Trial Outcomes & Findings for Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis (NCT NCT05125679)

NCT ID: NCT05125679

Last Updated: 2025-03-30

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 15 participants
• Primary outcome timeframe: Baseline (Week 0) and Week 32
• Results posted on: 2025-03-30

Participant Flow

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.

Participant milestones

Measure	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.	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.
Overall Study STARTED	7	8
Overall Study Participants With Intermediate Cardiovascular Risk (ICR)	3	5
Overall Study COMPLETED	5	3
Overall Study NOT COMPLETED	2	5

Reasons for withdrawal

Measure	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.	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.
Overall Study Study Terminated by Sponsor	2	5

Baseline Characteristics

Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to Severe Plaque Psoriasis

Baseline characteristics by cohort

Measure	Guselkumab 100 mg: Non-Nicotine Users n=8 Participants 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.	Total n=15 Participants Total of all reporting groups	Guselkumab 100 mg: Nicotine Users n=7 Participants 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.
Age, Continuous	39.1 years STANDARD_DEVIATION 12.8 • n=4 Participants	44.1 years STANDARD_DEVIATION 14.06 • n=27 Participants	49.9 years STANDARD_DEVIATION 14.09 • n=93 Participants
Age, Customized Children (2-11 years)	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Age, Customized Adolescents (12-17 years)	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Age, Customized Adults (18-64 years)	8 Participants n=4 Participants	14 Participants n=27 Participants	6 Participants n=93 Participants
Age, Customized From 65 to 84 years	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=93 Participants
Age, Customized 85 years and over	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Sex: Female, Male Female	5 Participants n=4 Participants	5 Participants n=27 Participants	0 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=4 Participants	10 Participants n=27 Participants	7 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=4 Participants	13 Participants n=27 Participants	6 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Race (NIH/OMB) White	8 Participants n=4 Participants	13 Participants n=27 Participants	5 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=93 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=3 Participants 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.
Change From Baseline in Coronary Flow Reserve (CFR) at Week 32	-0.080 ratio Standard Deviation 0.2773	0.173 ratio Standard Deviation 0.6478

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=2 Participants 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.
Change From Baseline in CFR at Week 16	0.113 ratio Standard Deviation 0.3099	0.435 ratio Standard Deviation 0.2899

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=2 Participants 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.
Change From Baseline in Absolute Global Longitudinal Strain (GLS) at Week 16	-1.377 percentage of myocardial shortening Standard Deviation 0.9660	-2.625 percentage of myocardial shortening Standard Deviation 0.9829

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=3 Participants 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.
Change From Baseline in Absolute GLS at Week 32	0.850 percentage of myocardial shortening Standard Deviation 0.6065	-3.063 percentage of myocardial shortening Standard Deviation 3.0593

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=2 Participants 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.
Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 16	0.77 meter per second (m/s) Standard Deviation 0.503	-0.35 meter per second (m/s) Standard Deviation 0.495

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=2 Participants 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.
Change From Baseline in cfPWV at Week 32	1.37 meter per second (m/s) Standard Deviation 1.332	-1.00 meter per second (m/s) Standard Deviation 0.283

SECONDARY outcome

Timeframe: 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'.

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

Outcome measures

Measure	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.	Guselkumab 100 mg: Non-Nicotine Users n=2 Participants 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.
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 outcome

Timeframe: 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'.

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

Outcome measures

Measure	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.	Guselkumab 100 mg: Non-Nicotine Users n=3 Participants 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.
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 outcome

Timeframe: 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'.

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

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	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.
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 outcome

Timeframe: 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'.

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

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=3 Participants 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.	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.
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 outcome

Timeframe: 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.

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

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=5 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=5 Participants 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.
Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 16	0.024 ratio Standard Deviation 0.6124	0.132 ratio Standard Deviation 0.7874

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=6 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=6 Participants 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.
Change From Baseline in CFR Among Nicotine Users and Non-nicotine Users at Weeks 32	0.487 ratio Standard Deviation 1.1418	-0.253 ratio Standard Deviation 0.7173

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=5 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=4 Participants 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.
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	-0.780 percentage of myocardial shortening Standard Deviation 2.3553

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=6 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=5 Participants 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.
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	-2.490 percentage of myocardial shortening Standard Deviation 2.3020

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=5 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=4 Participants 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.
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	-0.38 meter per second (m/s) Standard Deviation 0.330

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=5 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=5 Participants 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.
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	-0.80 meter per second (m/s) Standard Deviation 0.791

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Guselkumab 100 mg: Nicotine Users n=7 Participants 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.	Guselkumab 100 mg: Non-Nicotine Users n=8 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	1 Participants	2 Participants

Adverse Events

Guselkumab 100 mg: Nicotine Users

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Guselkumab 100 mg: Non-Nicotine Users

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Guselkumab 100 mg: Nicotine Users n=7 participants at risk 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.	Guselkumab 100 mg: Non-Nicotine Users n=8 participants at risk 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.
Injury, poisoning and procedural complications Ligament Rupture	0.00% 0/7 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.	12.5% 1/8 • Number of events 1 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.

Other adverse events

Measure	Guselkumab 100 mg: Nicotine Users n=7 participants at risk 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.	Guselkumab 100 mg: Non-Nicotine Users n=8 participants at risk 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.
Cardiac disorders Atrial Fibrillation	0.00% 0/7 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.	12.5% 1/8 • Number of events 1 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.
Injury, poisoning and procedural complications Ligament Rupture	0.00% 0/7 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.	12.5% 1/8 • Number of events 1 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Number of events 1 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.	0.00% 0/8 • Week 0 up to 12 weeks post last dose of study drug (up to Week 40) The safety analysis set included all participants who received at least 1 dose of guselkumab.

Additional Information

Senior EMEA Medical Advisor Immunology

Janssen-Cilag Limited

Phone: 844-434-4210

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the Sponsor for review at least 60 days before submission for publication or presentation. If requested by the Sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
• Publication restrictions are in place

Restriction type: OTHER