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| Name | Class |
|---|---|
| Monash University | OTHER |
| Beijing ShuangLu Pharmaceutical Co., Ltd. | OTHER |
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Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, characterized by symmetric poly-arthritis usually involving the small joints of the hands and feet. In addition, various extra-joint manifestations may develop. Several immunomodulating agents have been attempted in the treatment of RA without achieving satisfactory results. Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). The investigators hypothesized that low-dose IL-2 could be a novel therapy in active RA patients. This clinical study will test the efficacy and safety of low dose IL-2 treatment in RA. The investigators perform a single-centre, double-blind pilot trial with hrIL-2 in RA. The investigators evaluate the effectiveness and safeness of low-dose hrIL-2 for RA by randomized controlled study (hrIL-2 (N = 23) + Methotrexate (MTX)+ Loxoprofen versus placebo+MTX + Loxoprofen group (N = 24)).
Each RA patients (n=47) with DAS>3.2 received low-dose IL-2+MTX+ Loxoprofen or placebo+MTX + Loxoprofen (active group: placebo group =1:1, 1 million units every other day subcutaneously (hrIL-2 1×106, ip, Qod) for a period of 14 days. After a 14-day rest, another cycle started) for 3 cycles. The end points were safety and clinical and immunologic response.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental | Active Comparator | hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen |
|
| Placebo Comparator | Placebo Comparator | hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| hrIL-2 active | Drug | hrIL-2 active (1 million U doses of hrIL-2s.c.injection) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving DAS28 Remission. | DAS 28 remission is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 | week 24 |
| Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria | The assessments are based on a 20% or greater improvement from Baseline in the number of tender joints, a 20%, or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | week 12, week 24 |
| The Change From Baseline of Clinical Disease Activity Index (CDAI) | Clinical Disease Activity Index(CDAI), the minimum is 0, the maximum is 76. higher scores mean a worse outcome. The change of from baseline of CDAI, the minimum is -76, the maximum is 76. higher scores mean a worse outcome. | week 12, week 24 |
| The Change From Baseline of Simplified Disease Activity Index (SDAI) | Simplified Disease Activity Index(SDAI). the minimum is 0, the maximum is 96. higher scores mean worse outcome. The change from baseline of SDAI. the minimum is -96, the maximum is 96. higher scores mean worse outcome. | week 12, week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event, drug-induced liver and kidney damage. | Up to week 24 |
| Percentage of CD4+ Treg Cells |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Zhanguo Li, MD PhD | Peking University Institute of Rheuamotology and Immunology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Rheumatology and Immunology, Peking University People's Hospital | Beijing | Beijing Municipality | 100044 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35250032 | Derived | Zhang X, Miao M, Zhang R, Liu X, Zhao X, Shao M, Liu T, Jin Y, Chen J, Liu H, Zhang X, Li Y, Zhou Y, Yang Y, Li R, Yao H, Liu Y, Li C, Li Y, Ren L, Su Y, Sun X, He J, Li Z. Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2022 Mar 7;7(1):67. doi: 10.1038/s41392-022-00887-2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental | hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration) |
| FG001 | Placebo Comparator | hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental | hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration) |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Achieving DAS28 Remission. | DAS 28 remission is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6 | Posted | Count of Participants | Participants | week 24 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental | hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalized not related to RA | Surgical and medical procedures | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| gastrointestinal disorders | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Zhanguo Li | Peking university People's Hospital | +86-13810001444 | 13810001444@163.com |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D005492 | Folic Acid |
| C040656 | loxoprofen |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| hrIL-2 placebo | Drug | hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) |
|
|
| MTX | Drug | Methotrexate (oral administration) |
|
| Folic Acid | Drug | Folic Acid (oral administration) |
|
| Loxoprofen | Drug | Loxoprofen (oral administration) |
|
analysis regulatory CD4+ T(Treg) cells before and during IL-2 treatment. P values<0.05 are considered statistically significant.
| week 12, week 24 |
| Percentage of Participants Achieving DAS28 Low Disease Activity. | Low disease activity is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 3.2 | week 12, week 24 |
| Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response | Good response is defined as: DAS28-ESR ≤ 3.2 and decrease from Baseline by > 1.2. moderate response is defined as achievement of one of the following: DAS28-ESR ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2 DAS28-ESR > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6 DAS28-ESR > 5.1 and decrease from Baseline >1.2. | week 12, week 24 |
| Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria | The assessments are based on a 50% or greater improvement from Baseline in the number of tender joints, a 50%, or more improvement in the number of swollen joints, and a 50% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | week 12, week 24 |
| Percentage of Participants Meeting the American College of Rheumatology 70% Response Criteria | The assessments are based on a 70% or greater improvement from Baseline in the number of tender joints, a 70%, or more improvement in the number of swollen joints, and a 70% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | week 12, week 24 |
| Percentage of Participants Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice | The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1. | week 12, week 24 |
| The Change From Baseline of a Health Assessment Questionnaire- Disability Index (HAQ-DI) | The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. The total score ranges from 0 to 3 with lower scores meaning lower disability. The change from baseline of HAQ-DI, minimum is -3, the maximum is 3. higher scores mean a worse outcome. | week 12, week 24 |
| The Scores of SF-36 Quetionnaire | Score ranging from 0 to 100 with higher scores a better outcome. | week 12, week 24 |
| Work Productivity Survey - Rheumatoid Arthritis [WPS-RA] | The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).higher scores mean a worse outcome. | week 24 |
| Erythrocyte Sedimentation Rate (ESR) | week 12, week 24 |
| C Reactive Protein (CRP) | week 12, week 24 |
| The Change From Baseline of Patient's Global Assessment of Disease Activity (PtGADA) | VAS score from 0 to 100 for Patient's Global Assessment of Disease Activity Higher scores mean a worse outcome. The change from baseline of PtGADA, the minimum is -100, the maximum is 100. Higher scores mean a worse outcome. | week 12, week 24 |
| The Change From Baseline of Physician's Global Assessment of Disease Activity (PhGADA) | VAS score from 0 to 100 for Physician's Global Assessment of Disease Activity higher scores mean a worse outcome. The change from baseline, the minimum is -100, the maximum is 100. | week 12, week 24 |
| The Change From Baseline of Patient's Assessment of Arthritis Pain (PtAAP) | VAS score from 0 to 100 for Patient's Assessment of Arthritis Pain higher scores mean a worse outcome. The change from baseline of PtAAP, the minimum is -100, the maximum is 100. | week 12, week 24 |
| Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]-2 | In the last month, number of work days missed, number of work days with reduced productivity. In the last month, number of days with no household work, number of days with reduced household work productivity, number of days with hired outside help, number of days missed of family/social/leisure activities in the last month.higher scores mean a worse outcome. | week 24 |
| Placebo Comparator |
hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants | No |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
|
|
|
| Primary | Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria | The assessments are based on a 20% or greater improvement from Baseline in the number of tender joints, a 20%, or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Posted | Count of Participants | Participants | week 12, week 24 |
|
|
|
|
| Primary | The Change From Baseline of Clinical Disease Activity Index (CDAI) | Clinical Disease Activity Index(CDAI), the minimum is 0, the maximum is 76. higher scores mean a worse outcome. The change of from baseline of CDAI, the minimum is -76, the maximum is 76. higher scores mean a worse outcome. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
|
|
|
|
| Primary | The Change From Baseline of Simplified Disease Activity Index (SDAI) | Simplified Disease Activity Index(SDAI). the minimum is 0, the maximum is 96. higher scores mean worse outcome. The change from baseline of SDAI. the minimum is -96, the maximum is 96. higher scores mean worse outcome. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
|
|
|
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| Secondary | Number of Participants With Adverse Events | adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event, drug-induced liver and kidney damage. | Posted | Count of Participants | Participants | Up to week 24 |
|
|
|
|
| Secondary | Percentage of CD4+ Treg Cells | analysis regulatory CD4+ T(Treg) cells before and during IL-2 treatment. P values<0.05 are considered statistically significant. | Posted | Mean | Full Range | percentage of CD4+ T cells | week 12, week 24 |
|
|
|
|
| Secondary | Percentage of Participants Achieving DAS28 Low Disease Activity. | Low disease activity is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 3.2 | Posted | Count of Participants | Participants | week 12, week 24 |
|
|
|
|
| Secondary | Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response | Good response is defined as: DAS28-ESR ≤ 3.2 and decrease from Baseline by > 1.2. moderate response is defined as achievement of one of the following: DAS28-ESR ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2 DAS28-ESR > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6 DAS28-ESR > 5.1 and decrease from Baseline >1.2. | Posted | Count of Participants | Participants | week 12, week 24 |
|
|
|
|
| Secondary | Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria | The assessments are based on a 50% or greater improvement from Baseline in the number of tender joints, a 50%, or more improvement in the number of swollen joints, and a 50% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Posted | Count of Participants | Participants | week 12, week 24 |
|
|
|
|
| Secondary | Percentage of Participants Meeting the American College of Rheumatology 70% Response Criteria | The assessments are based on a 70% or greater improvement from Baseline in the number of tender joints, a 70%, or more improvement in the number of swollen joints, and a 70% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Posted | Count of Participants | Participants | week 12, week 24 |
|
|
|
|
| Secondary | Percentage of Participants Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice | The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1. | Posted | Count of Participants | Participants | week 12, week 24 |
|
|
|
|
| Secondary | The Change From Baseline of a Health Assessment Questionnaire- Disability Index (HAQ-DI) | The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. The total score ranges from 0 to 3 with lower scores meaning lower disability. The change from baseline of HAQ-DI, minimum is -3, the maximum is 3. higher scores mean a worse outcome. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
|
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|
|
| Secondary | The Scores of SF-36 Quetionnaire | Score ranging from 0 to 100 with higher scores a better outcome. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
|
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|
|
| Secondary | Work Productivity Survey - Rheumatoid Arthritis [WPS-RA] | The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).higher scores mean a worse outcome. | Posted | Median | Inter-Quartile Range | units on a scale | week 24 |
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| Secondary | Erythrocyte Sedimentation Rate (ESR) | Posted | Mean | Standard Deviation | millimeter/hour | week 12, week 24 |
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| Secondary | C Reactive Protein (CRP) | Posted | Mean | Standard Deviation | mg/L | week 12, week 24 |
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| Secondary | The Change From Baseline of Patient's Global Assessment of Disease Activity (PtGADA) | VAS score from 0 to 100 for Patient's Global Assessment of Disease Activity Higher scores mean a worse outcome. The change from baseline of PtGADA, the minimum is -100, the maximum is 100. Higher scores mean a worse outcome. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
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| Secondary | The Change From Baseline of Physician's Global Assessment of Disease Activity (PhGADA) | VAS score from 0 to 100 for Physician's Global Assessment of Disease Activity higher scores mean a worse outcome. The change from baseline, the minimum is -100, the maximum is 100. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
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| Secondary | The Change From Baseline of Patient's Assessment of Arthritis Pain (PtAAP) | VAS score from 0 to 100 for Patient's Assessment of Arthritis Pain higher scores mean a worse outcome. The change from baseline of PtAAP, the minimum is -100, the maximum is 100. | Posted | Median | Inter-Quartile Range | score on a scale | week 12, week 24 |
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| Secondary | Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]-2 | In the last month, number of work days missed, number of work days with reduced productivity. In the last month, number of days with no household work, number of days with reduced household work productivity, number of days with hired outside help, number of days missed of family/social/leisure activities in the last month.higher scores mean a worse outcome. | Posted | Median | Inter-Quartile Range | days | week 24 |
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|
|
| 11 |
| 23 |
| 2 |
| 23 |
| 9 |
| 23 |
| EG001 | Placebo Comparator | hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration) | 9 | 24 | 1 | 24 | 8 | 24 |
| Hepatic enzyme increased | Hepatobiliary disorders | Non-systematic Assessment |
|
| Injection site reactions | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | Non-systematic Assessment |
|
| Fever after injection | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Worsening of RA | Immune system disorders | Non-systematic Assessment |
|
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| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006571 | Heterocyclic Compounds |
| Household work days missed due to arthritis |
|
| Days with household work productivity reduced |
|
| Days with activities missed due to arthritis |
|
| Days with outside help hired due to arthritis |
|