Trial Outcomes & Findings for Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH) (NCT NCT01086540)

Twenty-six study sites in the US were activated. Of these, 19 sites screened a total of 108 participants. Fifty-seven participants were randomized and study results summarized.

Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH)

The six minute walk test measures the distance a participant is able to walk over a total of six minutes on a hard, flat surface. The goal is for the participant to walk as far as possible in six minutes. The participant is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. The total distance walked, in meters, was recorded for each participant. Longer distances indicate better outcomes.

During a right heart catheterization, a catheter is guided to the right side of the heart and then into the pulmonary artery; blood flow through the heart is observed and is used to measure pressures in a participant's heart and lungs. The calculation of Pulmonary Vascular Resistance (PVR) is measured in Woods Units. Change is derived by measuring the difference between Baseline and Week 24 PVR (Week 24 minus Baseline). Higher PVR values indicate worse disease status.

The six minute walk test measures the distance a participant is able to walk over a total of six minutes on a hard, flat surface. The goal is for the participant to walk as far as possible in six minutes. The participant is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. The total distance walked, in meters, was recorded for each participant. Longer distances indicate better outcomes.

Assessment of time to clinical worsening, censored at Week 48, defined as the first occurrence of any of the following: * death, * hospitalization for Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH), * lung transplantation, * atrial septostomy, * addition of other Pulmonary Arterial Hypertension (PAH) therapeutic agents, or * worsening of the six minute walk distance by \> 20% and an increase in New York Heart Association functional class. Time to clinical worsening was defined as the first date that met any of the above criteria and was calculated in study days as: date of first event minus (-) date of treatment randomization. If a participant did not experience any of the referenced events by Week 48 or, if the date of death was after the 48 week follow-up period, time to clinical worsening was equal to the participant's duration of follow-up in the study.

Per protocol, from the time of study entry, participants were to remain on background PAH medical therapy with either a single agent or a combination of prostanoid, endothelin receptor antagonist, PDE-5 inhibitor, and/or guanylate cyclase stimulators as per the entry criteria. Doses should have remained stable through the Week 24 primary outcome/endpoint visit. If a dose of a background PAH medication was changed or a new PAH medication was added during the course of the trial, the date of the first dose change or additional medication was recorded. Time to the addition or modification of PAH medications was defined in study days as: date of the first time a PAH medication was modified or added minus (-) date of randomization.

The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. The SF-36 Mental Health component summary score is comprised of the Vitality Scale, the Social Functioning Scale, the Role-Emotional Scale, and the Mental Health Scale. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 is equivalent to no disability. A negative value indicates a decrease in quality of life from Baseline.

The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. The SF-36 Physical component summary score is comprised of the Physical Functioning Scale, the Role-Physical Scale, the Bodily Pain Scale, and the General Health Scale. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 is equivalent to no disability. A negative value indicates a decrease in quality of life from Baseline.

The HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities) and addresses scleroderma related manifestations that contribute to disability. The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome.

The total number of digital ulcers present on the dorsal and palmar surfaces for both the left and right fingers were captured at the Baseline study visit. The number of new digital ulcers since the last study visit (including any ulcers that had appeared and healed since the last study visit) on the dorsal and palmar surfaces for both the left and right fingers were captured at the post-Baseline study visits. The total number of digital ulcers on both hands was summed from the number present on the dorsal and palmar surfaces for both the left and right fingers.

Severity of Raynaud's phenomenon was measured by a Visual Analog Scale (VAS) of the Scleroderma Health Assessment Questionnaire (SHAQ). The SHAQ VAS includes a question asking, "In the past week, how much has your Raynaud's Phenomenon interfered with your activities?" Participants were asked to place a mark on a 15 cm line, scaled from 0 (does not interfere) to 100 (very severe limitation), to describe the severity of their Raynaud's phenomenon in the past week. The distance from the left edge of the line to the vertical line placed by the participant was measured in centimeters; VAS scores were converted to a 0 to 100 scale.

Carbon Monoxide Diffusing Capacity (DLCO) is a measure of lung function. Predicted values for DLCO were computed according to the Global Lung Function Initiative (GLI) all-age reference values and corrected for hemoglobin. Lower DLCO values indicate worse disease activity. DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide)

Oxygen saturation is the amount of oxygen that is in your bloodstream and is measured as the percentage of blood hemoglobin that is carrying oxygen. Normal oxygen saturation levels are considered to be 95-100 percent; low oxygen saturation values indicate worse disease. Room air oxygen saturation by pulse oximetry and/or amount of supplemental oxygen used, if saturation \<90%, were recorded.

During a right heart catheterization, a catheter is guided to the right side of the heart and then into the pulmonary artery; blood flow through the heart is observed and is used to measure pressures in a participant's heart and lungs. Pulmonary vascular resistance (PVR) is measured in Woods Units. Higher PVR values indicate worse disease status. Change in PVR is determined by Baseline value minus (-) Week 24 value.

The number of Grade 3, 4, and 5 Adverse Events (AEs), which were defined as possibly, probably, or definitely related to rituximab or placebo infusion. This study graded the severity of adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Total number of Grade 3, 4, and 5 AEs. Ref: National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Number of adverse events classified as infections. Reference: National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Death occurring after randomization and ≤ Week 48, and possibly, probably, or definitely resulting from assigned study treatment.

Death from any cause occurring after randomization and ≤ Week 48.

Death from any cause occurring after randomization and ≤ Week 104.