Methotrexate-Inadequate Response Autoinjector Device Sub Study

Abatacept SC was self-administered with a prefilled syringe every 7 days for the first 4 weeks until Day 29; Blood samples for PK were taken pre-dose (0 hour) on Days 29 and 113. Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Steady-state trough observed concentration in serum (Cminss) was measured in micrograms/milliliter (μg/mL). Adjusted geometric mean and 90% confidence interval (CI) are presented.

Time frame: Day 29, Day 113

Population: The primary PK analysis population is a subset of the Treated Analysis population with (1) viable Cmin data on both substudy Days 29 and 113 (2) no missed Abatacept dose during the substudy period.

Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken on Days 1 and 22 at 0 hour (predose), Day 24 at 48 hour (h) post dose, Day 25 at 72 h post dose, Day 26 at 96 h post dose and Day 29 at 0 h (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy; Blood samples for PK were taken on Day 106 at 0 h (predose), Day 108 at 48 h post dose, Day 109 at 72 h post dose, Day 110 at 96 h post dose and at Day 113 0h (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. AUC(TAU) where TAU = 168 hours was calculated in µg\*h/mL

Time frame: Days 22, 24, 25, 26,29 (prefilled syringe); Days 106, 108, 109, 110, 113 (autoinjector)

Population: PK population: A subset of the treated population with at least 1 PK sample collected/assessed for serum concentration after start of autoinjector. Participants did not miss either 0-hour or 168-hour samples and not missed 2 or more time points in the PK profile.

Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken at 0 hour (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy. Blood samples for PK were taken at 0 hour (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. Steady-state trough observed concentration in serum (Cminss) was measured in micrograms/milliliter (μg/mL).

Time frame: Days 22, 29, 57, 85, 106, and 113

Population: PK population: A subset of the treated population with at least 1 PK sample collected/assessed for serum concentration after start of autoinjector and with Cmin obtained appropriately (7 days + or -3 days after the previous dose).

Serum samples for immunogenicity were evaluated for presence of anti-abatacept antibodies using a validated bridging ECL on Day 29 and Day 113. The ECL assay differentiated between 2 antibody specificities: the immunoglobulin (Ig) G and/or junction region and cytotoxic leukocyte antigen 4 (CTLA4) and possibly Ig. A positive immunogenicity response relative to baseline was defined as: A missing baseline immunogenicity measurement and a positive analytical laboratory reported immunogenicity response post-baseline; A negative baseline immunogenicity response and a positive analytical laboratory reported immunogenicity response post-baseline; A positive baseline immunogenicity response and a positive analytical laboratory reported immunogenicity response post-baseline that has a titer value strictly greater than the baseline titer value.

Time frame: Days 29 and 113

Population: A subset of the treated analysis population for whom at least 1 immunogenicity sample was collected and assessed for serum anti-abatacept antibodies, were summarized.

Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken on Days 1 and 22 at 0 hour (predose), Day 24 at 48 hour (h) post dose, Day 25 at 72 h post dose, Day 26 at 96 h post dose and Day 29 at 0 h (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy; Blood samples for PK were taken on Day 108 at 48 h post dose, Day 109 at 72 h post dose, Day 110 at 96 h post dose and at Day 113 0h (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. Cmax was measured in μg/mL.

Time frame: Days 22, 24, 25, 26, 29 (prefilled syringe); Days 106, 108, 109, 110, 113 (autoinjector)

Population: PK population: A subset of the treated population with at least 1 PK sample collected/assessed for serum concentration after start of autoinjector. Participants did not miss either 0-hour or 168-hour samples and not missed 2 or more time points in the PK profile.

Abatacept SC was self-administered with a BD Hypak™ Physiolis prefilled syringe every 7 days for the first 4 weeks of the substudy until Day 29; Blood samples for PK were taken on Days 1 and 22 at 0 hour (predose), Day 24 at 48 hour (h) post dose, Day 25 at 72 h post dose, Day 26 at 96 h post dose and Day 29 at 0 h (predose). On substudy Day 29, participants were switched from the prefilled syringe to the autoinjector. Participants continued to self-administer abatacept with the autoinjector every 7 days following Day 29 for the remaining 3 months of the substudy; Blood samples for PK were taken on Day 108 at 48 h post dose, Day 109 at 72 h post dose, Day 110 at 96 h post dose and at Day 113 0h (predose). Serum concentrations of abatacept were analyzed using a validated ELISA. Tmax was measured in hours (h).

Time frame: Days 22, 24, 25, 26, 29 (prefilled syringe); Days 106, 108, 109, 110,113 (autoinjector)

Population: PK population: A subset of the treated population with at least 1 PK sample collected/assessed for serum concentration after start of autoinjector. Participants did not miss either 0-hour or 168-hour samples and not missed 2 or more time points in the PK profile.