Trial Outcomes & Findings for Intestinal Inflammation in Ankylosing Spondylitis and the Effects of Adalimumab on Mucosal Healing (NCT NCT01174186)

Results Overview

Lewis' score describes the amount of inflammation seen optically by capsular endoscopy. Gralnek et al. devised and validated the Lewis score index, based on three endoscopic parameters: villous edema, ulcer and stenosis/stricture. Using these parameters, the authors established a score range of 8-4,800 points where: LS \< 135 reflects normal mucosal appearances, LS 135-790 mild mucosal inflammatory change and an LS value ≥790 moderate to severe mucosal inflammatory changes. The patients had endoscopy performed at baseline and again after 20 weeks. The number of patients improving was compared to number of patients deteriorating

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

30 participants

Primary outcome timeframe

20 weeks

Results posted on

2014-12-02

Participant Flow

SpA patients eligible for anti-TNF treatment as described by ASAS guidelines were included from outpatient clinics in Northern Jutland, Denmark. Patients were included over a 2 years and three months time span

Patient on current non-steroidal anti-inflammatory (NSAID) treatment were subjected to a 4 week long wash-out period, because NSAID can cause falsely elevated fecal calprotectin levels

Participant milestones

Participant milestones
Measure	Calprotetin Elevated Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given	Calprotectin Normal Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week
Overall Study STARTED	15	15
Overall Study COMPLETED	15	12
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Calprotetin Elevated Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given	Calprotectin Normal Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Intestinal Inflammation in Ankylosing Spondylitis and the Effects of Adalimumab on Mucosal Healing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Calprotetin Elevated n=15 Participants Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given	Calprotectin Normal n=15 Participants Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment Denmark	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
Bath Ankylosing Spondylitis Disease Activity Index >4	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
No effect of NSAID	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
Expert opinion of active disease	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 20 weeks

Population: Because endoscopy has a small risk for perforation. The study was designed so only patients with active inflammation at baseline had follow-up endoscopy performed. Because all patients with normal calprotectin levels had normal endoscopy, follow-up was only performed on this group of patients.

Lewis' score describes the amount of inflammation seen optically by capsular endoscopy. Gralnek et al. devised and validated the Lewis score index, based on three endoscopic parameters: villous edema, ulcer and stenosis/stricture. Using these parameters, the authors established a score range of 8-4,800 points where: LS \< 135 reflects normal mucosal appearances, LS 135-790 mild mucosal inflammatory change and an LS value ≥790 moderate to severe mucosal inflammatory changes. The patients had endoscopy performed at baseline and again after 20 weeks. The number of patients improving was compared to number of patients deteriorating

Outcome measures

Outcome measures
Measure	Calprotetin Elevated n=15 Participants Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given	Calprotectin Normal Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week
Change Lewis Score Index	-225 units on a scale Interval -493.0 to -112.0	—

PRIMARY outcome

Timeframe: Baseline to 52 weeks

Population: 15 patients in each group was included. 3 in the calprotectin negative group patients did not fulfill the entire study period (1 lost to follow-up, 2 withdrew consent). Data analysed as last observation carried forward.

Feacal calprotectin is a protein and a marker of the degree of inflammation in the intestine, but not the site of inflammation. We measured the level calprotectin continuously in each of the patients. Difference was inferred by repeated measurement ANOVA

Outcome measures

Outcome measures
Measure	Calprotetin Elevated n=15 Participants Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given	Calprotectin Normal n=15 Participants Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week
Change in Intestinal Inflammation Measured by Faecal Calprotectin	44 mg/g Interval 30.0 to 147.0	30 mg/g Interval 30.0 to 30.0

SECONDARY outcome

Timeframe: one year

Inflammation on MRI assessed by the Spondyloarthritis Consortium of Canada score and a Danish scoring method

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: one year

clinical measurements of inflammation in spondyloarthritis patients as described by the Assessment Group in Ankylosing Spondylitis (ASAS)

Outcome measures

Outcome data not reported

Adverse Events

Calprotetin Elevated

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Calprotectin Normal

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Calprotetin Elevated n=15 participants at risk Spondylitis patients with active inflammation and elevated calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week except the first time where 80 mg is given	Calprotectin Normal n=15 participants at risk Spondylitis patients with active inflammation and normal calprotectin Adalimumab: Tumor Necrosis Factor (TNF) alpha inhibitor given 40 mg subcutaneously every other week
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Number of events 1 • Adverse events were collected during the entire follow-up period of one year	0.00% 0/15 • Adverse events were collected during the entire follow-up period of one year
Gastrointestinal disorders Gastro intestinal bleeding	6.7% 1/15 • Number of events 1 • Adverse events were collected during the entire follow-up period of one year	0.00% 0/15 • Adverse events were collected during the entire follow-up period of one year

Other adverse events

Adverse event data not reported

Additional Information

René Oestgaard

Silkeborg Regional Hospital

Phone: 0045 78 41 50 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place