A Comparative Study Between PF-06410293 and Humira® in Combination With Methotrexate in Participants With Active Rheumatoid Arthritis

Area under the serum concentration curve from time 0 to end of dosing interval (tau), where dosing interval was once every two weeks. The geometric coefficient of variation is expressed in percentage.

Time frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30)

Population: PK population included all randomized participants who were dosed to initiate the Week 30 steady-state PK profile and remained on background methotrexate with no major protocol deviations influencing the PK assessment. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Since time points for analysis for this outcome measure were falling in TP4, hence only switching and non-switching arms data were reported.

Cmax refers to maximum observed serum concentration of drug. The geometric coefficient of variation is expressed in percentage.

Time frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30)

Population: Pharmacokinetic (PK) population included all randomized participants who were dosed to initiate the week 30 steady-state PK profile and remained on background methotrexate with no major protocol deviations influencing the PK assessment. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Since time points for analysis for this outcome measure were falling in TP4, hence only switching and non-switching arms data were reported.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). The geometric coefficient of variation is expressed in percentage.

Time frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30)

Population: PK population included all randomized participants who were dosed to initiate the Week 30 steady state PK profile and remained on background methotrexate with no major protocol deviations influencing the PK assessment. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Since time points for analysis for this outcome measure were falling in TP4, hence only switching and non-switching arms data were reported.

Cav was defined as average serum concentration over the dosing interval. The geometric coefficient of variation is expressed in percentage.

Time frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30)

Population: PK population included all randomized participants who were dosed to initiate the Week 30 steady state PK profile and remained on background methotrexate with no major protocol deviations influencing the PK assessment. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. Since time points for analysis for this outcome measure were falling in TP4, hence only switching and non-switching arms data were reported.

Pulse rate was measured in a supine position using an automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

Time frame: Baseline and Week 32 (EOT/ET)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

Time frame: Baseline and Week 32 (EOT/ET)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

SBP and DBP were measured in a supine position using an automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

Time frame: Baseline and Week 32 (end of treatment [EOT]/early termination [ET])

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

Time frame: Baseline and Week 32 (EOT/ET)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Serum samples were analyzed using a validated ECL immunoassay for ADA assessment. Endpoint titer was defined as log10 of the reciprocal of the ADA serum dilution at which the sample response was equal to the cut-point of the assay.

Time frame: Week 10, 16, 22, 24, 26, 28, 30, 32

Population: Safety randomized population included all participants who were randomized and received at least one dose of investigational product following the randomization at Study Week 10. Here, 'Number Analyzed' signifies participants evaluable with ADA non-missing values at specific time points.

Serum samples were analyzed using a validated ECL immunoassay for ADA assessment. Endpoint titer was defined as log10 of the reciprocal of the NAb serum dilution at which the sample response was equal to the cut-point of the assay.

Time frame: Week 10, 16, 22, 24, 26, 28, 30, 32

Population: Safety randomized population included all participants who were randomized and received at least one dose of investigational product following the randomization at Study Week 10. Here, 'Number Analyzed' signifies participants evaluable with NAb non-missing values at specific time points.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study. TEAEs were related to Covid-19.

Time frame: Day 1 up to maximum of 10 Weeks

Population: Safety population for TP1 included all participants who were enrolled and received at least one dose of study treatment in TP1.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study. TEAEs were related to Covid-19.

Time frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an TEAE in TP1 indicating that the AE caused the participant to be discontinued from the study.

Time frame: Day 1 up to maximum of 10 Weeks

Population: Safety population for TP1 included all participants who were enrolled and received at least one dose of study treatment in TP1.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study.

Time frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10.

Serum samples were analyzed using a validated electrochemoluminescent (ECL) immunoassay for ADA assessment. Samples positive for ADA were further tested for neutralizing activity using a validated cell based NAb assay. ADA positive was defined as ADA titer \>=1.88 while NAb positive was defined as NAb titer \>=0.70.

Time frame: Week 10, 16, 22, 24, 26, 28, 32

Population: Safety randomized population included all participants who were randomized and received at least one dose of investigational product following the randomization at Study Week 10. For ADA: Number Analyzed = all participants assessed for ADA measurement at specific time points. For Nab: Number Analyzed = all participants with ADA positive results assessed for Nab measurement at specific time points.

Blood samples were collected for analysis of clinical chemistry parameters: ALT increased, alkaline phosphatase increased (ALP), aspartate aminotransferase increased (AST), blood bilirubin increased, creatinine increased, hypercalcemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hyponatremia. Laboratory parameters were graded according to NCI-CTC version 4.03 where, grade 0= within normal limits; Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences and Grade 5: death. Categories with at least 1 non-zero value were reported.

Time frame: Post randomization up to end of study treatment (maximum of 22 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of dose of investigational product following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Here, Number Analyzed signifies participants evaluable for each row.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs were graded using the Common Terminology Criteria for Adverse Events where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening consequences; urgent intervention indicated; and grade 5= death related to AE. Number of participants with grade 3 or higher TEAEs were presented.

Time frame: Day 1 up to maximum of 10 Weeks

Population: Safety population for TP1 included all participants who were enrolled and received at least one dose of study treatment in TP1.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs were graded using the Common Terminology Criteria for Adverse Events where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening consequences; urgent intervention indicated; and grade 5= death related to AE. Number of participants with grade 3 or higher TEAEs were presented.

Time frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10.

Blood samples were collected for the analysis of following hematology parameters: anemia, hemoglobin increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased. Laboratory parameters were graded according to National Cancer Institute-CTC version 4.03 where, Grade 0= within normal limits; Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences and Grade 5: death. Categories with at least 1 non-zero value were reported in this outcome measure.

Time frame: Post randomization up to end of study treatment (maximum of 22 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of dose of investigational product following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Here, Number Analyzed signifies participants evaluable for each row.

Blood samples were collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, alanine aminotransferase \[ALT\], blood urea nitrogen \[BUN\], creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.

Time frame: Day 1 up to maximum of 10 Weeks

Population: Safety population for TP1 included all participants who were enrolled and received at least one dose of study treatment in TP1. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Blood samples were collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, ALT, BUN, creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.

Time frame: Post randomization up to end of study treatment (maximum of 22 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of dose of investigational product following the randomization at Study Week 10. Here Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

In this outcome measure, liver function laboratory parameters, which included: normal bilirubin and AST/ALT, Temple's Corollary (AST/ALT \[more than or equal to\] \>=3\*upper limit normal \[ULN\] and normal bilirubin), Gilbert's Syndrome or cholestasis (normal AST/ALT and bilirubin \>=2\*ULN) and Potential Hy's Law Cases (AST/ALT \>=3\*ULN and Bilirubin\>=2\*ULN) according to eDISH criteria, were reported.

Time frame: Post randomization up to end of study treatment (maximum of 22 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of dose of investigational product following the randomization at Study Week 10. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

In this outcome, participants who were ADA negative during TP1 were assessed in TP2 and beyond per visit for their ADA status at the time of start of their potential immunogenic AEs including ISRs, medically evaluated board SMQ of potential hypersensitivity (anaphylactic reactions, hypersensitivity and angioedema), medically evaluated AEs meeting Sampson criteria, cytokine storm and DIR. ADA negative was defined as ADA titer \<1.88.

Time frame: TP2 and Beyond: Week 16, 22, 24, 26, 28, 30, 32

Population: Safety randomized population included all participants who were randomized and received at least one dose of investigational product following the randomization at Study Week 10.Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Here, Number Analyzed signifies participants evaluable for specific rows.

In this outcome, participants who were antidrug antibody (ADA) positive during TP1 were assessed in TP2 and beyond per visit for their ADA status at the time of start of their potential immunogenic AEs including ISRs, medically evaluated board standard MedDRA query (SMQ) of potential hypersensitivity (anaphylactic reactions, hypersensitivity and angioedema), medically evaluated AEs meeting Sampson criteria, cytokine storm and delayed immune responses (DIR). ADA positive was defined as ADA titer \>=1.88.

Time frame: TP2 and Beyond: Week 16, 22, 24, 26, 28, 30, 32

Population: Safety randomized population included all participants who were randomized and received at least one dose of investigational product following the randomization at Study Week 10.Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Here, Number Analyzed signifies participants evaluable for specific rows.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs included both serious and all non-serious AEs. TEAEs and serious TEAEs related to Covid-19 as per investigator's assessment were presented.

Time frame: Day 1 up to maximum of 10 Weeks

Population: Safety population for TP1 included all participants who were enrolled and received at least one dose of study treatment in TP1.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. TEAEs and serious TEAEs related to Covid-19 as per investigator's assessment were presented.

Time frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10.

AEs of special interest (AESI) included: hypersensitivity events (anaphylactic reaction, hypersensitivity, angioedema, delayed immune responses and injection site reactions \[ISRs\]); blood and lymphatic system events (white blood cell disorders and anemias nonhemolytic and marrow depression); cardiovascular events (cardiac failure, hypertension and myocardial infarction); demyelinating conditions, gastric/hepatic events (gastrointestinal perforation, ulceration, hemorrhage or obstruction and hepatic disorders); infections and infestations (including TB and other opportunistic infections); malignancies (neoplasms benign, malignant and unspecified \[including cysts and polyps\]) and lupus like syndrome. TEAE was defined as any AE that occurred after the first dose of study treatment administered after randomization in TP2. Number of participants with any AESI were presented in this outcome measure.

Time frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10.

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE for TP2 and beyond was defined as any AE that occurred after administering the first dose of study treatment after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs.

Time frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks)

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10.

An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs included both serious and all non-serious AEs.

Time frame: Day 1 up to maximum of 10 Weeks

Population: Safety population for TP1 included all participants who were enrolled and received at least one dose of study treatment in TP1.

Ctrough was defined as pre-dose serum concentration during multiple dosing and observed directly from data.

Time frame: Pre-dose on Day 1, 71,113, 155, 169, 183, 197 and 211

Population: Safety randomized population included all participants who were randomized and received at least one dose of study treatment following the randomization at Study Week 10. Data for Days 1 and 71 were identified retrospectively for participants in the safety randomized population, hence included in the switching and non-switching reporting groups. Here, Number Analyzed signifies participants evaluable for each specified category.

Tmax is the time taken (in hours) to reach the maximum serum drug concentration.

Time frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30)

Population: PK population included all randomized participants who were dosed to initiate the Week 30 steady state PK profile and remained on background methotrexate with no major protocol deviations influencing the PK assessment. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Since time points for analysis for this outcome measure were falling in TP4, hence only switching and non-switching arms data were reported.