Phase IIIB Switching From Intravenous to Subcutaneous Study

An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators. Systemic injection reaction occurring ≤ 24 hours after dosing.

An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators.

LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Hemoglobin (g/dL) >3 decrease from preRx. Hematocrit (%)<0.75*preRx. Erythrocytes (*10^6 c/uL) <0.75*preRx. Platelet count (*10^9 c/L) <0.67*LLN or 1.5*ULN or, if preRx<LLN, use <0.5*preRx and <100,000 mm^3. Leukocytes (*10^3 c/uL) <0.75*LLN or >1.25*ULN or, if preRx<LLN, use <0.8*preRx or >ULN or, if preRx>ULN, use >1.2*preRx or <LLN. Eosinophils >0.750*10^3 c/uL. Lymphocytes <0.750*10^3 c/uL or >7.50*10^3 c/uL.

LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (U/L) >2*ULN or if preRx>ULN, use 3*preRx. Alanine aminotransferase (U/L)>3*ULN or if preRx>ULN, use >4*preRx. G-glutamyl transferase (U/L)>2*ULN or if preRx>ULN, use >3*preRx. Blood urea nitrogen (mg/dL)>2*preRx. Creatinine (mg/dL)>1.5*preRx.

LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Sodium: <0.95*LLN or >1.05*ULN or if preRx<LLN, <0.95*preRx or >ULN, or if preRx>ULN,>1.05*preRx or <LLN. Potassium,serum: <0.9*LLN or >1.1*ULN or if preRx<LLN, use <0.9*preRx or >ULN or if preRx>ULN, 1.1*preRx or <LLN. Phosphorus: 0.75*LLN or 1.25*ULN or, if preRx<LLN, <0.67*preRx or >ULN or, if preRx>ULN, <LLN.

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality: .

preRX=pretreatment. For all values analyzed (protein, urine; glucose, urine; blood, urine: leukocyte esterase, urine; white blood cells, urine; red blood cells, urine): If missing preRx, use >=2 or, if value >= 4, or if preRx=0 or 0.5, use >=2 or, if preRx= 1, use >=3 or, if preRx=2 or 3, use >=4.

AEs of special interest are AEs that may be associated with the use of immunomodulatory drugs, such as infections, malignancies, autoimmune disorders, and injection reactions (defined as local injection site reactions and systemic injection reactions occurring within 24 hours of subcutaneous injection).

BP was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.

Heart rate was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.

Temperature was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.

Cmin of abatacept was determined from serum samples.

Using the ELISA, any positive (titer of 400 or greater) postbaseline sample was classified as positive immunogenicity. The percentage of participants with at least 1 positive antibody response (anti-abatacept and/or anti-CTLA4-T) during the 85 days was tabulated by antibody specificity and overall.

Number of participants was tabulated using ECL assay with at least 1 positive abatacept-induced immunogenic response (CTLA4 and possibly Ig, Ig and/or Junction Region) in the first 85 days. Positive response (titers >10) included:

• A missing baseline immunogenicity measurement and a positive immunogenicity response postbaseline
• A negative baseline immunogenicity response and a positive immunogenicity response postbaseline
• A positive baseline immunogenicity response and a positive immunogenicity response postbaseline that has a titer value strictly greater than the baseline titer value

The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

LDAS is defined as DAS 28-CRP ≤3.2. DAS 28-CRP remission is defined as DAS 28-CRP <2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

The HAQ-DI assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories is divided by the number of categories answered, yielding a score from 0-3.