatment	40 patients	—
Number of Patients Using Healthcare Resources in the 48 Weeks Before and During Treatment Out-patient physician during 48 treatment weeks	30 patients	—

PRIMARY outcome

Timeframe: 96 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

Patients were asked whether or not they had taken sick leave during the 48 weeks preceding enrollment in study 0881A3-402 (NCT00247962) and during the 48 weeks of treatment in this extension study (0881A3-405).

Outcome measures

Measure	Etanercept / ETN n=59 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Number of Patients Taking Sick Leave in the 48 Weeks Before and During Treatment Sick leave 48 weeks before treatment	27 patients	—
Number of Patients Taking Sick Leave in the 48 Weeks Before and During Treatment Sick leave during 48 weeks of treatment	23 patients	—

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

Healthcare resources were defined as hospital admissions, therapeutic warm baths, physiotherapist visits, and outpatient physician visits. Healthcare resource utilization was evaluated using a questionnaire asking patients whether or not they had used the healthcare resource during the 48 weeks of treatment.

Outcome measures

Measure	Etanercept / ETN n=59 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=25 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Number of Patients Utilizing Healthcare Resources During 48 Weeks of Treatment Admissions to hospital	4 patients	2 patients
Number of Patients Utilizing Healthcare Resources During 48 Weeks of Treatment Therapeutic warm bath sessions	4 patients	4 patients
Number of Patients Utilizing Healthcare Resources During 48 Weeks of Treatment Physiotherapist visits	11 patients	6 patients
Number of Patients Utilizing Healthcare Resources During 48 Weeks of Treatment Out-patient physician visit	30 patients	10 patients

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into study 0881A3-405, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

Healthcare resources were defined as hospital admissions, therapeutic warm baths, physiotherapist visits, and outpatient physician visits. Healthcare resource utilization was evaluated using a questionnaire asking all patients whether or not they had used the healthcare resource during the 48 weeks of treatment, and if so, how many times the resource was used. The mean number of times is based on those patients who responded to the questionnaire stating they had utilized healthcare resources (see outcome measure 3).

Outcome measures

Measure	Etanercept / ETN n=59 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=25 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Number of Times Healthcare Resources Were Used Per Patient During 48 Weeks of Treatment Inpatient hospitalization days per patient	6.13 # of times utilized per patient Interval 0.5 to 12.0	2.75 # of times utilized per patient Interval 0.5 to 5.0
Number of Times Healthcare Resources Were Used Per Patient During 48 Weeks of Treatment Therapeutic warm bath sessions per patient	6.13 # of times utilized per patient Interval 0.5 to 15.0	14.00 # of times utilized per patient Interval 5.0 to 26.0
Number of Times Healthcare Resources Were Used Per Patient During 48 Weeks of Treatment Physiotherapist visits per patient	11.41 # of times utilized per patient Interval 0.5 to 30.0	16.58 # of times utilized per patient Interval 0.5 to 43.0
Number of Times Healthcare Resources Were Used Per Patient During 48 Weeks of Treatment Out-patient physician visit per patient	2.08 # of times utilized per patient Interval 0.5 to 10.0	2.4 # of times utilized per patient Interval 0.0 to 6.0

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

The impact of treatment on work productivity was assessed by sick leave. Patients were asked whether or not they had taken sick leave during the 48 weeks of treatment, and if so, how many days.

Outcome measures

Measure	Etanercept / ETN n=59 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=25 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Number of Patients With Sick Leave During 48 Weeks Treatment Patients employed during the study	45 patients	13 patients
Number of Patients With Sick Leave During 48 Weeks Treatment Patients with sick leave during the past 12 months	23 patients	10 patients

SECONDARY outcome

Timeframe: 48 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

Patients were asked whether or not they had taken sick leave during the 48 weeks of treatment, and if so, how many days. The mean number of days is based on those patients who had sick leave during the treatment period.

Outcome measures

Measure	Etanercept / ETN n=59 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=25 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Number of Sick Days Per Patient During the 48 Weeks of Treatment	37.67 Sick days per patient Interval 0.5 to 232.0	40.05 Sick days per patient Interval 2.0 to 252.0

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment

Patient Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity. The 0881A3-402 (NCT00247962) baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=52 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=24 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Patient Global Assessment of Disease Activity From Baseline to Week 38	46.23 units on scale Standard Deviation 24.24	36.08 units on scale Standard Deviation 36.09

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

Total Back Pain was measured on a 0 to 100 mm VAS, with 0 mm indicating no pain. The 0881A3-402 (NCT00247962) baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=52 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=24 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Total Back Pain Score From Baseline to Week 38	41.06 units on scale Standard Deviation 28.52	34.17 units on scale Standard Deviation 31.40

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

BASFI is a validated self assessment tool that determines the degree of functional limitation in Ankylosing Spodylitis (AS) patients. Utilizing a VAS of 0-10 (0=easy, 10=impossible), patients answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions, with a maximum score of 100 mm. The 0881A3-402 (NCT00247962) baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=52 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=24 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Bath Ankylosing Spondylitis Functional Index (BASFI) Score From Baseline to Week 38	32.95 units on scale Standard Deviation 20.81	23.41 units on scale Standard Deviation 21.14

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who received at least 1 dose of study drug and had at least 1 post-baseline assessment.

BASDAI is a validated self assessment tool used to determine disease activity in patients with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The final BASDAI score averages the individual assessments for a final score range of 0-10. The 0881A3-402 (NCT00247962) baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=52 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=24 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score From Baseline to Week 38	46.00 units on scale Standard Deviation 31.45	31.13 units on scale Standard Deviation 43.76

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. The 0881A3-402 (NCT00247962) baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=57 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=24 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Bath Ankylosing Spondylitis Metrology Index (BASMI) Score From Baseline to Weeks 38	1.21 units on scale Standard Deviation 1.40	0.83 units on scale Standard Deviation 1.31

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug and had at least 1 post-baseline assessment.

BASDAI is a validated self assessment tool used to determine disease activity in patients with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The fatigue-specific score is presented here. The 0881A3-402 (NCT00247962) baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=52 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=24 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score for Fatigue From Baseline to Week 38	40.46 units on scale Standard Deviation 25.53	29.88 units on scale Standard Deviation 34.33

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug, had at least 1 post-baseline assessment, and completed 38 weeks.

ASQoL is a questionnaire that assesses disease-specific quality of life (QoL). It consists of 18 statements that are relevant to the physical and mental conditions for a patient with Ankylosing Spondylitis (AS): mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the patient as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). The 0881A3-402 baseline score was used as the baseline for this analysis. Change = baseline - week 38.

Outcome measures

Measure	Etanercept / ETN n=28 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=15 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change in Baseline Ankylosing Spondylitis Quality of Life (ASQoL) Score From Baseline to Week 38	7.64 units on scale Standard Deviation 5.88	4.40 units on scale Standard Deviation 6.19

SECONDARY outcome

Timeframe: Baseline and 38 weeks

Population: All patients from United Kingdom sites who completed study 0881A3-402 (NCT00247962), continued into this study, received at least 1 dose of study drug had at least 1 post-baseline assessment and completed 38 weeks.

Haywood quality of life instrument was utilized in the United Kingdom as the ASQoL measure. The ASQoL is an AS-specific measure of QoL, scores range from 0 (good QoL) to 80 (poor QoL). ASQoL is intended to measure the quality of life by means of questions about mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Patient's 0881A3-402 baseline score was used in the analysis. Change=baseline-week 38.

Outcome measures

Measure	Etanercept / ETN n=27 Participants Patients received ETN dose 50 mg once weekly in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.	SSZ / ETN n=14 Participants Patients received Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into study 405, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Change From Baseline Haywood Quality of Life Score From Baseline to Week 38	25.98 units on scale Standard Deviation 16.51	16.14 units on scale Standard Deviation 19.25

Adverse Events

Etanercept

Serious events: 5 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Measure	Etanercept n=84 participants at risk Patients received ETN dose 50 mg once weekly or Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into this study, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
Hepatobiliary disorders Liver function test abnormal	1.2% 1/84
Gastrointestinal disorders Abdominal pain	1.2% 1/84
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	1.2% 1/84
Gastrointestinal disorders Ileitis	1.2% 1/84
Musculoskeletal and connective tissue disorders Spinal fracture	1.2% 1/84

Other adverse events

Measure	Etanercept n=84 participants at risk Patients received ETN dose 50 mg once weekly or Sulphasalazine dose 3 g daily in study 0881A3-402 for 16 weeks. Upon enrollment into this study, all received subcutaneous injections of etanercept 50 mg once weekly for 36 weeks.
General disorders Accidental injury	7.1% 6/84
General disorders Flu syndrom	6.0% 5/84
General disorders Headache	7.1% 6/84
General disorders Infection	11.9% 10/84
General disorders Injection site reaction	6.0% 5/84
General disorders Pain	6.0% 5/84
Gastrointestinal disorders Digestive system general	14.3% 12/84
Blood and lymphatic system disorders Hemic and lymphatic system general	8.3% 7/84
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 5/84
Musculoskeletal and connective tissue disorders Arthritis	8.3% 7/84
Nervous system disorders Nervous system general	9.5% 8/84
Respiratory, thoracic and mediastinal disorders Pharyngitis	7.1% 6/84
Respiratory, thoracic and mediastinal disorders Upper respiratory system general	27.4% 23/84
Skin and subcutaneous tissue disorders Skin and appendages general	7.1% 6/84
Eye disorders Iritis	6.0% 5/84

Additional Information

U. S. Contact Center

Wyeth

Email: clintrialresults@wyeth.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER