Trial Outcomes & Findings for A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis (NCT NCT02161406)

Results Overview

Safety is measured using AEs, including clinical significant changes in vital signs, laboratory test abnormalities and clinical tolerability of abatacept, and using serious AEs

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

52 weeks

Results posted on

2020-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Abatacept 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo 125mg Placebo Placebo: 125 mg of Placebo
Overall Study STARTED	44	44
Overall Study COMPLETED	34	35
Overall Study NOT COMPLETED	10	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Abatacept 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo 125mg Placebo Placebo: 125 mg of Placebo
Overall Study Death	2	1
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	2	4
Overall Study investigator withdrew subject	3	1
Overall Study Lack of Efficacy	1	1
Overall Study relocation	0	1

Baseline Characteristics

A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo	Total n=88 Participants Total of all reporting groups
Age, Continuous	50 years STANDARD_DEVIATION 12 • n=5 Participants	49 years STANDARD_DEVIATION 13 • n=7 Participants	49 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	36 Participants n=7 Participants	76 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	37 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Disease Duration	1.66 years STANDARD_DEVIATION 0.84 • n=5 Participants	1.52 years STANDARD_DEVIATION 0.79 • n=7 Participants	1.59 years STANDARD_DEVIATION 0.81 • n=5 Participants
dcSSc Disease Duration <= 18 months	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
mRSS	23.34 units on a scale STANDARD_DEVIATION 7.947 • n=5 Participants	21.57 units on a scale STANDARD_DEVIATION 7.328 • n=7 Participants	22.45 units on a scale STANDARD_DEVIATION 7.652 • n=5 Participants
FVC% Predicted	84.19 percent predicted STANDARD_DEVIATION 13.504 • n=5 Participants	86.49 percent predicted STANDARD_DEVIATION 16.597 • n=7 Participants	85.34 percent predicted STANDARD_DEVIATION 15.087 • n=5 Participants
DLCO% Predicted, Corrected for Hemoglobin	79.57 percent predicted STANDARD_DEVIATION 18.117 • n=5 Participants	76.45 percent predicted STANDARD_DEVIATION 18.439 • n=7 Participants	78.01 percent predicted STANDARD_DEVIATION 18.241 • n=5 Participants
Patient Global Assessment	3.88 units on a scale STANDARD_DEVIATION 2.206 • n=5 Participants	4.31 units on a scale STANDARD_DEVIATION 2.561 • n=7 Participants	4.09 units on a scale STANDARD_DEVIATION 2.384 • n=5 Participants
HAQ-DI	1.14 units on a scale STANDARD_DEVIATION 0.716 • n=5 Participants	0.97 units on a scale STANDARD_DEVIATION 0.701 • n=7 Participants	1.05 units on a scale STANDARD_DEVIATION 0.710 • n=5 Participants
Physician Global Assessment	4.77 units on a scale STANDARD_DEVIATION 1.669 • n=5 Participants	4.76 units on a scale STANDARD_DEVIATION 1.665 • n=7 Participants	4.77 units on a scale STANDARD_DEVIATION 1.657 • n=5 Participants
Proportion of Participants with >= 1 Tendon Friction Rubs	19 Participants n=5 Participants	13 Participants n=7 Participants	32 Participants n=5 Participants
Proportion of Participants with >= 1 Large Joint Contractures	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Swollen Joint Count	3.64 number of swollen joints STANDARD_DEVIATION 5.620 • n=5 Participants	3.86 number of swollen joints STANDARD_DEVIATION 5.849 • n=7 Participants	3.75 number of swollen joints STANDARD_DEVIATION 5.704 • n=5 Participants
Proportion of Participants with >= 1 Swollen Joint Count	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Proportion of Participants with Previous Use of Immunosuppressives	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Proportion of Participants with Previous Use of Prednisone	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Safety is measured using AEs, including clinical significant changes in vital signs, laboratory test abnormalities and clinical tolerability of abatacept, and using serious AEs

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Proportion of Participants With at Least One Adverse Events (AEs) or Serious AEs (SAEs) in 1 Year	35 Participants	40 Participants

PRIMARY outcome

Timeframe: Baseline and 52 weeks

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The efficacy of treatment on skin fibrosis will be measured by changes from baseline to month 12 in mRSS, a measure of skin thickness. mRSS scores have a range from 0 to 51, with higher score indicating greater severity of SSc (worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline in the Modified Rodnan Skin Score (mRSS) to Month 12	-6.24 units on a scale Standard Error 1.14	-4.49 units on a scale Standard Error 1.14

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Patient global assessment for overall disease represents the patient's assessment of the patient's global scleroderma on a 0 (excellent) -10 (extremely poor) Likert scale. Higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in Patient Global Assessment for Overall Disease	-0.31 score on a scale Standard Error 0.423	-0.09 score on a scale Standard Error 0.457

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

This assessment represents the physician's assessment of the patient's current disease activity on a 0 (excellent) -10 (extremely poor) Likert scale. Higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in Physician Global Assessment for Overall Disease	-1.3 score on a scale Standard Error 0.290	-0.35 score on a scale Standard Error 0.318

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

FVC is Forced vital capacity, a measure of lung function. FVC % Predicted is calculated using equations from Hankinson \[Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999;159(1):179-87\], incorporating age, gender, and race. It is calculated as the (FVC Observed / FVC predicted) \* 100, where FVC predicted is calculated relative to a reference population.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change in % Predicted FVC	-1.34 percent predicted Standard Error 1.24	-4.13 percent predicted Standard Error 1.22

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

FVC = forced vital capacity, a measure of lung function

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in FVC (in ml)	-36.39 ml Standard Error 43.82	-121.6 ml Standard Error 46.39

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI overall score ranges from 0 (no disability) to 3 (severe disability). Higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Overall	-0.17 score on a scale Standard Error 0.07	0.11 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for disease severity ranges from 0 (no disease) to 150 (very severe). A higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in SHAQ-DI VAS - Overall Disease	-7.42 score on a scale Standard Error 5.638	3.52 score on a scale Standard Error 6.045

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much breathing problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in SHAQ-DI VAS - Breathing	9.30 score on a scale Standard Error 5.51	16.95 score on a scale Standard Error 5.85

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much Raynaud's interfered with daily activities ranges from 0 (does not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in SHAQ-DI VAS - Raynaud's	7.58 score on a scale Standard Error 6.60	-3.64 score on a scale Standard Error 7.17

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much finger ulcers interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in SHAQ-DI VAS - Burden of Digital Ulcers	-3.18 score on a scale Standard Error 5.13	8.67 score on a scale Standard Error 5.52

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much intestinal problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in SHAQ-DI VAS - GI Involvement	9.98 score on a scale Standard Error 6.00	8.01 score on a scale Standard Error 6.42

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

28 joints are assessed for swelling (positive or negative). The number of swollen joint count ranges from 0 to 28. A higher number indicates worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in Swollen Joint Count	-0.11 number of swollen joints Standard Error 0.595	-0.86 number of swollen joints Standard Error 0.601

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

28 joints are assessed for tenderness (positive or negative). The number of tender joint counts ranges from 0 to 28. A higher number indicates worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in Tender Joint Counts	-0.71 number of tender joints Standard Error 0.90	-1.47 number of tender joints Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the physical function domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Physical Function	-1.54 score on a scale Standard Error 0.65	-0.17 score on a scale Standard Error 0.69

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the anxiety domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Anxiety	-3.5 score on a scale Standard Error 1.31	-1.09 score on a scale Standard Error 1.37

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the depression domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Depression	-0.02 score on a scale Standard Error 1.13	-0.41 score on a scale Standard Error 1.20

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the fatigue domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS 29 - Fatigue	-0.65 score on a scale Standard Error 1.29	-0.98 score on a scale Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the sleep disturbance domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e.,worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Sleep Disturbance	-0.31 score on a scale Standard Error 0.57	-0.21 score on a scale Standard Error 0.62

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain interference domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Pain Interference	-4.10 score on a scale Standard Error 1.13	-1.56 score on a scale Standard Error 1.22

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the ability to participate in social roles and activities domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Ability to Participate in Social Roles & Activities	-1.11 score on a scale Standard Error 1.07	-1.26 score on a scale Standard Error 1.14

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain intensity domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS-29 - Pain Intensity	-0.72 score on a scale Standard Error 0.32	-0.18 score on a scale Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The SCTC GIT is the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Instrument. It assesses scleroderma-related gastrointestinal symptoms. The composite score ranges from 0 to 2.83; 0 indicates better health and higher score indicates worse health.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in SCTC GIT - Composite Score	0.07 score on a scale Standard Error 0.047	-0.05 score on a scale Standard Error 0.050

SECONDARY outcome

Timeframe: Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The American College of Rheumatology Combined Response Index in Systemic Sclerosis is a composite endpoint. It is determined in a 2-step process. The first step assesses whether the patient has had a significant decline in renal or cardiopulmonary involvement. If none of these apply, the second step assesses the probability of improvement by measuring changes in five outcomes and integrating them into a single number using an equation described in Khanna D, Berrocal VJ, et al. \[The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. Arthritis and Rheumatology. 2016; 68(2):299-311.\]. It incorporates changes in the modified Rodnan skin score, percent predicted forced vital capacity (FVC), patient and physician global assessments, and SHAQ-DI over 1 year. The score ranges from 0 to 1; a higher score indicates better outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
ACR CRISS at 12 Months	0.72 units on a scale Interval 0.005 to 0.994	0.02 units on a scale Interval 0.0 to 0.75

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The Patient-Reported Outcomes Measurement Information System (PROMIS) 8-question short-form health-reported quality of life measure fatigue domain was administered. The transformed score (T-score) was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS - Fatigue	-2.44 score on a scale Standard Error 1.209	-0.05 score on a scale Standard Error 1.285

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Modified Intent-to-Treat population includes all of the randomized participants who received at least one dose of study medication

The Patient-Reported Outcomes Measurement Information System (PROMIS) 4-question short-form health-reported quality of life measure sleep disturbance domain was administered. The transformed score (T-score) was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS - Sleep Disturbance	-0.31 score on a scale Standard Error 0.573	-0.21 score on a scale Standard Error 0.620

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Modified Intent-to-Treat population includes all of the randomized participants who received at least one dose of study medication

The Patient-Reported Outcomes Measurement Information System (PROMIS) 8-question short-form health-reported quality of life measure sleep impairment domain was administered. The transformed score (T-score) was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in PROMIS - Sleep Impairment	0.46 score on a scale Standard Error 1.267	-0.54 score on a scale Standard Error 1.320

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Dressing and Grooming	-0.25 score on a scale Standard Error 0.115	0.14 score on a scale Standard Error 0.119

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Hygiene	-0.08 score on a scale Standard Error 0.125	0.40 score on a scale Standard Error 0.132

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Arising	-0.23 score on a scale Standard Error 0.103	0.04 score on a scale Standard Error 0.109

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Reach	-0.12 score on a scale Standard Error 0.176	0.03 score on a scale Standard Error 0.127

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Eating	-0.22 score on a scale Standard Error 0.118	0.02 score on a scale Standard Error 0.122

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Grip	-0.29 score on a scale Standard Error 0.142	-0.22 score on a scale Standard Error 0.149

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Walking	-0.02 score on a scale Standard Error 0.100	0.18 score on a scale Standard Error 0.106

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT population includes all of the randomized participants who received at least one dose of study medication.

The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.

Outcome measures

Outcome measures
Measure	Abatacept n=44 Participants 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 Participants 125mg Placebo Placebo: 125 mg of Placebo
Change From Baseline to Month 12 in HAQ-DI - Common Daily Activities	-0.09 score on a scale Standard Error 0.113	0.08 score on a scale Standard Error 0.121

Adverse Events

Abatacept

Serious events: 9 serious events

Other events: 35 other events

Deaths: 2 deaths

Placebo

Serious events: 12 serious events

Other events: 40 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Cathie Spino

University of Michigan DCC (SABER)

Phone: 734-615-5469

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Abatacept n=44 participants at risk 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 participants at risk 125mg Placebo Placebo: 125 mg of Placebo
Infections and infestations Cellulitis of right elbow	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Infections and infestations Healthcare associated pneumonia (HCAP)	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Infections and infestations Left side mastoiditis/ abrythnitis	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Infections and infestations Paronychia	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Acute coronary syndrome	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Atrial Flutter	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Cardiac arrest	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Congestive Heart Failure	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Digital Ischemia	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders NSTEMI Myocardial Infarction	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Pulmonary Arterial Hypertension	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Pulmonary Arterial Hypertension and Pericardial Effusion	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Worsening AV block	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Anemia	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Cholecystitis	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Dysphagia due to GI dysmotility	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Dysphagia from myositis and prolonged hospitalization	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Erosive esophagitis	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders GAVE; Severe anemia	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Melena	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Pseudo obstruction of the small bowel, paralytic ileus	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Blood and lymphatic system disorders GAVE	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Psychiatric disorders Depression with Suicidal Ideation	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma (BCC)	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma In-situ Left Anterior Ear	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Renal and urinary disorders Renal crisis	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.

Measure	Abatacept n=44 participants at risk 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Abatacept: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks	Placebo n=44 participants at risk 125mg Placebo Placebo: 125 mg of Placebo
General disorders Other Non-serious Adverse Events	29.5% 13/44 • Number of events 23 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	27.3% 12/44 • Number of events 16 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Blood and lymphatic system disorders Other Non-serious Adverse Events	0.00% 0/44 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Infections and infestations Other Non-serious Adverse Events	38.6% 17/44 • Number of events 24 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	50.0% 22/44 • Number of events 39 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Musculoskeletal and connective tissue disorders Other Non-serious Adverse Events	40.9% 18/44 • Number of events 25 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	38.6% 17/44 • Number of events 23 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Nervous system disorders Other Non-serious Adverse Events	15.9% 7/44 • Number of events 7 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	15.9% 7/44 • Number of events 9 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Respiratory, thoracic and mediastinal disorders Other Non-serious Adverse Events	11.4% 5/44 • Number of events 6 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	29.5% 13/44 • Number of events 15 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Skin and subcutaneous tissue disorders Other Non-serious Adverse Events	15.9% 7/44 • Number of events 8 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	15.9% 7/44 • Number of events 12 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Renal and urinary disorders Other Non-serious Adverse Events	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	11.4% 5/44 • Number of events 6 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Cardiac disorders Other Non-serious Adverse Events	6.8% 3/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	11.4% 5/44 • Number of events 5 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Endocrine disorders Other Non-serious Adverse Events	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Ear and labyrinth disorders Other Non-serious Adverse Events	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Other Non-serious Adverse Events	25.0% 11/44 • Number of events 17 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	29.5% 13/44 • Number of events 18 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Hepatobiliary disorders Other Non-serious Adverse Events	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	9.1% 4/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Blood and lymphatic system disorders Anemia	9.1% 4/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	4.5% 2/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Diarrhea	9.1% 4/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	13.6% 6/44 • Number of events 6 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Dysphagia	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Nausea	9.1% 4/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	9.1% 4/44 • Number of events 5 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Gastrointestinal disorders Vomiting (Emesis)	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
General disorders Fatigue	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	13.6% 6/44 • Number of events 7 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
General disorders Weight Loss	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Infections and infestations Upper Respiratory Infection	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	20.5% 9/44 • Number of events 11 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Infections and infestations Urinary Tract Infection	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	9.1% 4/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Nervous system disorders Headache	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	13.6% 6/44 • Number of events 8 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Skin and subcutaneous tissue disorders Pruritis (Itching)	9.1% 4/44 • Number of events 4 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	2.3% 1/44 • Number of events 1 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.
Skin and subcutaneous tissue disorders Rash	6.8% 3/44 • Number of events 3 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.	4.5% 2/44 • Number of events 2 • 52 weeks Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.