Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)

DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR and RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Least square (LS) mean and standard error (SE) at Week 24 were obtained using Mixed-effect model with repeated measures (MMRM) approach.

Time frame: Baseline, Week 24

Population: Intent-to-treat (ITT) population included all participants. Overall Number of Participants Analyzed = participants with DAS28-ESR assessment at both baseline and Week 24.

CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global assessment of disease activity (in cm), and physician's global assessment of disease activity (VAS in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. LS means and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with CDAI assessment both at baseline and Week 24.

DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with DAS28-CRP score assessment at both baseline and Week 24.

EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. EQ-5D was specifically included to address concerns regarding the health economic impact of RA. EQ-5D-3L comprises of 5 questions on mobility, self-care, pain/discomfort, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems). The 5-dimensional 3-level systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-3L-VAS records the participant's self-rated health on a vertical VAS that allows the participants to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with EQ-5D-3L score assessment both at baseline and Week 24. Here, Number Analyzed = participants with available data for specified category for each arm, respectively.

The FACIT-F is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranged from 0 to 52, where higher score corresponds to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 by MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with FACIT-F score assessment both at baseline and Week 24.

Physical function was assessed by HAQ-DI. It consisted of at least 2 or 3 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with HAQ-DI assessment at both baseline and Week 24.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). An elevated CRP level is considered a non-specific marker for RA. A decrease indicates improvement. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with CRP assessment both at baseline and Week 24.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). The ESR is a blood test that can reveal inflammatory activity. Inflammation can cause the cells to clump together. The farther the red blood cells have descended, the greater the inflammatory response. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with ESR assessment both at baseline and Week 24.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). Physician global VAS & participant global VAS was done on 100 mm horizontal anchored VAS, ranging from 0 no arthritis activity to 100 maximal arthritis activity and Pain VAS on 100 mm VAS, ranging from 0 no pain to 100 worst pain. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with individual ACR components assessment both at baseline and Week 24. Here, Number Analyzed = participants with available data for specified category for each arm, respectively.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & acute phase reactant (hs-CRP and ESR levels). 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with TJC and SJC assessment both at baseline and Week 24.

RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with morning stiffness VAS assessment both at baseline and Week 24.

RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well-being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Each NRS is assessed as a number between 0 and 10 that corresponds to the 7 domains. The values for each of these domains are weighed by participant assessment of relative importance and combined in a single score with a total score range of 0 (not affected, very good) to 10 (most affected). LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with RAID assessment both at baseline and Week 24.

SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures HRQL in the last 4 weeks covering 2 summary measures: PCS and MCS. PCS with 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with SF-36 - mental health component summary score assessment both at baseline and Week 24.

SF-36 is a generic 36-item questionnaire consisting of 8 sub-scales, measures health-related quality of life (HRQL) in the last 4 weeks covering 2 summary measures: PCS and mental component summary (MCS). PCS with 4 sub-scales: physical function, role limitations due to physical problems, pain, and general health perception; and MCS with 4 sub-scales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a sub-scale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same sub-scale give the sub-scale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Both PCS and MCS range from 0-100 with higher scores indicating better physical and mental health. LS mean and SE at Week 24 by MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with SF-36 PCS score assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT Population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by \>= 50% in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed =participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by \>= 50% in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participants was reported. LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire is interviewer-administered and based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained using MMRM approach.

Time frame: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA values available: Individual items assessment both at baseline and Week 24.

Number of participants with different post-baseline status of HDL: \< 40 mg/dL, 40 - \< 60 mg/dL, \>= 60 mg/dL, is reported here.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant abnormalities: * Sodium: \<=129 mmol/L; \>=160 mmol/L. * Potassium: \<3 mmol/L; \>=5.5 mmol/L. * Chloride: \<80 mmol/L; \>115 mmol/L.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant abnormalities: * Alanine Aminotransferase (ALT): \>1 ULN and \<=1.5 ULN; \>1.5 ULN and \<=3 ULN; \>3 ULN and \<=5 ULN; \>5 ULN and \<=10 ULN; \>10 ULN and \<=20 ULN; \>20 ULN. * Aspartate aminotransferase (AST): \>1 ULN and \<=1.5 ULN; \>1.5 ULN and \<=3 ULN; \>3 ULN and \<=5 ULN; \>5 ULN and \<=10 ULN; \>10 ULN and \<=20 ULN; \>20 ULN. * Alkaline phosphatase: \>1.5 ULN. * Total bilirubin (TBILI): \>1.5 ULN; \>2 ULN. * Conjugated bilirubin (CBILI): \>1.5 ULN. * Unconjugated bilirubin: \>1.5 ULN, \>2 ULN. * ALT \>3 ULN and TBILI \>2 ULN. * CBILI \>35% TBILI and TBILI \>1.5 ULN. * Albumin: \<=25 g/L.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant abnormalities: * Glucose: \<=3.9 millimole/liter (mmol/L) and \<LLN; \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]). * Hemoglobin A1c (HbA1c): \>8%. * Total cholesterol: \>=6.2 mmol/L; \>=7.74 mmol/L. * LDL cholesterol: \>=4.1 mmol/L; \>=4.9 mmol/L. * Triglycerides: \>=4.6 mmol/L; \>=5.6 mmol/L.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'number analyzed' = participants with available data for each specified category.

Criteria for potentially clinically significant laboratory abnormalities included: * Hemoglobin (Hb): less than or equal to (\<=) 115 grams per liter (g/L) (Male), \<= 95 g/L (Female); greater than or equal to (\>=) 185 g/L (18.5 g/dL) (Male), \>= 165 g/L (16.5 g/dL) (Female); Decrease From Baseline (DFB) = 20 g/L (2 g/dL). * Hematocrit: \<= 0.37 volume/volume (v/v) (Male); \<= 0.32 v/v (F); \>= 0.55 v/v (Male); \>= 0.5 v/v (Female). * Red Blood Cells (RBCs): \>=6 Tera/ liter (L). * Platelets: \< 50 Giga/L, 50 - 100 Giga/L, \>= 700 Giga/L. * White blood cells (WBC): \< 3.0 Giga/L (Non-Black); \< 2.0 Giga/L (Black), \>= 16.0 Giga/L. * Neutrophils: \< 1.0 Giga/L, \< 1.5 Giga/L (Non-Black); \< 1.0 Giga/L (Black). * Lymphocytes: \< 0.5 Giga/L, \>= 0.5 Giga/L - lower limit of normal (LLN), \> 4.0 Giga/L. * Monocytes: \> 0.7 Giga/L. * Basophils: \> 0.1 Giga/L. * Eosinophils: \> 0.5 Giga/L or \> upper limit of normal (ULN) (if ULN \>= 0.5 Giga/L).

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'number analyzed' = participants with available data for each specified category.

Criteria for potentially clinically significant abnormalities: * Creatinine: \>=150 micromol/L (adults); \>=30% change from baseline, \>=100% change from baseline. * Creatinine clearance: \<15 mL/min; \>=15 to \<30 mL/min; \>=30 to \<60 mL/min; \>=60 to \<90 mL/min. * Blood urea nitrogen: \>=17 mmol/L. * Uric acid: \<120 micromol/L; \>408 micromol/L.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria with potentially clinically significant urine abnormalities: pH: \<= 4.6; pH: \>= 8.0.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant ECG abnormalities: * Heart rate (HR): \<50 beats per minute (bpm); \<50 bpm and DFB \>=20 bpm; \<40 bpm; \<40 bpm and DFB \>=20 bpm; \<30 bpm; \<30 bpm and DFB \>=20 bpm; \>90 bpm; \>=90 bpm and increase from baseline (IFB) \>=20 bpm; \>100 bpm; \>=100 bpm and IFB \>=20 bpm; \>120 bpm; \>=120 bpm and IFB \>=20 bpm. * PR Interval: \>200 millisecond (ms); \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB \>=25%. * QRS Interval: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25%. * QT Interval: \>500 ms. * QTc Bazett (QTc B): \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms. * QTc Fridericia (QTc F): \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP) supine: \<=95 mmHg and DFB\>=20 mmHg; \>=160 mmHg and IFB \>=20 mmHg. Diastolic blood pressure (DBP) supine: \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg. SBP (Orthostatic): \<=-20 mmHg. DBP (Orthostatic): \<=-10 mmHg. HR supine: \<=50 bpm and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm. Weight: \>=5% DFB; \>=5% IFB.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB Period). Here, 'number analyzed' = participants with available data for each specified category.

Adverse event (AE) was defined as any untoward medical occurrence in participant who received investigational medicinal product (IMP) and did not necessarily had to have causal relationship with treatment. All reported AEs are TEAEs developed/worsened during 'on treatment period' (time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized//DB treatment). SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on safety population (DB period) which consisted of all randomized participants who received at least one dose of study medication analyzed according to the treatment they have actually received.

Anti-drug antibody response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs was defined as a participant with no positive assay response at baseline but with a positive assay response during the TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TEAE period. TEAE period: time from first dose of study drug up to day before first dose of open-label treatment for participants who completed 24-week randomized/DB treatment.

Time frame: From Week 0 to Week 24

Population: Analysis was performed on ADA population which consisted of all participants who had signed informed consent and had been allocated to a randomized treatment; received at least 1 dose or part of a dose of IMP with at least 1 post-dose, evaluable ADA sample. Data for this outcome measure was not planned to be collected and analyzed for Adalimumab 40 mg/Sarilumab 200 mg arm.

ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant's assessment of pain (measured on 0 \[no pain\]-100 mm \[worst pain\] VAS); participant's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); physician's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 \[better physical function\] - 3 \[worst physical function\]). ACR20 was defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments. Participants were analyzed as non-responders from the time they discontinued treatment.

Time frame: Week 24

Population: ITT population.

ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (C-reactive protein \[CRP\] level); participant's assessment of pain (measured on 0 \[no pain\]-100 mm \[worst pain\] VAS); participant's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); physician's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); participant's assessment of physical function (measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\], with scoring range of 0 \[better physical function\] - 3 \[worst physical function\]). ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. Participants were analyzed as non-responders from the time they discontinued treatment.

Time frame: Week 24

Population: ITT Population.

ACR responses are assessed with a composite rating scale of the ACR that includes 7 variables: TJC (68 joints); SJC (66 joints); levels of an acute phase reactant (CRP level); participant's assessment of pain (measured on 0 \[no pain\]-100 mm \[worst pain\] VAS); participant's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); physician's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); participant's assessment of physical function (measured by HAQ-DI, with scoring range of 0 \[better physical function\] - 3 \[worst physical function\]). ACR70 was defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments. Participants were analyzed as non-responders from the time they discontinued treatment.

Time frame: Week 24

Population: ITT Population.

CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: SJC (28 joints), TJC (28 joints), participant's global assessment of disease activity (in cm), and physician's global assessment of disease activity (in cm). Total score ranges from 0 to 76 with a lower score indicating less disease activity. Participants were analyzed as non-responders from the time they discontinued treatment.

Time frame: Week 24

Population: ITT population.

DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by hs-CRP in mg/L. The DAS28-CRP score provides a number indicating the current disease activity of the RA. DAS28-CRP total score ranges from 2-10. A DAS28-CRP score above 5.1 means high disease activity, whereas a DAS28-CRP score below 3.2 indicates low disease activity and a DAS28-CRP score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.

Time frame: Week 24

Population: ITT population.

DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants who discontinued treatment prior to Week 24 were analyzed as non-responders.

Time frame: Week 24

Population: ITT Population.

DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Participants were analyzed as non-responders from the time they discontinued treatment.

Time frame: Week 24

Population: ITT Population.

Data for this outcome measure was not planned to be collected and analyzed for Adalimumab 40 mg/Sarilumab 200 mg arm.

Time frame: Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, and 24

Population: Analysis was performed on Pharmacokinetics population (DB period) which consisted of all randomized Sarilumab participants who received at least 1 dose of IMP with at least one post-dose, non-missing concentration of functional Sarilumab in serum concentration value. Here, 'number analyzed' = participants with available data for each specified category.

Anti-drug antibody response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs was defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the entire TEAE period. Entire TEAE period: last OLE dose - first DB dose date + 6 weeks (follow-up), regardless of unplanned intermittent discontinuations.

Time frame: From Week 0 up to last dose in OLE + 6 weeks of follow-up (i.e. up to Week 306)

Population: Analysis was performed on immunogenicity population which consisted of all participants who received at least 1 dose or part of a dose of IMP with at least 1 post-dose, evaluable ADA sample.

Number of participants with different post-baseline status of HDL: \< 40 mg/dL, 40 - \< 60 mg/dL, \>=60 mg/dL, is reported here.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant abnormalities: * Sodium: \<=129 mmol/L; \>=160 mmol/L. * Potassium: \<3 mmol/L; \>=5.5 mmol/L. * Chloride: \<80 mmol/L; \>115 mmol/L.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant laboratory abnormalities included: * Hb: \<=115 g/L (Male), \<= 95 g/L (Female); \>=185 g/L (18.5 g/dL) (Male), \>= 165 g/L (16.5 g/dL) (Female); DFB \>= 20 g/L (2 g/dL). * Hematocrit: \<= 0.37 v/v (Male); \<= 0.32 v/v (Female); \>= 0.55 v/v (Male); \>= 0.5 v/v (Female). * RBCs: \>=6 Tera/ L. * Platelets: \< 50 Giga/L, \>=50 - 100 Giga/L, \>= 700 Giga/L. * WBC: \< 3.0 Giga/L (Non-Black); \< 2.0 Giga/L (Black), \>= 16.0 Giga/L. * Neutrophils: \< 1.0 Giga/L, \< 1.5 Giga/L (Non-Black); \< 1.0 Giga/L (Black). * Lymphocytes: \< 0.5 Giga/L, \>= 0.5 Giga/L - LLN, \> 4.0 Giga/L. * Monocytes: \> 0.7 Giga/L. * Basophils: \> 0.1 Giga/L. * Eosinophils: \> 0.5 Giga/L or \> ULN (if ULN \>= 0.5 Giga/L).

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant abnormalities: * ALT: \>1 ULN and \<=1.5 ULN; \>1.5 ULN and \<=3 ULN; \>3 ULN and \<=5 ULN; \>5 ULN and \<=10 ULN; \>10 ULN and \<=20 ULN; \>20 ULN. * AST: \>1 ULN and \<=1.5 ULN; \>1.5 ULN and \<=3 ULN; \>3 ULN and \<=5 ULN; \>5 ULN and \<=10 ULN; \>10 ULN and \<=20 ULN; \>20 ULN. * Alkaline phosphatase: \>1.5 ULN. * TBILI: \>1.5 ULN; \>2 ULN. * CBILI: \>1.5 ULN. * Unconjugated bilirubin: \>1.5 ULN, \>2 ULN. * ALT \>3 ULN and TBILI \>2 ULN. * CBILI \>35% TBILI and TBILI \>1.5 ULN. * Albumin: \<=25 g/L.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant abnormalities: * Glucose: \<=3.9 mmol/L and \<LLN; \>=11.1 mmol/L (unfas) or \>=7 mmol/L (fas). * HbA1c: \>8%. * Total cholesterol: \>=6.2 mmol/L; \>=7.74 mmol/L. * LDL cholesterol: \>=4.1 mmol/L; \>=4.9 mmol/L. * Triglycerides: \>=4.6 mmol/L; \>=5.6 mmol/L.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'number analyzed' = participants with available data for each specified category.

Criteria for potentially clinically significant abnormalities: * Creatinine: \>=150 micromol/L (adults); \>=30% change from baseline, \>=100% change from baseline. * Creatinine clearance: \<15 mL/min; \>=15 to \<30 mL/min; \>=30 to \<60 mL/min; \>=60 to \<90 mL/min. * Blood urea nitrogen: \>=17 mmol/L. * Uric acid: \<120 micromol/L; \>408 micromol/L.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria with potentially clinically significant urine abnormalities: pH: \<= 4.6; pH: \>= 8.0.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Criteria for potentially clinically significant ECG abnormalities: * HR: \<50 bpm; \<50 bpm and DFB \>=20 bpm; \<40 bpm; \<40 bpm and DFB \>=20 bpm; \<30 bpm; \<30 bpm and DFB \>=20 bpm; \>90 bpm; \>=90 bpm and IFB \>=20 bpm; \>100 bpm; \>=100 bpm and IFB \>=20 bpm; \>120 bpm; \>=120 bpm and IFB \>=20 bpm. * PR Interval: \>200 ms; \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB \>=25%. * QRS Interval: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25%. * QT Interval: \>500 ms. * QTc B: \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms. * QTc F: \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'overall number analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Criteria for potentially clinically significant vital sign abnormalities: SBP supine: \<=95 mmHg and DFB \>=20 mmHg; \>=160 mmHg and IFB \>=20 mmHg. DBP supine: \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg. SBP (Orthostatic): \<=-20 mmHg. DBP (Orthostatic): \<=-10 mmHg. HR supine: \<=50 bpm and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm. Weight: \>=5% DFB; \>=5% IFB.

Time frame: From end of Week 24 (Baseline of OLE Period) up to Week 300

Population: Analysis was performed on safety population (OLE Period). Here, 'number analyzed' = participants with available data for each specified category.

AE was defined as any untoward medical occurrence in participant who received IMP and did not necessarily had to have causal relationship with treatment. All reported AEs are TEAEs developed/worsened during 'on treatment period' (from end of week 24 \[Baseline of OLE Period\] up to last dose in OLE period + 6 weeks \[follow-up\], regardless of unplanned intermittent discontinuations). SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event.

Time frame: From end of Week 24 (Baseline of OLE Period) up to last dose in OLE + 6 weeks of follow up (i.e. up to Week 306)

Population: Analysis was performed on safety population (OLE period) which included all randomized participants who continued OLE period and received at least one dose of the study medication during OLE period, analyzed according to the treatment they have actually received.

Time frame: Pre-dose at Week 24 (Baseline of OLE period), 36, 48, 60, 84, 108, 132, 156, 180, 204, 228, 252, 276, 300 and 306

Population: Analysis was performed on Pharmacokinetics population (OLE period) which consisted of all participants from the randomized population who received at least 1 dose of IMP with at least one post-dose, non-missing serum sarilumab concentration. Here, 'number analyzed' = participants with available data for each specified category and '0' denotes that no participant was available for the assessment at the specified timepoint.