An Observational Study of Infliximab Injection in Ankylosing Spondylitis, Rheumatoid Arthritis, Psoriatic Arthritis and Psoriasis Participants

Post Marketing Surveillance of Remicade in Ankylosing Spondylitis, Rheumatoid Arthritis, Psoriatic Arthritis and Psoriasis Patients

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00760669

Enrollment

1061

Registered

2008-09-26

Start date

2007-05-31

Completion date

2011-04-30

Last updated

2013-10-29

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

Conditions

Arthritis, Psoriatic, Arthritis, Rheumatoid, Psoriasis, Spondylitis, Ankylosing

Keywords

Spondylitis, Ankylosing, Arthritis, Rheumatoid, Psoriasis, Arthritis, Psoriatic, Infliximab, Remicade

Brief summary

The purpose of this observational study is to evaluate the safety and effectiveness of infliximab injection under actual conditions of use in participants, and to learn more about its adverse events.

Detailed description

This is an observational, prospective (study following participants forward in time) study to assess safety and efficacy of infliximab injection under post-marketing use and identify problems related to adverse events in participants with ankylosing spondylitis (chronic inflammatory condition affecting the axial joints), rheumatoid arthritis (chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures), psoriasis (scaly skin rash) and psoriatic arthritis (a type of inflammatory arthritis associated with psoriasis). Participants with rheumatoid arthritis will receive 6 doses of infliximab 3 milligram per kilogram (mg/kg) as an intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) at Week 0, 2, 6 and will be observed for 30 weeks; and those with ankylosing spondylitis, psoriasis and psoriatic arthritis will also receive 6 doses of injection and will be observed for 24 to 30 weeks. Efficacy will be evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Psoriasis Area and Severity Index (PASI), swollen joint counts and tender joint count. Participants' safety will be monitored throughout the study.

Interventions

DRUGMethotrexate; observational study

Participants with RA will receive methotrexate based on physician's clinical judgement.

DRUGInfliximab; observational study

This is an observational study. Participants with RA, AS and PA receiving induction intravenous infusions (a fluid or a medicine delivered into a vein by way of a needle) of infliximab will be observed. Participants with RA will receive infliximab 3 milligram per kilogram (mg/kg) as an intravenous infusion over a 2-hour period followed by additional 3 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks (maintenance) thereafter up to 30 weeks. Participants with AS and PA will receive 5 mg/kg infliximab as an intravenous infusion over 2-hour period followed by additional doses at 2 and 6 weeks up to 24-30 weeks and 30 weeks, respectively.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

* Participants with ankylosing spondylitis who did not show adequate response to general treatments and with increased serological indices related to severe axial symptoms and inflammation * Participants with rheumatoid arthritis who show insufficient response to disease modifying antirheumatic drug (DMARD) including methotrexate * Participants with serious, active and progressive disease not previously treated with methotrexate or other DMARD * Participant with moderate to serious plaque psoriasis who are unresponsive, contra indicant or intolerable to the systemic therapy including cyclosporine, methotrexate or Psoralen Ultra-Violet A (PUVA) * Participant with active, progressive, psoriatic arthritis who have shown insufficient response to DMARD treatment

Exclusion criteria

None

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events (AEs) Caused by Drug Misuse, Abuse and Drug Interaction	Baseline up to Week 30	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Drug abuse is defined as the use of the study drug for a non-therapeutic effect, misuse was defined as use of the study medication in a way that was not prescribed and drug interaction was defined as a chemical or physiological reaction that can occur when 2 different drugs are taken together.
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 30	Baseline and Week 30	The BASDAI is a validated self-assessment tool used to assess disease activity in participants with ankylosing spondylitis. It consists of 6 items measuring fatigue, spinal pain, joint pain, areas of localized tenderness, intensity of morning stiffness and duration of morning stiffness. First 5 items are scored on a 10 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm=none to 10 mm=severe; and sixth item is scored on VAS ranging from 0=0 hours to 10=2 or more hours. The total BASDAI score ranges from 0 (none) to 10 (very severe).To give each symptom equal weighting, the average of the 2 scores relating to morning stiffness was taken. The resulting 0 to 50 score is divided by 5 to give a final BASDAI score. BASDAI total score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).
Change From Baseline in Erythrocytic Sedimentation Rate (ESR) at Week 30	Baseline and Week 30	The ESR is a laboratory test that provides a non-specific measure of inflammation. It assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm per hour. A higher rate indicated inflammation.
Change From Baseline in C-Reactive Protein (CRP) at Week 30	Baseline and Week 30	The CRP is acute serum protein released from liver. It is associated with low hemoglobin or erythropoetic resistance. The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is less than 1 milligram per deciliter (mg/dl). A decrease in the level of CRP indicated reduction in inflammation and therefore improvement.
Change From Baseline in Number of Swollen Joints at Week 30	Baseline and Week 30	Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit and scored on a scale ranging from 0 to 2, where 0=no swelling, 1=swelling, but bony landmarks seen and 2=swelling but bone marks not seen.
Change From Baseline in Number of Tender Joints at Week 30	Baseline and Week 30	Number of tender joints was determined by examination of 28 joints and identifying when tenderness was present. The number of tender joints was recorded on the joint assessment form at each visit and scored on a scale ranging from 0 to 3, where 0=no pain, 1=mild, 2= moderate and 3=severe.
Change From Baseline in Participants With Psoriasis Area and Severity Index (PASI) at Week 30	Baseline and Week 30	The PASI is combined assessment of lesion severity and area affected into single score; range: 0=no disease to 72=maximal disease. Body is divided into 4 sections (head, arms, trunk and legs); each area is scored by itself and scores were combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity was estimated by clinical signs: erythema, thickness, and scaling; scale: 0 (none) to 4 (severe). Final PASI=sum of severity parameters for each section \* area score \* weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4).
Overall Efficacy Assessment	Baseline up to Week 30	The level of improvement in symptom before and after the administration of the drug was assessed as per Investigator's discretion and the overall efficacy was assessed based on this result. The level of improvement in disease was assessed in three steps: improved, unchanged and aggravated as per Investigator's discretion.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Week 30	An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Unexpected Adverse Events	Baseline up to Week 30	Unexpected adverse events include those not listed in the approved product information and not described as precautions or warnings.
Number of Participants With Adverse Drug Reactions	Baseline up to Week 30	Adverse drug reactions are defined as adverse events for which the Investigator had not described the causal relationship to trial medication as not related.

Participant flow

Participants by arm

Arm	Count
Participants Receiving Infliximab Participants with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PA) receiving induction intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) of infliximab at Week 0, 2, and 6 were observed. Dosage and infusion intervals of infliximab were employed in accordance to the summary of product characteristics: participants with RA received infliximab 3 milligram per kilogram (mg/kg) as an intravenous infusion over a 2-hour period followed by additional 3 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks (maintenance) thereafter up to 30 weeks along with methotrexate, participants with AS and PA received 5 mg/kg infliximab as an intravenous infusion over 2-hour period followed by additional doses at 2 and 6 weeks up to 24-30 weeks and 30 weeks, respectively.	1,055
Total	1,055

Arm

Count

Participants Receiving Infliximab

Participants with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PA) receiving induction intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) of infliximab at Week 0, 2, and 6 were observed. Dosage and infusion intervals of infliximab were employed in accordance to the summary of product characteristics: participants with RA received infliximab 3 milligram per kilogram (mg/kg) as an intravenous infusion over a 2-hour period followed by additional 3 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks (maintenance) thereafter up to 30 weeks along with methotrexate, participants with AS and PA received 5 mg/kg infliximab as an intravenous infusion over 2-hour period followed by additional doses at 2 and 6 weeks up to 24-30 weeks and 30 weeks, respectively.

1,055

Total

1,055

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Not assessed for overall improvement	18
Overall Study	Participants missing efficacy assessment	6
Overall Study	Participants with overlapping cases	1
Overall Study	Took drug before entering in contract	5

Baseline characteristics

Characteristic	Participants Receiving Infliximab
Age Continuous	39.32 years STANDARD_DEVIATION 13.84
Sex: Female, Male Female	363 Participants
Sex: Female, Male Male	692 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	95 / 1,055
serious Total, serious adverse events	12 / 1,055

Outcome results

Primary

Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 30

The BASDAI is a validated self-assessment tool used to assess disease activity in participants with ankylosing spondylitis. It consists of 6 items measuring fatigue, spinal pain, joint pain, areas of localized tenderness, intensity of morning stiffness and duration of morning stiffness. First 5 items are scored on a 10 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm=none to 10 mm=severe; and sixth item is scored on VAS ranging from 0=0 hours to 10=2 or more hours. The total BASDAI score ranges from 0 (none) to 10 (very severe).To give each symptom equal weighting, the average of the 2 scores relating to morning stiffness was taken. The resulting 0 to 50 score is divided by 5 to give a final BASDAI score. BASDAI total score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).