A Study of Guselkumab in Participants With Systemic Sclerosis

Change from baseline in mRSS at Week 52 was reported. The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the thickening of the skin using the mRSS through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.

The percentage of participants who experienced worsening of mRSS at Week 24 and Week 52 was reported. The worsening of mRSS was defined as an increase from baseline greater than or equal to (>=) 5 points and >=20 percent (%) in mRSS. The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the thickening of the skin using the mRSS through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.

ACR CRISS is a composite endpoint. Firstly, participants were evaluated on not-improved criterion: new onset of renal crisis, >=15% decline in forced vital capacity [FVC] percent predicted relative to baseline, new onset of pulmonary arterial hypertension, and new onset of left ventricular failure. If yes, these participants were assigned probability score of 0.0. For remaining participants, percentage was based on CRISS domains: mRSS, FVC percent predicted, physician's global assessment, patient's global assessment and Health Assessment Questionnaire Disability-Index (HAQ-DI). Algorithm determines predicted probability of improvement from baseline by incorporating change in mRSS, FVC percent predicted, physician and patient global assessments and HAQ-DI. Outcome was a continuous variable between 0.0 and 1.0 (0 to 100%). Higher score=greater probability of improvement. ACR CRISS score >=0.60 was considered improved, while predicted probability below 0.60 was considered not improved.

FVC was the total amount of air (in liters) exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying interstitial lung disease.

Change from baseline in the percent predicted FVC at Week 24 and Week 52 was reported. FVC was the total amount of air (in liters) exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying interstitial lung disease.

DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. DLCO is measured using the single breath method. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath.

Change from baseline in the percent predicted DLCO at Week 24 and Week 52 was reported. DLCO is a measurement of the ability of the lungs to transfer gases from the air to the blood. DLCO is measured using the single breath method. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath.

Digital ulcers were defined as a full thickness (>3 millimeters [mm] in maximal diameter) skin lesion with loss of epithelium including lesions covered by eschar (excluding pitting scars and hyperkeratotic lesions). Healing was defined by re-epithelialization with loss of pain and exudate. The digital ulcer assessments and counting were performed by the investigator designee.

HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during past week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each activity category consisted of 2-3 items. For each item, level of difficulty was scored from 0 to 3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Total HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs that occur at or after the initial administration of study intervention. All TEAEs including serious and non-serious events are reported in this outcome measure.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs that occurred at or after the initial administration of study intervention. All TEAEs including serious and non-serious events are reported in this outcome measure.

An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/ incapacity, or resulted in congenital anomaly/birth defect. TEAEs were defined as AEs that occur at or after the initial administration of study intervention.

An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/ incapacity, or resulted in congenital anomaly/birth defect. TEAEs were defined as AEs that occur at or after the initial administration of study intervention.

AESI were defined as any newly identified malignancy or case of active tuberculosis (TB) or interstitial lung disease (ILD) occurring after the first study intervention administration in study participants and was reported by the investigator to the sponsor or designee within 24 hours after being made aware of the event. AESIs for this study included drug-induced liver injuries, active TB, ILD, hypersensitivity reaction, opportunistic infection and adverse cardiovascular events.

AESI were defined as any newly identified malignancy or case of active tuberculosis (TB) or interstitial lung disease (ILD) occurring after the first study intervention administration in study participants and was reported by the investigator to the sponsor or designee within 24 hours after being made aware of the event. AESIs for this study included drug-induced liver injuries, active TB, ILD, hypersensitivity reaction, opportunistic infection and adverse cardiovascular events.

Serum concentration of guselkumab was reported. The lower limit of quantification (LLOQ) for guselkumab was 0.01 micrograms per milliliter (mcg/mL).

Serum concentration of guselkumab was reported. The LLOQ for guselkumab was 0.01 mcg/mL.

Number of participants with anti-guselkumab antibody were reported. Serum samples were assessed for anti-drug antibodies.

Number of participants with anti-guselkumab antibody were reported. Serum samples were assessed for anti-drug antibodies.