Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 [CRP]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. Mean change from baseline in the DAS28-4 (CRP) at Week 24 is calculated. The total scale range can not be specified.

Pre-specified important adverse events were 1) Interstitial pneumonia, 2) Pulmonary fibrosis, 3) Hepatic impairment, 4) Renal impairment, 5) Hematopoietic disorder, 6) Infection, and 7) Lymphoma. A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.

Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assesable effectiveness analysis population, was presented along with the corresponding 2-sided 95% CI. Clinical effectiveness of methotrexate was assessed as "effective" or "ineffective" by the investigator. The assessment was based on the baseline condition of disease control and degree of alleviation from baseline in clinical symptoms and laboratory data.

Stage was classified into four-grade based on below criteria by doctor at beginning. StageI:No radiological finding of osteolysis. StageII:1.Radiological finding of osteoporosis with or without mild fracture of subchondral bone. There may be mild cartilage destruction.

2. Articular movement may be restricted, but no joint deformity StageIII:1.Osteoporosis and radiological finding of bone and cartilage destruction 2.Joint deformity such as subluxation, ulnar malposition or extension is present. There is no fibrous or osseous ankylosis.

StageIV:Fibrous or osseous ankylosis is present.

Class was classified into four-grade based on below criteria by doctor at beginning.

Class1:Complete ability to carry out all the usual duties without handicaps Class2:Adequate for normal activities despite handicap of discomfort or limited motion of one of the joints Class3:Limited to little or none of the duties of usual occupation or self-care Class4:Incapacitated, largely or wholly bed-ridden or confined to a wheelchair with little or no self-care

Disease activity score based on 28-joint count and erythrocyte sedimentation rate (4 variables) (DAS28-4 [ESR]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, ESR (mm/hour) and visual analogue scale (VAS) of general health assessed by participant or investigator. Higher score indicated more disease activity. The total scale range of DAS28-4 (ESR) , minimum is 0.0 and maximum can not be specified. DAS28-4 (ESR) >5.1 indicated high disease activity, ?3.2 to ?5.1 indicated moderate disease activity, <3.2 indicated low disease activity, and <2.6 indicated remission.

The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (ESR) at least once. Participants with observed DAS28-4(ESR) were included in table.

Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 [CRP]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. The total scale range of DAS28-4 (ESR) , minimum is 0.0 and maximum can not be specified. DAS28-4 (CRP) >4.1 indicated high disease activity, ≥2.7 to 4.1 indicated moderate disease activity, <2.7 indicated low disease activity, and <2.3 indicated remission.

The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (CRP) at least once. Participants with observed DAS28-4(CRP) were included in table.

Disease activity score based on 28-joint count and erythrocyte sedimentation rate (4 variables) (DAS28-4 [ESR]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, ESR (mm/hour) and visual analogue scale (VAS) of general health assessed by participant or investigator. Mean change from baseline in the DAS28-4 (ESR) at Week 24 is calculated. The total scale range can not be specified.

The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (ESR) at least once. Participants with observed change in DAS28-4(ESR) were included in table.

Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 [CRP]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. Mean change from baseline in the DAS28-4 (CRP) at Week 24 is calculated. The total scale range can not be specified.

The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (CRP) at least once. Participants with observed change in DAS28-4 (CRP) were included in table.

A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.

The safety analysis set comprised of participants who satisfied the inclusion criteria and had received methotrexate at least once.

Pre-specified important adverse events were 1) Interstitial pneumonia, 2) Pulmonary fibrosis, 3) Hepatic impairment, 4) Renal impairment, 5) Hematopoietic disorder, 6) Infection, and 7) Lymphoma. A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.

The safety analysis set comprised of participants who satisfied the inclusion criteria and had received methotrexate at least once.

Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assesable effectiveness analysis population, was presented along with the corresponding 2-sided 95% CI. Clinical effectiveness of methotrexate was assessed as "effective" or "ineffective" by the investigator. The assessment was based on the baseline condition of disease control and degree of alleviation from baseline in clinical symptoms and laboratory data.

The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (clinical efficacy rate) at least once. Participants with observed effectiveness data were included in table.