Table 2.
RA-related biologic therapy and clinical trials.
| Name | Target | ClinicalTrials.gov ID | Primary Outcome | Pharmacological Role | Ref. |
|---|---|---|---|---|---|
| Tocilizumab | IL-6R | NCT01951170 | Change From Baseline in Genant-modified Total Sharp Score (mTSS) [Time Frame: From baseline to Week 24] | Inhibiting IL-6R | (195) |
| Rituximab | B cell | NCT02304354 | DAS28 and T-lymphocyte count [Time Frame: up to week 48] | Primarily depletion of B cells, in addition to reduction of T cells and macrophages | (196) |
| NCT01592292 | (1) Mean Change From Baseline in DAS28 at Month 6 in Intention to Treat (ITT) Population [Time Frame: Baseline and Month 6] | Depletion of B cells | |||
| |||||
| NCT02079532 | Change From Baseline to Week 24 in DAS28 [Time Frame: Week 24] | Depletion of B cells | |||
| NCT01071798 | DAS28 Score and HAQ Disability Index (HAQ-DI) [Time Frame: at baseline of each cycle and approximately 15 days, 6 weeks (only cycle 1), 12 weeks (3 months), 18 weeks (only cycle 1), and 24 weeks (6 months) after the start of the respective cycle] | Predicting biomarkers of clinical therapy | (197) | ||
| NCT01126541 | DAS28-CRP Area Under the Curve (AUC) at Week 104 [Time Frame: Week 104] | Predicting biomarkers of clinical therapy | (198–201) | ||
| NCT00468546 | Number of Participants With ACR 20 Response at Week 24 [Time Frame: Week 24] | Predicting biomarkers of clinical therapy | (202) | ||
| NCT00147966 | ACR 20 Response at Week 12 [Time Frame: 0 and 12 weeks] | Predicting biomarkers of clinical therapy | (74) | ||
| Infliximab | TNF-α | NCT00908089 | Remission by ACR criteria [Time Frame: 2 years] | Inhibiting inflammation | (203) |
| Infliximab | TNF-α | NCT00213564 | NA | Response factor prediction | |
| Infliximab | TNF-α、T cell、B cell、IL-6R | NCT01638715 | Absolute Change in the Simplified Disease Activity Index (SDAI) [Time Frame: 24 Weeks] | Response factor prediction | |
| Tocilizumab | |||||
| Abatacept | |||||
| rituximab | |||||
| Adalimumab | TNF-α | NCT00195663 | (1) Number of Participants Meeting ACR50 Response Criteria at Week 52 [Time Frame: Baseline and 52 Weeks] | Inhibiting inflammation | (204) |
| (2) Change From Baseline in mTSS at Week 52 [Time Frame: Baseline and Week 52] | |||||
| Tabalumab | BAFF | NCT00689728 | Percentage of Participants ACR 50 Response at Week 16 [Time Frame: 16 weeks] | Decreasing the number of autoimmune B cells | (205) |
| Spebrutinib(CC-292) | Bruton’s tyrosine kinase (BTK) | NCT01975610 | ACR 20 Response [Time Frame: Week 4] | Inhibiting B cell proliferation and osteoclast production | |
| Tofacitinib | JAK1/3 | NCT00976599 | (1) Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28 [Time Frame: Day -7 (Baseline), Day 28] | Inhibiting angiogenesis and reducing P-STAT1, P-STAT3 | (206) |
| (2) Change From Baseline in Protein Expression of TNF-α, IL-6, IL-17a, and IL-10 at Day 28 [Time Frame: Baseline (Day -7), Day 28] … etc. (82 items in total) | |||||
| Ustekinumab | IL-12/IL-23 | NCT01645280 | Percentage of Participants With ACR 20 Response at Week 28 [Time Frame: Week 28] | Inhibiting IL-12/IL-23 | (207) |
| Anakinra | IL-1R | NCT00117091 | Percentage of subjects continuing Kineret® therapy at the end of the study (i.e., responders according to pre-defined response assessment criteria) | Inhibiting IL-1R | |
| KB003 | GM-CSF | NCT00995449 | This Study Was Initiated With a Safety run-in Period to Evaluate Acceptability of Repeat-dose Safety. [Time Frame: Weeks 14 and 30] | Inhibiting M1 macrophage polarization | |
| MOR103 (GSK3196165/Otilimab) | GM-CSF | NCT01023256 | Percentage of Patients With Treatment-emergent or Serious Adverse Events [Time Frame: From the first dose through the 16-week visit] | Inhibiting M1 macrophage polarization | (208) |
| NCT02799472 | (1) Change From Baseline in Target Engagement Biomarkers- Soluble GM-CSF Complexed to GSK3196165 [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22)] | ||||
| (2) Change From Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 CBP A8 and A9 [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)] … etc., 19 items in total | |||||
| NCT02504671 | Percentage of Participants with DAS28-CRP Remission (DAS28 <2.6) at Week 24 [Time Frame: Week 24] | ||||
| NCT03980483 | Proportion of participants achieving ACR 20 at Week 12: superiority comparison with placebo [Time Frame: Week 12] | ||||
| NCT03970837 | Proportion of participants achieving 20% improvement in ACR20 at Week 12: superiority comparison with placebo [Time Frame: Week 12] | ||||
| NCT04333147 | (1) Incidence of adverse events (AEs), serious AEs (SAEs) and AEs of special interests (AESI) [Time Frame: Up to 4 years] | ||||
| (2) Change from Baseline in platelet count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils (Giga cells per liter [giga cells/L]) [Time Frame: Baseline (Day 1) and up to 4 years] … etc. (eight items in total) | |||||
| NCT04134728 | Proportion of participants achieving 20% improvement in ACR20 at Week 12 superiority comparison with placebo [Time Frame: Week 12] | ||||
| NCT03028467 | (1) Maximum Observed Concentration (Cmax) of GSK3196165 [Time Frame: Pre-dose on Days 1, 8, 15, 29, 57, and 71; anytime during visit on Days 3, 74, 85, 106, 127, and 155] | ||||
| (2) AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]), AUC From Time Zero Extrapolated to Infinity (AUC [0-inf]), AUC Over the Dosing Interval (AUCtau) of GSK3196165 [Time Frame: Pre-dose on Days 1, 8, 15, 29, 57, and 71; anytime during visit on Days 3, 74, 85, 106, 127, and 155] | |||||
| (3) Time to Reach Cmax (Tmax) and Terminal Half-life (t1/2) f GSK3196165 [Time Frame: Pre-dose on Days 1, 8, 15, 29, 57, and 71; anytime during visit on Days 3, 74, 85, 106, 127, and 155] | |||||
| (4) Number of Participants With Any AE, SAE, and Adverse Events of Special Interest (AESI) [Time Frame: Up to 22 weeks] | |||||
| NCT03285191 | Number of subjects with RA participating in CE interviews [Time Frame: 1 day] | ||||
| MORAb-022 | GM-CSF | NCT01357759 | Safety measures to include adverse events, clinical laboratory results, vital signs, ECGs, physical examinations, local tolerability at the infusion site single escalating intravenous (IV) doses of MORAb-022 in healthy subjects and subjects with RA [Time Frame: Approximately 113 days] | Inhibiting M1 macrophage polarization | |
| Namilumab (AMG203) | GM-CSF | NCT01317797 | (1) Number of Participants for Clinically Significant Clinical Laboratory Results, Clinically Significant Electrocardiogram (ECG) Findings, Clinically Significant Vital Signs, Clinically Significant Pulmonary Function Tests, and Clinically Significant Physical Examination Findings [Time Frame: From Day 1 Up to Day 118] | Inhibiting M1 macrophage polarization | (209, 210) |
| (2) Number of Participants Reporting One or More Treatment Emergent Adverse Events [Time Frame: From Day 1 Up to Day 118] | |||||
| NCT02393378 | Change From Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24 [Time Frame: Baseline and Week 24] | ||||
| NCT02379091 | Change From Baseline in DAS28-CRP at Week 12 [Time Frame: Baseline and Week 12] | ||||
| Mavrilimumab | GM-CSFRα | NCT00771420 | Incidence and severity of adverse events • Changes in vital signs, ECG, lung function tests and clinical laboratory values [Time Frame: End of study] | Inhibiting M1 macrophage polarization | (211–216) |
| NCT01050998 | (1) Percentage of Participants Who Achieved DAS28-CRP Response at Day 85 [Time Frame: Day 85] | ||||
| (2) Percentage of Participants Who Achieved DAS28-CRP Response at Day 85 by Region [Time Frame: Day 85] … etc. (24 items in total) | |||||
| NCT01706926 | (1) Change From Baseline in DAS28-CRP Score at Day 85 [Time Frame: Baseline and Day 85] | ||||
| (2) Percentage of Participants Who Achieved ACR20 Responses at Day 169 [Time Frame: Day 169] | |||||
| NCT01715896 | (1) Percentage of Participants Who Achieved ACR20 Responses, ACR50 Responses, and ACR70 Responses at Day 169 [Time Frame: Day 169] | ||||
| (2) Percentage of Participants Who Achieved DAS28-CRP Response at Day 169 [Time Frame: Day 169] | |||||
| (3) Percentage of Participants Who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score Improvement From Baseline and ≥0.25 at Day 169 [Time Frame: Day 169] | |||||
| NCT01712399 | (1) Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [Time Frame: From the start of drug administration up to 12 weeks after the last dose for the study (approximately up to 3 years)] | ||||
| (2) Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs [Time Frame: From the start of drug administration in the study up to 12 weeks after the last dose (approximately up to 3 years)] … etc. (10 items in total) |
*NA, Not applicable