Trial Outcomes & Findings for Rituximab in Rheumatoid Arthritis Lung Disease (NCT NCT00578565)

NCT ID: NCT00578565

Last Updated: 2012-10-01

Results Overview

DLco is one pulmonary function measure. For DLco, worsening was defined as decrease of at least 15% and improvement was defined as increase of at least 15%.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 10 participants
• Primary outcome timeframe: baseline, 48 weeks
• Results posted on: 2012-10-01

Participant Flow

Participants were recruited from Mayo Clinic and Brigham and Women's rheumatology outpatient clinics.

Participant milestones

Measure	Rituximab open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Overall Study STARTED	10
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Rituximab open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Overall Study Adverse Event	3

Baseline Characteristics

Rituximab in Rheumatoid Arthritis Lung Disease

Baseline characteristics by cohort

Measure	Rituximab n=10 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Age Continuous	64.7 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants
Duration of Rheumatoid Arthritis (RA)	13.8 Years n=5 Participants
Duration of Interstitial Lung Disease (ILD)	3.2 Years n=5 Participants
Histological subtypes of RA-ILD Nonspecific Interstitial Pneumonia (NSIP)	6 participants n=5 Participants
Histological subtypes of RA-ILD Usual Interstitial Pneumonia (UIP)	4 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 48 weeks

Population: Three participants of the 10 enrolled withdrew or died before the end of the study.

DLco is one pulmonary function measure. For DLco, worsening was defined as decrease of at least 15% and improvement was defined as increase of at least 15%.

Outcome measures

Measure	Rituximab n=7 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks Stable	4 participants
Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks Improved	2 participants
Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks Worsened	1 participants

PRIMARY outcome

Timeframe: baseline, 48 weeks

Population: Three participants of the 10 enrolled withdrew or died before the end of the study.

FVC is one measure of pulmonary function. For FVC, worsening was defined as decrease of at least 10% and improvement was defined as increase of at least 10%.

Outcome measures

Measure	Rituximab n=7 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks Stable	4 participants
Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks Improved	2 participants
Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks Worsened	1 participants

SECONDARY outcome

Timeframe: baseline, 48 weeks

Population: Three participants of the 10 enrolled withdrew or died before the end of the study.

Three serial HRCT scans of each patient were scored independently and simultaneously by two core radiologists, who were blinded to the sequence in which three scans were obtained (at screening, 24 and 48 weeks). The HRCT scoring sheet scored different domains of abnormality such as, linear opacities, consolidation, ground-glass density, etc. Radiographers reported composite impression based on scoring according to worsening, no worsening or improvement of relevant domains.

Outcome measures

Measure	Rituximab n=7 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks Stable	5 participants
Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks Improved	1 participants
Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks Worsened	1 participants

SECONDARY outcome

Timeframe: baseline, 48 weeks

Population: Three participants of the 10 enrolled withdrew or died before the end of the study.

The DAS28 score is a measure of RA disease activity calculated using variables such as swollen joint count, the Erythrocyte Sedimentation Rate (ESR) and patient reported assessment of health.

Using this data, the DAS28 calculation provides a number on a scale from 0-10 indicating the current activity of a patient's RA. A DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 score lower than 2.6.

Outcome measures

Measure	Rituximab n=7 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks Baseline	5.5 units on a scale Interval 2.2 to 7.3
Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks 48 Weeks	3.3 units on a scale Interval 2.5 to 4.4

SECONDARY outcome

Timeframe: baseline, 48 weeks

Population: Three participants of the 10 enrolled withdrew or died before the end of the study.

The DAS28 score is a measure of RA disease activity calculated using variables such as swollen joint count, the Erythrocyte Sedimentation Rate (ESR) and patient reported assessment of health.

Using this data, the DAS28 calculation provides a number on a scale from 0-10 indicating the current activity of a patient's RA. A DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 score lower than 2.6.

Outcome measures

Measure	Rituximab n=7 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score.	-31.8 percentage of change Interval -62.0 to 24.0

SECONDARY outcome

Timeframe: baseline, 48 weeks

Population: Three participants of the 10 enrolled withdrew or died before the end of the study.

The percentage change from baseline to week 48 in a participant's perception of the impact of health on his or her quality of life was collected on the Health Assessment Questionnaire (HAQ). The HAQ measures a person's ability to function with arthritis. The questionnaire is divided into 8 categories (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip and Activities) which include several questions for each category. The category score is determined by the highest score of the set of questions for each category. The disability score is determined by adding the scores for all categories and dividing by 8. The disability scale ranges from 0 (best - without any difficulty) to 3 (worst - unable to do much).

Outcome measures

Measure	Rituximab n=7 Participants open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks	85.9 percentage of change Interval -80.0 to 300.0

Adverse Events

Rituximab

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rituximab n=10 participants at risk open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Cardiac disorders Congestive Heart Failure	10.0% 1/10 • Number of events 1 • Participants were followed for adverse events during the entire study period, approximately 48 weeks.
Respiratory, thoracic and mediastinal disorders Pneumonia and Adult Respiratory Distress Syndrome	10.0% 1/10 • Number of events 1 • Participants were followed for adverse events during the entire study period, approximately 48 weeks.
Injury, poisoning and procedural complications Traumatic Hip Fracture	10.0% 1/10 • Number of events 1 • Participants were followed for adverse events during the entire study period, approximately 48 weeks.

Other adverse events

Measure	Rituximab n=10 participants at risk open label, all subjects will receive Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months
Injury, poisoning and procedural complications Infusion reaction	10.0% 1/10 • Number of events 1 • Participants were followed for adverse events during the entire study period, approximately 48 weeks.

Additional Information

Eric. L. Matteson, M.D.

Mayo Clinic

Phone: 507-284-8450

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place