Table 1.
Overview of phase III studies with tocilizumab IV and SC, and sarilumab SC, on individual clinical endpoints
| Study population | Treatment arms | ACR response | CRP | ESR | DAS28-CRP | DAS28-ESR | CDAI | Radiographic outcomes | |
|---|---|---|---|---|---|---|---|---|---|
| Sarilumab combination studies | |||||||||
| MOBILITY [39] | MTX-IR (n = 1197) |
S 150 mg SC S 200 mg SC Placebo SC Q2W 52 weeks |
Co-primary endpoint: ACR20 W24 Secondary endpoint: ACR50, ACR70 W24, W52 |
Secondary endpoint | Not reported | Secondary endpoints: proportion with DAS28-CRP ≤ 2.6 W24, W52; change from baseline in DAS28-CRP W24, W52 | Not reported | Secondary endpoints: change from baseline W24, W52; proportion with CDAI remission ≤ 2.8 W24, W52 |
Co-primary endpoint: vdH-mTSS W52 Secondary endpoints: erosion and JSN score change W24, W52 vdH-mTSS W24 |
| https://clinicaltrials.gov/ct2/show/NCT01061736 | Patients also received MTX | ||||||||
| TARGET [40] | TNF-IR (n = 546) |
S 150 mg SC S 200 mg SC Placebo SC Q2W 24 weeks |
Co-primary endpoint: ACR20 W24 Secondary endpoints: ACR50, ACR70 W24 |
Secondary endpoint: change from baseline W12, W24 | Not reported | Secondary endpoints: change from baseline W24; proportion with DAS28-CRP < 2.6 W24 | Not reported | Secondary endpoint: change from baseline in CDAI W24 | Not reported |
| https://clinicaltrials.gov/ct2/show/NCT01709578 | Patients also received csDMARDs | ||||||||
| Sarilumab monotherapy studies | |||||||||
| MONARCH [41] | MTX-IR (n = 369) |
S 200 mg SC A 40 mg SC Placebo SC Q2W 24 weeks |
Secondary endpoints: ACR20, ACR50, ACR70 W24 | Secondary endpoint: change from baseline W24 | Secondary endpoint: change from baseline W24 | Secondary endpoints: proportion with DAS28-CRP ≤ 2.8 and ≤ 3.3 W24; change from baseline in DAS28-CRP W24 |
Primary endpoint: change from baseline W24 Secondary endpoint: proportion with DAS28-ESR < 2.6 W24 |
Secondary endpoint: change from baseline W24 proportion with CDAI remission ≤ 2.8 W24 | Not reported |
| https://clinicaltrials.gov/ct2/show/NCT02332590 | |||||||||
| SC tocilizumab combination studies | |||||||||
| SUMMACTA [42] | csDMARD-IR (n = 1262) |
T 162 mg SC QW T 8 mg/kg IV Q4W 24 weeks |
Primary endpoint: ACR20 W24 Secondary endpoints: ACR50, ACR70 W24; ACR20, ACR50, ACR70 W97 |
Not reported | Not reported | Not reported | Secondary endpoint: proportion with < 2.6 W24, W97 | Additional endpoint of CDAI remission ≤ 2.8 W24 | Not reported |
| https://clinicaltrials.gov/ct2/show/NCT01194414 | |||||||||
| BREVACTA [43] | csDMARD-IR (n = 656) |
T 162 mg SC Placebo SC Q2W 24 weeks |
Primary endpoint: ACR20 W24 Secondary endpoints: ACR50, ACR70 W24 |
Secondary endpoint: change from baseline W24 | Secondary endpoint: change from baseline W24 | Not reported | Secondary endpoint: change from baseline W24; proportion with < 2.6 W24; proportion with ≤ 3.2 W24 | Not reported | Secondary endpoint: change from baseline in vdH-mTSS W24 |
| https://clinicaltrials.gov/ct2/show/NCT01232569 | |||||||||
| IV tocilizumab combination studies | |||||||||
| LITHE [44] | MTX-IR (n = 1196) |
T 4 mg/kg IV T 8 mg/kg IV Placebo IV Q4W 52 weeks |
Co-primary endpoint: ACR20 W24 Secondary endpoints: ACR20 W52; ACR50/70 W24, W52, W104 |
Secondary endpoint: change from baseline W24, W52, W104 | Secondary endpoint: change from baseline W24, W52, W104 | Not reported | Secondary endpoints: change in DAS28-ESR W24, W52, W104; proportion with DAS28 ≤ 3.2 and DAS28 < 2.6, W24, W52, W104 | Not reported |
Co-primary endpoint: change from baseline in total G-mTSS W52, W104 Secondary endpoints: change from baseline in erosion and JSN W24, W52, G-mTSS W24; proportion with no progression of the total erosion or JSN W24 |
| https://clinicaltrials.gov/ct2/show/NCT00106535 | Patients also receive MTX | ||||||||
| OPTION [45] | csDMARD-IR (n = 623) |
T 8 mg/kg IV T 4 mg/kg IV Placebo IV Q4W 24 weeks |
Primary endpoint: ACR20 W24 Secondary endpoints: ACR50, ACR70 W24 |
Laboratory measure: change from baseline W24 | Laboratory measure: change from baseline W24 | Secondary endpoint: change from baseline W24; proportion with DAS28 < 2.6 W24 | Not reported | Not reported | |
| https://clinicaltrials.gov/ct2/show/NCT00106548 | Patients also receive MTX | ||||||||
| TOWARD [46] | csDMARD-IR (n = 1220) |
T 8 mg/kg IV Placebo IV Q4W 24 weeks |
Primary endpoint: ACR20 W24 Secondary endpoints: ACR50, ACR70 W24 |
Additional endpoint: change from baseline W24 | Additional endpoint: change from baseline W24 | Not reported | Additional endpoint: DAS28-ESR W24 | Not reported | Not reported |
| https://clinicaltrials.gov/ct2/show/NCT00106574 | Patients also receive csDMARDs | ||||||||
| RADIATE [47] | TNF-IR (n = 499) |
T 8 mg/kg IV T 4 mg/kg IV Placebo IV Q4W 24 weeks |
Primary endpoint: ACR20 W24 Secondary endpoints: ACR50, ACR70 W24 | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported |
| https://clinicaltrials.gov/ct2/show/NCT00106522 | Patients also receive MTX | ||||||||
| IV tocilizumab monotherapy studies | |||||||||
| U-ACT-EARLY [48] | Newly diagnosed DMARD-naïve (n = 317) |
T 8 mg/kg IV + MTX Q4W 104 weeks |
Secondary endpoints: ACR20, ACR50, ACR70 W12, W24, W52, W104 | Secondary endpoint: change from baseline at W12, W24, W52, W104 | Not reported | Secondary endpoint: DAS28-CRP W24, W52, W104 |
Primary endpoint: proportion with < 2.6 sustained Secondary endpoint: DAS28-ESR W24, W52, W104 |
Secondary endpoint: change from baseline W24, W52, W104 | Secondary endpoint: change from baseline in vdH-mTSS W52, W104 |
| https://clinicaltrials.gov/ct2/show/NCT01034137 | |||||||||
| FUNCTION [49] | MTX-naïve patients with early progressive RA (n = 1162) |
T 8 mg/kg IV T 8 mg/kg IV + MTX T 4 mg/kg + MTX Q4W 104 weeks |
Secondary endpoints: ACR20, ACR50, ACR70 W24 and W52 | Not reported | Not reported | Not reported |
Primary endpoint: proportion with < 2.6 W24 Secondary endpoint: proportion with < 2.6 W52 |
CDAI remission (< 2.8) | Secondary endpoints: change from baseline vdH-mTSS W52, change from baseline vdH erosion score W52, change from baseline JSN W52, proportion with no progression W52, W104 |
| https://clinicaltrials.gov/ct2/show/NCT01007435 | |||||||||
| ACT-RAY [50] | MTX-IR (n = 556) |
T 8 mg/kg IV + MTX T 8 mg/kg IV 104 weeks |
Secondary endpoints: ACR20, ACR50, ACR70, ACR90 W24, W52, W104 (and time to each) | Secondary endpoint: change from baseline W24, W52 | Secondary endpoint: change from baseline W24, W52 | Not reported |
Primary endpoint: proportion with < 2.6 W24 Secondary endpoint: proportion with < 3.2 W24 change from baseline W24, W52 |
Not reported | Secondary endpoint: change from baseline G-mTSS W24, W52, W104 |
| https://clinicaltrials.gov/ct2/show/NCT00810199 | |||||||||
| ADACTA [51] | MTX-INT (n = 326) |
T 8 mg/kg IV Q4W A 40 mg SC Q2W 24 weeks |
Secondary endpoints: ACR20, ACR50, ACR70 W24 | Not reported | Not reported | Not reported |
Primary endpoint: change from baseline W24 Secondary endpoint: proportion with ≤ 3.2 and < 2.6 W24 |
Not reported | Not reported |
| https://clinicaltrials.gov/ct2/show/NCT01119859 | |||||||||
A adalimumab, ACR20/50/70/90 American College of Rheumatology 20%/50%/70%/90% response, CDAI Clinical Disease Activity Index, CRP C-reactive protein, csDMARD conventional synthetic disease-modifying antirheumatic drug, DAS28 28-Joint Disease Activity Score, DMARD disease-modifying antirheumatic drug, ESR erythrocyte sedimentation rate, G-mTSS Genant-modified Total Sharp Score, INT intolerant, IR inadequate response, IV intravenous, JSN joint space narrowing, mTSS modified Total Sharp Score, MTX methotrexate, n number of patients, Q2W every 2 weeks, Q4W every 4 weeks, QW weekly, RA rheumatoid arthritis, S sarilumab, SC subcutaneous, T tocilizumab, TNF tumor necrosis factor, vdH van der Heijde, vdH-mTSS van der Heijde-modified Total Sharp Score, W week