Substudy - Low Dose of Abatacept in Subjects With Rheumatoid Arthritis

An event of disease relapse was defined as additional Disease-modifying antirheumatic drug (DMARD) therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 C-reactive protein (CRP) score >=3.2 at 2 consecutive visits. Time to disease relapse was evaluated using life tables (Kaplan-Meier Cumulative Percentage of Events of Disease Relapse).

Disease relapse is defined as additional DMARD therapy given, or 2 or more courses of high steroids given, or return to abatacept 10 mg/kg (rescue medication given), or DAS28 CRP score >= 3.2 at 2 consecutive visits.

Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).

Mean baseline DAS28 CRP values for the cohort of participants with serum samples available at that timepoint. DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).

DAS 28 is a continuous variable which is a composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28 joints, CRP in mg/L and subject assessment of disease activity measure on a VAS of 100 mm. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis (>5.1=high disease activity; <3.2=low disease activity; <2.6=remission).

Additional DMARD therapy is defined as a re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD.

A course of high dose steroids is defined as a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals).

All subjects in the sub-study randomized to receive double-blind abatacept 5 mg/kg or 10 mg/kg. Subjects rescued to open-label treatment received abatacept 10 mg/kg.

Modified therapy=additional DMARD therapy, 2 or more courses of high dose steroids or rescue medication. Additional DMARD therapy=re-introduction of methotrexate (MTX), an increase of at least 2.5 mg of MTX, or the addition of at least 1 DMARD. A course of high dose steroids=a course of intramuscular, intravenous, or high dose oral corticosteroids (use of > 10 mg/day equivalent of prednisone for a minimum of 3 consecutive days or for those subjects who had continued use for long durations of time, each course was determined by 28 day intervals). Rescue medication=abatacept 10 mg/kg.

Loss of remission is defined as DAS 28 CRP >=2.6.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Infection and Infestation AEs = any AE within the System Organ Class Infection and Infestation.

All neoplasms were assessed by medical review as to whether or not the event was malignant.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Acute Infusional AE= a subset of the peri-infusional AEs with onset during the first hour after the start of the study drug infusion. A total of 105 infusional events were prespecified in the protocol.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Peri-infusional AE=a pre-specified infusional AE occuring during the first 24 hours after the start of study drug infusion.A total of 105 infusional events were prespecified in the protocol. GDASC=General Disorders and Administration Site Conditions, RTMD=Respiratory, Thoracic and Mediastinal Disorders.

A total of 127 autoimmune disorders were prespecified in the protocol. MCTD=Musculoskeletal and Connective Tissue Disorders

Not evaluated: high hemoglobin,high hematocrit,high erythrocytes,high neutrophils+bands(N+B),low monocytes,low basophils,low eosinophils,low alkaline phosphatase(ALP),low aspartate aminotransferase(AST),low alanine aminotransferase(ALT),low G-Glutamyl transferase(GGT),low total bilirubin,low blood urea nitrogen,low creatinine,high albumin,low uric acid,low urine protein,low urine glucose,low urine blood,low urine leukocyte esterase,low urine white blood cells,low red blood cells.Pre Rx=pretreatment,(*)Lymphocytes(c/uL):Low<.750x10^3,High>7.50x10^3.(*)Eosinophils:>.750x10^3 c/uL.

Clinical significance was determined by investigator. Parameters include blood pressure, heart rate, respiration rate, and temperature.

A positive antibody response to Abatacept (measured by the ECL assay) is further classified as a positive response for either Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Possibly immunoglobulin (Ig)' or 'Ig and/or Junction Region'