Abatacept Versus Adalimumab Head-to-Head

Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N). The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage. To qualify a ACR20 score, patient must have \>=20% fewer tender joints and \>=20% fewer swollen joints and show 20% improvement from baseline in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein (CRP) test (to assess inflammation). Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.

Time frame: Day 1 to Day 365

Population: The intent to treat (ITT) analysis population was defined as all participants randomized into the study who received at least one dose of study drug. n/N = 206/318 and 208/328 in the abatacept and adalimumab arms, respectively.

Incidence Rate: (incidence/100 person-years) = number of participants with event \* 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25. The 24 Month Period includes data up to 56 days post the last dose in the 24 month period. Poisson distribution used to construct the 95% CIs.

Time frame: Day 1 to Day 729

Population: ITT population: all participants randomized into the study who received at least one dose of study drug. Participants with a pre-specified local injection site event at 24 Months: 13, 34, in abatacept and adalimumab arms, respectively. 24 Month Exposure=579.21, 532.99, respectively.

Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Time frame: Day 1 to Day 365

Population: The intent to treat (ITT) analysis population was defined as all subjects randomized into the study who received at least one dose of study drug. Poisson distribution was used to construct the 95% CIs.

Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Time frame: Day 1 to Day 729

Population: The intent to treat (ITT) analysis population was defined as all subjects randomized into the study who received at least one dose of study drug. Poisson distribution was used to construct the 95% CIs.

The induction of autoantibodies was defined as participant's antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729). Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline. Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.

Time frame: Day 1 to Day 729

Population: ITT population was defined as all participants randomized into the study who received at least one dose of study drug; number analyzed was ITT participants with data at each time point and who had negative ANA or dsDNA at baseline (m)

n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk. Proportion (%) = n/N. 12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.

Time frame: Day 1 to 12 Months

Population: The ITT analysis population was defined as all participants randomized into the study who received at least one dose of study drug. n/N = 12/318, 30/328 in abatacept and adalimumab, respectively. CI based on normal approximation.

Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729. BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign). SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films. Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (\<=) SDC(2.2). Proportion n/m (%)=number meeting criteria (n); number analyzed (m). SDC calculated as SD/sqrt(2)\*1.96/sqrt(2)with standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt). mSvdHS=summary of erosion severity in 32 hand and 12 foot joints. Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity. BL: radiographic data within 14 days or less of first dose.

Time frame: Baseline to Day 729

Population: ITT population: all subjects randomized into the study who received at least one dose of study drug. Number analyzed: m=number of ITT participants with both BL and post-BL total score: Day 365: m=295, 297;Day 729 m=257 and 260, in abatacept and adalimumab arms, respectively. n=number without progression. CI based on normal approximation.