Psoriasis
Conditions
Brief summary
The purpose of this study is to evaluate the effect of guselkumab on coronary flow reserve (CFR), measured by transthoracic doppler-echocardiography, in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.
Detailed description
Psoriasis is a common chronic inflammatory disease that affects 2 percent (%)-3% of the population and has an impact on physical and emotional health-related quality-of-life that is comparable to major illnesses such as cancer, heart disease and depression. Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that binds to the p19 protein subunit of human interleukin 23 (IL-23) with high specificity and affinity. Binding of guselkumab to the IL-23 p19 subunit blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling and subsequent cytokine production. Guselkumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy. This study aims to investigate the efficacy of guselkumab in reducing surrogate parameters of vascular dysfunction and cardiovascular risk. This study will consist of two Screening Visits (Screening Visit S1 at a maximum of 2 weeks prior to Screening Visit S2, to occur at a minimum of 2 weeks and maximum of 4 weeks prior to Week 0), a Treatment Phase (up to 28 weeks), Final Efficacy Visit 4 weeks later (Week 32), and Final Safety Visit (Week 40). The efficacy assessments will be done locally at the sites and safety will be monitored by assessment of adverse events, clinical laboratory tests, physical examinations, vital signs, and concomitant medication review. The total duration of the study will be 40 weeks.
Interventions
DRUGGuselkumab
Guselkumab will be administered by subcutaneous injection.
Sponsors
Janssen-Cilag Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant has a diagnosis of moderate-to-severe plaque psoriasis (with or without psoriatic arthritis \[PsA\]) for at least 6 months prior to the first dose of guselkumab at Week 0. Moderate-to-severe plaque psoriasis is defined as having a psoriasis area and severity index (PASI) score greater than or equal to (\>=) 12, investigator global assessment (IGA) score \>= 3 and involved body surface area (BSA) \>= 10 percent (%) at Screening Visit S1 * The participant has intermediate cardiovascular risk defined as having a coronary flow reserve (CFR) score \>= 2 to less than or equal to (\<=) 3.5 (criterion to be assessed by cardiologist at Screening Visit S2 and Week 0) * A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) at Screening Visit S1 * Within 2 months before the first administration of guselkumab, the participant has a negative QuantiFERON-TB Gold test result, or has a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated before the first administration of guselkumab * The participant has a chest radiograph (posterior-anterior view), taken within 3 months before the first administration of study agent and read by a qualified radiologist, with no evidence of current, active tuberculosis (TB) or old, inactive TB
Exclusion criteria
* The participant has a predominantly non-plaque form of psoriasis (example, erythrodermic, guttate, or pustular) * The participant has uncontrolled hypertension that needs immediate medical attention (criterion to be assessed by the dermatologist at Screening Visit S1 and by the cardiologist at Screening Phase 2) * The participant has taken any prohibited therapies before the planned first dose of guselkumab * A female participant is pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 5 months after the last dose of guselkumab * The participant has any clinically significant evidence of cardiac functional or valvular abnormalities, other than intermediate cardiovascular risk defined by CFR score \>=2 and \<=3.5, observed during the CFR assessment (criterion to be assessed by the dermatologist at Screening Visit S1, and to be confirmed by the cardiologist at Screening Visit S2) * The participant has any contraindications to adenosine infusion, or other contraindications listed in the summary of product characteristics (SmPC) (criterion to be assessed by the dermatologist at Screening Visit S1 and confirmed by the cardiologist at Screening Visit S2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Coronary Flow Reserve (CFR) at Week 32 | Baseline (Week 0) and Week 32 | Change from baseline in CFR at Week 32 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 micrograms per kilogram per minute (mcg/kg/min; coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16 | Baseline (Week 0) and Week 16 | Change from baseline in absolute GLS at Week 16 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values. |
| Change From Baseline in Absolute GLS at Week 32 | Baseline (Week 0) and Week 32 | Change from baseline in absolute GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values. |
| Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16 | Baseline (Week 0) and Week 16 | Change from baseline in cfPWV at Week 16 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV = distance (meters) / transit time (seconds). |
| Change From Baseline in cfPWV at Week 32 | Baseline (Week 0) and Week 32 | Change from baseline in cfPWV at Week 32 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV = distance (meters) / transit time (seconds). |
| Change From Baseline in CFR at Week 16 Among Participants With CFR >=2 to Less Than (<) 2.75 at Baseline | Baseline (Week 0) and Week 16 | Change from baseline in CFR at Week 16 among participants with CFR \>=2 to \<2.75 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest |
| Change From Baseline in CFR at Week 32 Among Participants With CFR >=2 to <2.75 at Baseline | Baseline (Week 0) and Week 32 | Change from baseline in CFR at Week 32 among participants with CFR \>=2 to \<2.75 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest |
| Change From Baseline in CFR at Week 16 Among Participants With CFR >=2.75 to <=3.5 at Baseline | Baseline (Week 0) and Week 16 | Change from baseline in CFR at Week 16 among participants with CFR \>=2.75 to \<=3.5 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest |
| Change From Baseline in CFR at Week 16 | Baseline (Week 0) and Week 16 | Change from baseline in CFR at Week 16 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest. |
| Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 16 | Baseline (Week 0) and Week 16 | Change from baseline in cfPWV among nicotine users and non-nicotine users at Week 16 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV= distance (meters)/ transit time (seconds). |
| Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16 | Baseline (Week 0) and Week 16 | Change from baseline in CFR among nicotine users and non-users at Week 16 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest |
| Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32 | Baseline (Week 0) and Week 32 | Change from baseline in CFR among nicotine users and non-nicotine users at Weeks 32 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest |
| Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 16 | Baseline (Week 0) and Week 16 | Change from baseline in absolute GLS among nicotine users and non-nicotine users at Week 16 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values. |
| Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 32 | Baseline (Week 0) and Week 32 | Change from baseline in absolute GLS among nicotine users and non-nicotine users at Week 32 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values. |
| Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 32 | Baseline (Week 0) and Week 32 | Change from baseline in cfPWV among nicotine users and non-nicotine users at Week 32 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV= distance (meters)/ transit time (seconds). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Week 0 up to 12 weeks post last dose of study drug (up to Week 40) | Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after initial administration study intervention (guselkumab) through the day of last dose within the study phase plus 12 weeks or the date of the Final Safety visit, whichever was the latest, was considered to be TEAE. |
| Change From Baseline in CFR at Week 32 Among Participants With CFR >=2.75 to <=3.5 at Baseline | Baseline (Week 0) and Week 32 | Change from baseline in CFR at Week 32 among participants with CFR \>=2.75 to \<=3.5 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest |
Countries
Germany, Greece, Italy
Participant flow
Recruitment details
A total of 15 adult participants diagnosed with moderate-to-severe plaque psoriasis (with or without psoriatic arthritis) for at least 6 months prior to the first dose of guselkumab at Week 0 (baseline) of the study entry were enrolled and treated with at least one dose of guselkumab.
Participants by arm
| Arm | Count |
|---|---|
| Guselkumab 100 mg: Nicotine Users Participants who were nicotine users (who had used tobacco products and/or nicotine products) received guselkumab 100 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, 12, 20, and 28. | 7 |
| Guselkumab 100 mg: Non-Nicotine Users Participants who were non-nicotine users (who had refrained from using tobacco/nicotine products for at least 3 months prior to screening visit 1 \[4 to 6 weeks prior to Week 0\]) received guselkumab 100 mg SC injection at Weeks 0, 4, 12, 20, and 28. | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Terminated by Sponsor | 2 | 5 |
Baseline characteristics
| Characteristic | Guselkumab 100 mg: Nicotine Users | Guselkumab 100 mg: Non-Nicotine Users | Total |
|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 14.09 | 39.1 years STANDARD_DEVIATION 12.8 | 44.1 years STANDARD_DEVIATION 14.06 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 6 Participants | 8 Participants | 14 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65 to 84 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 7 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 1 / 7 | 2 / 8 |
| serious Total, serious adverse events | 0 / 7 | 1 / 8 |
Outcome results
Primary
Change From Baseline in Coronary Flow Reserve (CFR) at Week 32
Change from baseline in CFR at Week 32 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 micrograms per kilogram per minute (mcg/kg/min; coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in Coronary Flow Reserve (CFR) at Week 32 | -0.080 ratio | Standard Deviation 0.2773 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in Coronary Flow Reserve (CFR) at Week 32 | 0.173 ratio | Standard Deviation 0.6478 |
Secondary
Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16
Change from baseline in absolute GLS at Week 16 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16 | -1.377 percentage of myocardial shortening | Standard Deviation 0.966 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16 | -2.625 percentage of myocardial shortening | Standard Deviation 0.9829 |
Secondary
Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 16
Change from baseline in absolute GLS among nicotine users and non-nicotine users at Week 16 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 16 | -1.496 percentage of myocardial shortening | Standard Deviation 0.8452 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 16 | -0.780 percentage of myocardial shortening | Standard Deviation 2.3553 |
Secondary
Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 32
Change from baseline in absolute GLS among nicotine users and non-nicotine users at Week 32 were reported. GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 32 | -0.060 percentage of myocardial shortening | Standard Deviation 2.2065 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in Absolute GLS Among Nicotine Users and Non-users at Week 32 | -2.490 percentage of myocardial shortening | Standard Deviation 2.302 |
Secondary
Change From Baseline in Absolute GLS at Week 32
Change from baseline in absolute GLS is a myocardial deformation analysis that predominantly reflects the function of sub-endocardial longitudinally oriented fibers, which are most prone to ischemic damage and wall stress. The GLS is calculated at systole and diastole. Speckle tracking echocardiography (STE) were employed for the detection of left-ventricular (LV) myocardial strain. GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in Absolute GLS at Week 32 | 0.850 percentage of myocardial shortening | Standard Deviation 0.6065 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in Absolute GLS at Week 32 | -3.063 percentage of myocardial shortening | Standard Deviation 3.0593 |
Secondary
Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16
Change from baseline in cfPWV at Week 16 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV = distance (meters) / transit time (seconds).
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16 | 0.77 meter per second (m/s) | Standard Deviation 0.503 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16 | -0.35 meter per second (m/s) | Standard Deviation 0.495 |
Secondary
Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 16
Change from baseline in cfPWV among nicotine users and non-nicotine users at Week 16 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV= distance (meters)/ transit time (seconds).
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 16 | 0.34 meter per second (m/s) | Standard Deviation 0.716 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 16 | -0.38 meter per second (m/s) | Standard Deviation 0.33 |
Secondary
Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 32
Change from baseline in cfPWV among nicotine users and non-nicotine users at Week 32 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV= distance (meters)/ transit time (seconds).
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 32 | 0.84 meter per second (m/s) | Standard Deviation 1.191 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in cfPWV Among Nicotine Users and Non-users at Week 32 | -0.80 meter per second (m/s) | Standard Deviation 0.791 |
Secondary
Change From Baseline in cfPWV at Week 32
Change from baseline in cfPWV at Week 32 were reported. cfPWV is a direct measurement, and the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. cfPWV was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. cfPWV was calculated as cfPWV = distance (meters) / transit time (seconds).
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in cfPWV at Week 32 | 1.37 meter per second (m/s) | Standard Deviation 1.332 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in cfPWV at Week 32 | -1.00 meter per second (m/s) | Standard Deviation 0.283 |
Secondary
Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16
Change from baseline in CFR among nicotine users and non-users at Week 16 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16 | 0.024 ratio | Standard Deviation 0.6124 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16 | 0.132 ratio | Standard Deviation 0.7874 |
Secondary
Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32
Change from baseline in CFR among nicotine users and non-nicotine users at Weeks 32 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32 | 0.487 ratio | Standard Deviation 1.1418 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32 | -0.253 ratio | Standard Deviation 0.7173 |
Secondary
Change From Baseline in CFR at Week 16
Change from baseline in CFR at Week 16 were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest.
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 and \<=3.5 at screening visit 2 (2 to 4 weeks prior to Week 0) and baseline (Week 0).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in CFR at Week 16 | 0.113 ratio | Standard Deviation 0.3099 |
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in CFR at Week 16 | 0.435 ratio | Standard Deviation 0.2899 |
Secondary
Change From Baseline in CFR at Week 16 Among Participants With CFR >=2.75 to <=3.5 at Baseline
Change from baseline in CFR at Week 16 among participants with CFR \>=2.75 to \<=3.5 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2.75 to \<=3.5 at baseline (Week 0). None of the non-nicotine users had the baseline CFR measurement of \>=2.75 to \<=3.5 and thus, no data was reported for arm 'Guselkumab 100 mg: Non-Nicotine Users'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in CFR at Week 16 Among Participants With CFR >=2.75 to <=3.5 at Baseline | 0.113 ratio | Standard Deviation 0.3099 |
Secondary
Change From Baseline in CFR at Week 16 Among Participants With CFR >=2 to Less Than (<) 2.75 at Baseline
Change from baseline in CFR at Week 16 among participants with CFR \>=2 to \<2.75 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest
Time frame: Baseline (Week 0) and Week 16
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 to \<2.75 at baseline (Week 0). None of the nicotine users had the baseline CFR measurement of \>=2 to \<2.75 and thus, no data was reported for arm 'Guselkumab 100 mg: Nicotine Users'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in CFR at Week 16 Among Participants With CFR >=2 to Less Than (<) 2.75 at Baseline | 0.435 ratio | Standard Deviation 0.2899 |
Secondary
Change From Baseline in CFR at Week 32 Among Participants With CFR >=2.75 to <=3.5 at Baseline
Change from baseline in CFR at Week 32 among participants with CFR \>=2.75 to \<=3.5 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2.75 to \<=3.5 at baseline (Week 0). None of the non-nicotine users had the baseline CFR measurement of \>=2.75 to \<=3.5 and thus, no data was reported for arm 'Guselkumab 100 mg: Non-Nicotine Users'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Change From Baseline in CFR at Week 32 Among Participants With CFR >=2.75 to <=3.5 at Baseline | -0.080 ratio | Standard Deviation 0.2773 |
Secondary
Change From Baseline in CFR at Week 32 Among Participants With CFR >=2 to <2.75 at Baseline
Change from baseline in CFR at Week 32 among participants with CFR \>=2 to \<2.75 at baseline were reported. CFR was described as ability of coronary blood flow to increase substantially when required by metabolic demands, which might be up to 4 to 5 times greater during normal exercise compared to resting, and even greater with administration of pharmacological agents. CFR was measured non-invasively using transthoracic doppler echocardiography. First, initial spectral Doppler signals in distal portion of left anterior descending artery (LAD) was recorded and then adenosine 140 mcg/kg/min (coronary vasodilator) was administered for 5 minutes. Doppler signals were recorded continuously during the period of adenosine infusion. Baseline (Week 0): last non-missing measurement prior to or on day of 1st dose of guselkumab. CFR is the ratio of blood flow at stress during maximal dilation of the coronary arteries to blood flow at rest
Time frame: Baseline (Week 0) and Week 32
Population: FAS included all participants who received at least 1 dose of guselkumab. Here, 'N' (number of participants analyzed) signifies number of treated participants evaluable for this outcome measure with ICR defined by CFR \>=2 to \<2.75 at baseline (Week 0). None of the nicotine users had the baseline CFR measurement of \>=2 to \<2.75 and thus, no data was reported for arm 'Guselkumab 100 mg: Nicotine Users'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab 100 mg: Non-Nicotine Users | Change From Baseline in CFR at Week 32 Among Participants With CFR >=2 to <2.75 at Baseline | 0.173 ratio | Standard Deviation 0.6478 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after initial administration study intervention (guselkumab) through the day of last dose within the study phase plus 12 weeks or the date of the Final Safety visit, whichever was the latest, was considered to be TEAE.
Time frame: Week 0 up to 12 weeks post last dose of study drug (up to Week 40)
Population: The safety analysis set included all participants who received at least 1 dose of guselkumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Guselkumab 100 mg: Nicotine Users | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Guselkumab 100 mg: Non-Nicotine Users | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |