Methotrexate (Rheumatrex) High Dose Special Investigation (Regulatory Post Marketing Commitment Plan)

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.

Time frame: Baseline and 24 Weeks

Population: 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.

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.

Time frame: Baseline and 24 Weeks

Population: 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. 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.

Time frame: Baseline and 24 Weeks

Population: 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. 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.

Time frame: Baseline and 24 Weeks

Population: 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.

A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate.

Time frame: 24 Weeks

Population: 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.

Time frame: 24 Weeks

Population: 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.

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.

Time frame: 24 Weeks

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

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.

Time frame: 24 Weeks

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