Crohn's Disease, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Brief summary
Specific Aim 1. To determine the transcriptome of peripheral blood mononuclear cells isolated monocytes and target tissues in IMIDs. Specific Aim 2. To analyze the change in gene expression profiles in patients with Crohn's disease, psoriatic and rheumatoid arthritis before and after infliximab therapy.
Detailed description
Our hypothesis is that hematopoietic stem cells are very sensitive to elevated levels of TNFa, which potentiates their differentiation into myeloid effector cells. During their migration from the bone marrow to the end organ, these cells express a unique set of genes that function to prime these cells to respond to critical differentiation signals. Elucidation of this transcriptome through microarray analysis will provide insight into novel drug targets and a formal understanding of the biochemical and molecular genetic events linking IMIDs. To test our hypothesis, will determine the transcriptome in peripheral blood mononuclear cells and isolated monocytes from 20 normal healthy donors, 10 patients with psoriatic arthritis, 10 patients with psoriasis, 10 patients with Crohn's disease and 10 patients with rheumatoid arthritis. The transcriptome will also be examined in inflamed intestinal tissue from patients with Crohn's disease, psoriatic skin and synovial tissue from patients with rheumatoid and psoriatic arthritis.
Interventions
DRUGInfliximab
Subjects will be on a stable dose of methotrexate 12.5 to 20 mg per week and will be started on infliximab 5 mg/kg.
Sponsors
Centocor, Inc.
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Rheumatoid Arthritis * 18 years of age or older * 3 years duration of disease or less * Must meet ACR criteria * 3 tender or swollen joints * Positive RF or anti-CCP antibodies or evidence of erosions on plain radiographs * CRP \> 1.5 * Non-responder to methotrexate, but on a stable dose of 12.5 to 20 mg/week * Only subjects scheduled to receive infliximab as part of their care are eligible to participate. Crohn's disease * 12 years of age or older * Clinical and endoscopic confirmation of disease * CDAI \> 220 or evidence of intestinal inflammation on endoscopy * Documented failure to conventional therapy. * Only subjects scheduled to receive infliximab as part of their care are eligible to participate. Psoriatic arthritis * 18 years of age or older * Must meet CASPAR® criteria for diagnosis * RF and anti-CCP negative * 3 tender or swollen joints * Non-responder to methotrexate, but on a stable dose of 12.5 to 20 mg/week * Only subjects scheduled to receive infliximab as part of their care are eligible to participate. Psoriasis * 18 years of age or older * Total BSA \> 5%
Exclusion criteria
* Candidates for whom the procedures would be medically contraindicated would be excluded. * Patients with any active infections (viral or bacterial) will not be considered for inclusion into the trial. * Patients with history of chronic infection such as hepatitis, pneumonia or chronic pyelonephritis; those with current signs or symptoms of severe or progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease including demyelinating disease such as multiple sclerosis. * Those with history of lymphoproliferative disease such as lymphoma or signs suggestive of lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, supraclavicular, epitrochlear, or periaortic areas), or splenomegaly will be excluded. * Patients with concomitant diagnosis of CHF, including medically controlled asymptomatic patients will not be eligible to participate. * Any current known malignancy or history of malignancy in the last 10 years will be excluded. History of basal cell carcinoma is not excluded. * Those with known bacterial, tuberculosis or opportunistic infections including but not limited to evidence of active cytomegalovirus , active Pneumocystis carinii, aspergillosis, or atypical mycobacterium infection within the previous 6 months will be ineligible. * Those with known infection with Human immunodeficiency virus (HIV) or known active hepatitis B or C (including associated active hepatitis) will be excluded. * Known substance abuse (drug or alcohol) within the previous 3 years. * Patients who have previously taken anti-TNF therapy are not eligible. * Patients who have been treated with DMARDS, biologic or investigational agents must wash out for at least 6 weeks prior to enrollment with the exception of those on methotrexate, who must be on a stable dose at least 2 weeks prior to start of study. * Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening. * Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening. * Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB. * Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline (Wk 0) Disease Activity Score (DAS28) | Baseline (Wk 0) | The DAS28 for RA and PsA subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The baseline DAS28 is an average of the study populations baseline disease activity score prior to the administration of Infliximab (remicade). A DAS28 score of higher than 5.1 is indicative of high disease activity, whereas a DAS28 below 3.2 indicates low disease activity. A subject is considered to be in remission if they have a DAS28 lower than 2.6. |
| Week 10 Disease Activity Score (DAS28) | Week 10 | The DAS28 for RA and PsA subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The week 10 DAS28 is an average of the study population's week 10 disease activity score after taking infliximab (remicade) for 10 weeks. A DAS28 score of higher than 5.1 is indicative of high disease activity, whereas a DAS28 below 3.2 indicates low disease activity. A subject is considered to be in remission if they have a DAS28 lower than 2.6. |
| Disease Activity Score (DAS28) Delta | Week 10 | The DAS28 Delta for RA and PsA subjects is measure used to determine the change in the severity of an individual's disease with positive delta indicating an improvement in the severity of subject's disease and a negative delta indicating a worsening of a subject's disease. The delta score is used to monitor treatment. The week 10 DAS28 Delta is determined by calculating the average change between the wk 0 and wk 10 DAS28. |
| Baseline (Wk 0) Psoriasis Area and Severity Index (PASI) | Baseline (Wk 0) | A PASI score for Ps subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The baseline PASI is an average of the study populations baseline disease activity score prior to the administration of infliximab (remicade). While higher PASI scores indicate more severe psoriasis, it is difficult for subjects or doctors to describe the clinical severity for any specific PASI number. |
| Baseline (Wk 10) Psoriasis Area and Severity Index (PASI) | Week 10 | A PASI score for Ps subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The week 10 PASI is an average of the study population's week 10 disease activity score after taking infliximab (remicade) for 10 weeks. |
| Psoriasis Area and Severity Index (PASI) Delta | Week 10 | The PASI Delta for Ps subjects is a measure used to determine the change in the severity of an individual's disease with a positive delta indicating an improvement in the severity of subject's disease and a negative delta indicating a worsening of a subject's disease. The delta score is used to monitor treatment. The week 10 PASI Delta is determined by calculating the average change between the wk 0 and wk 10 PASI. |
Countries
United States
Participant flow
Recruitment details
A total of 31 subjects were enrolled from our clinic between April 4th, 2007 and June 8th, 2009.
Pre-assignment details
Subjects were enrolled based on protocol inclusion / exclusion criteria. Subjects were required to be starting Infliximab as a requirement for entry into the study.
Participants by arm
| Arm | Count |
|---|---|
| Rheumatoid Arthritis (RA) RA subject starting Infliximab | 9 |
| Psoriatic Arthritis (PsA) PsA subjects starting Infliximab | 12 |
| Psoriasis (Ps) Ps subjects starting Infliximab | 10 |
| Total | 31 |
Baseline characteristics
| Characteristic | Rheumatoid Arthritis (RA) | Psoriatic Arthritis (PsA) | Psoriasis (Ps) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 9 Participants | 10 Participants | 27 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 11 | 53 years STANDARD_DEVIATION 13 | 41 years STANDARD_DEVIATION 15 | 48 years STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 6 Participants | 20 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 12 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 | 0 / 9 |
Outcome results
Primary
Baseline (Wk 0) Disease Activity Score (DAS28)
The DAS28 for RA and PsA subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The baseline DAS28 is an average of the study populations baseline disease activity score prior to the administration of Infliximab (remicade). A DAS28 score of higher than 5.1 is indicative of high disease activity, whereas a DAS28 below 3.2 indicates low disease activity. A subject is considered to be in remission if they have a DAS28 lower than 2.6.
Time frame: Baseline (Wk 0)
Population: Participant data analyzed per protocol using the following DAS28 formula \[(=0.56\*SQRT(Tender Joint Count)+0.28\*SQRT(Swollen Joint Count)+0.36\*LN(CRP(mg/L)+1)+0.014\*(Visual Analogue Scale+0.96 \]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psoriatic Arthritis (PsA) | Baseline (Wk 0) Disease Activity Score (DAS28) | 4.54 Score | Standard Deviation 1.24 |
| Rheumatoid Arthritis (RA) | Baseline (Wk 0) Disease Activity Score (DAS28) | 6.03 Score | Standard Deviation 1.16 |
Primary
Baseline (Wk 0) Psoriasis Area and Severity Index (PASI)
A PASI score for Ps subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The baseline PASI is an average of the study populations baseline disease activity score prior to the administration of infliximab (remicade). While higher PASI scores indicate more severe psoriasis, it is difficult for subjects or doctors to describe the clinical severity for any specific PASI number.
Time frame: Baseline (Wk 0)
Population: PASI formula PASI = 0.1 \* (erythemahead + indurationhead + desquamationhead) \* Area Scorehead + 0.2 \* (erythemaarm + indurationarm + desquamationarm) \* Area Scorearm + 0.3 \* (erythematorso + indurationtorso + desquamationtorso) \* Area Scoretorso + 0.4 \* (erythemaleg + indurationleg + desquamationleg) \* Area Scoreleg
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psoriatic Arthritis (PsA) | Baseline (Wk 0) Psoriasis Area and Severity Index (PASI) | 5.26 Index | Standard Deviation 1.82 |
Primary
Baseline (Wk 10) Psoriasis Area and Severity Index (PASI)
A PASI score for Ps subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The week 10 PASI is an average of the study population's week 10 disease activity score after taking infliximab (remicade) for 10 weeks.
Time frame: Week 10
Population: PASI formula PASI = 0.1 \* (erythemahead + indurationhead + desquamationhead) \* Area Scorehead + 0.2 \* (erythemaarm + indurationarm + desquamationarm) \* Area Scorearm + 0.3 \* (erythematorso + indurationtorso + desquamationtorso) \* Area Scoretorso + 0.4 \* (erythemaleg + indurationleg + desquamationleg) \* Area Scoreleg
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psoriatic Arthritis (PsA) | Baseline (Wk 10) Psoriasis Area and Severity Index (PASI) | 2.31 Index | Standard Deviation 5.85 |
Primary
Disease Activity Score (DAS28) Delta
The DAS28 Delta for RA and PsA subjects is measure used to determine the change in the severity of an individual's disease with positive delta indicating an improvement in the severity of subject's disease and a negative delta indicating a worsening of a subject's disease. The delta score is used to monitor treatment. The week 10 DAS28 Delta is determined by calculating the average change between the wk 0 and wk 10 DAS28.
Time frame: Week 10
Population: Participant data analyzed per protocol using the following DAS28 formula \[(=0.56\*SQRT(Tender Joint Count)+0.28\*SQRT(Swollen Joint Count)+0.36\*LN(CRP(mg/L)+1)+0.014\*(Visual Analogue Scale+0.96 \]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psoriatic Arthritis (PsA) | Disease Activity Score (DAS28) Delta | 1.21 Score Delta | Standard Deviation 0.6 |
| Rheumatoid Arthritis (RA) | Disease Activity Score (DAS28) Delta | 1.90 Score Delta | Standard Deviation 1.48 |
Primary
Psoriasis Area and Severity Index (PASI) Delta
The PASI Delta for Ps subjects is a measure used to determine the change in the severity of an individual's disease with a positive delta indicating an improvement in the severity of subject's disease and a negative delta indicating a worsening of a subject's disease. The delta score is used to monitor treatment. The week 10 PASI Delta is determined by calculating the average change between the wk 0 and wk 10 PASI.
Time frame: Week 10
Population: PASI formula PASI = 0.1 \* (erythemahead + indurationhead + desquamationhead) \* Area Scorehead + 0.2 \* (erythemaarm + indurationarm + desquamationarm) \* Area Scorearm + 0.3 \* (erythematorso + indurationtorso + desquamationtorso) \* Area Scoretorso + 0.4 \* (erythemaleg + indurationleg + desquamationleg) \* Area Scoreleg
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psoriatic Arthritis (PsA) | Psoriasis Area and Severity Index (PASI) Delta | 2.95 Index Delta | Standard Deviation 5.42 |
Primary
Week 10 Disease Activity Score (DAS28)
The DAS28 for RA and PsA subjects is an outcome measure used in determining the severity of an individual's disease. This score is used to assess disease activity and to make and monitor treatment decisions. The week 10 DAS28 is an average of the study population's week 10 disease activity score after taking infliximab (remicade) for 10 weeks. A DAS28 score of higher than 5.1 is indicative of high disease activity, whereas a DAS28 below 3.2 indicates low disease activity. A subject is considered to be in remission if they have a DAS28 lower than 2.6.
Time frame: Week 10
Population: Participant data analyzed per protocol using the following DAS28 formula \[(=0.56\*SQRT(Tender Joint Count)+0.28\*SQRT(Swollen Joint Count)+0.36\*LN(CRP(mg/L)+1)+0.014\*(Visual Analogue Scale+0.96 \]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psoriatic Arthritis (PsA) | Week 10 Disease Activity Score (DAS28) | 3.34 Score | Standard Deviation 1.06 |
| Rheumatoid Arthritis (RA) | Week 10 Disease Activity Score (DAS28) | 4.13 Score | Standard Deviation 1.28 |