Observe the Frequency of Extra-Axial Symptoms in Korean Ankylosing Spondylitis (AS) Patients

A Prospective, Mono-Country, Multi-Center Study to Observe the Frequency of Extra-Axial Symptoms in Korean Ankylosing Spondylitis Patients on Adalimumab Therapy

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02333383

Acronym

AS PMOS

Enrollment

201

Registered

2015-01-07

Start date

2014-12-31

Completion date

2017-08-08

Last updated

2019-01-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ankylosing Spondylitis

Keywords

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, EAMs, Adalimumab

Brief summary

This was a prospective mono-country, multi-center study of the frequency of extra-axial manifestations (EAMs) in Ankylosing Spondylitis (AS) participants treated with adalimumab in routine clinical practice.

Detailed description

A baseline assessment was performed prior to the first dose of adalimumab. Participants received 40 mg of adalimumab every other week for one year. Study visits were conducted at 12, 28, 36 and 52 weeks. All participants were to have one follow-up approximately 70 days after the last dose of adalimumab.

Interventions

DRUGAdalimumab

Adalimumab pre-filled syringe, administered by subcutaneous injection

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

19 Years to 100 Years

Healthy volunteers

Inclusion criteria

* Participant must be ≥19 years of age * Participant has been diagnosed with ankylosing spondylitis (AS) according to the 1984 modified New York criteria for at least 3 months * Participant has active disease defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4, despite treatment with at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) or with disease-modifying antirheumatic drugs (DMARDs) for more than 3 months based on Korea AS reimbursement guideline * Participant is eligible for adalimumab in daily rheumatologic practice * Participant must provide written authorization form to use personal and/or health data prior to the entry into the study

Exclusion criteria

* Female participants who are pregnant or breastfeeding * Participants who are contraindicated to any anti-tumor necrosis factor (TNF) agent * Participant is enrolled in other clinical trials

Design outcomes

Primary

Measure	Time frame	Description
Frequency of Extra-Axial Manifestations (EAMs) of Interest	Baseline	The baseline assessment was performed prior to the first dose of adalimumab. The presence of peripheral arthritis (arthritis affecting shoulders, elbows, wrists, hands, knees, ankles, feet), enthesitis (inflammation of the areas where ligaments or tendons insert into bone) and dactylitis (inflammation of finger and/or toe joints) was noted. Peripheral arthritis was defined as ≥1 swollen joint on the Swollen Joint Count scale (SJC; range, 0 to 44, excluding hip joints). Enthesitis was defined as at least one inflamed enthesis in the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES, 0 to 13, with higher scores representing more severe disease) or of the plantar fascia of the foot. Dactylitis was measured by a simple count of dactylitic digits.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Participants With Enthesitis at Baseline	Baseline, Week 12, Week 28, Week 36, Week 52	Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Each domain was graded for the presence (1) or absence (0) of tenderness yielding total MASES ranging from 0 (0 sites with tenderness) to 13 (worst possible score; 13 sites with tenderness). Negative values indicate improvement from baseline.
Proportion of Participants With Enthesitis of the Plantar Fascia	Baseline, Week 12, Week 28, Week 36, Week 52	The plantar fascia is a ligament that runs along the bottom of each foot. The percentage of participants who had enthesitis of the plantar fascia was documented at each study visit.
Proportion of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response	Baseline, Week 12, Week 28, Week 36, Week 52	The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale \[NRS\]) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity. BASDAI 50 is a 50% improvement from baseline in BASDAI score.
Mean Change in Tender Joint Counts (TJC) in Participants With Peripheral Arthritis (≥1 Swollen Joint) at Baseline	Baseline, Week 12, Week 28, Week 36, Week 52	Forty-six joints were assessed for tenderness by physical examination. Tenderness of each joint was classified as present (1) or absent (0), for a total possible TJC score of 0 (0 joints with tenderness) to 46 (worst possible score/46 joints with tenderness). Negative values indicate improvement from baseline.
Mean Change in Change in Swollen Joint Counts (SJC) in Participants With Peripheral Arthritis (≥1 Swollen Joint) at Baseline	Baseline, Week 12, Week 28, Week 36, Week 52	Forty-four joints, excluding hip joints, were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score SJC of 0 (0 joints with swelling) to 44 (worst possible score/44 joints with swelling). Negative values indicate improvement from baseline.
Mean Change in Dactylitis Score in Participants With Dactylitis at Baseline	Baseline, Week 12, Week 28, Week 36, Week 52	Assessment of the presence or absence of dactylitis (inflammation of finger and/or toe joints) as well as grading of tenderness and swelling in all 20 of the participants' digits was performed. Tenderness at each site was quantified from absent to severe. Swelling was quantified from mild to severe. Total Dactylitis Assessment scores ranged from 0 (no digits with dactylitis) to 20 (worst possible score; 20 digits with dactylitis). Negative values indicate improvement from baseline.

Participant flow

Pre-assignment details

Intention-to-Treat (ITT) population: Participants who received at least one dose of adalimumab and had extra-axial manifestations (EAMs) assessed at baseline

Participants by arm

Arm	Count
Participants With Ankylosing Spondylitis Adalimumab 40 mg every other week by subcutaneous (SC) injection for 52 weeks	201
Total	201

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adalimumab discontinuation	21
Overall Study	Lost to Follow-up	15
Overall Study	Transfer to another hospital	2
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Participants With Ankylosing Spondylitis
Age, Continuous	39.84 years STANDARD_DEVIATION 12.34
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	201 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Sex: Female, Male Female	39 Participants
Sex: Female, Male Male	162 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 201
other Total, other adverse events	18 / 201
serious Total, serious adverse events	8 / 201

Outcome results

Primary

Frequency of Extra-Axial Manifestations (EAMs) of Interest

The baseline assessment was performed prior to the first dose of adalimumab. The presence of peripheral arthritis (arthritis affecting shoulders, elbows, wrists, hands, knees, ankles, feet), enthesitis (inflammation of the areas where ligaments or tendons insert into bone) and dactylitis (inflammation of finger and/or toe joints) was noted. Peripheral arthritis was defined as ≥1 swollen joint on the Swollen Joint Count scale (SJC; range, 0 to 44, excluding hip joints). Enthesitis was defined as at least one inflamed enthesis in the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES, 0 to 13, with higher scores representing more severe disease) or of the plantar fascia of the foot. Dactylitis was measured by a simple count of dactylitic digits.

Time frame: Baseline

Population: Intention-to-Treat (ITT) population: Participants who received at least one dose of adalimumab and had extra-axial manifestations (EAMs) assessed at baseline

Arm	Measure	Group	Value (NUMBER)
Participants With Ankylosing Spondylitis	Frequency of Extra-Axial Manifestations (EAMs) of Interest	Enthesitis	46.27 Percentage of participants
Participants With Ankylosing Spondylitis	Frequency of Extra-Axial Manifestations (EAMs) of Interest	Peripheral arthritis	33.33 Percentage of participants
Participants With Ankylosing Spondylitis	Frequency of Extra-Axial Manifestations (EAMs) of Interest	Dactylitis	2.99 Percentage of participants

Secondary

Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Participants With Enthesitis at Baseline

Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Each domain was graded for the presence (1) or absence (0) of tenderness yielding total MASES ranging from 0 (0 sites with tenderness) to 13 (worst possible score; 13 sites with tenderness). Negative values indicate improvement from baseline.