Table 3.
Overview of phase III studies with tocilizumab IV and SC, and sarilumab SC, on individual patient-reported outcome endpoints
| Study population | Treatment arms | HAQ-DI | SF-36 | Fatigue | Pain | Morning stiffness | |
|---|---|---|---|---|---|---|---|
| Sarilumab combination studies | |||||||
| MOBILITY | MTX-IR (n = 1197) |
S 150 mg SC S 200 mg SC Placebo SC Q2W 52 weeks |
Co-primary endpoint: change from baseline W16 | Not reported | Not reported | Secondary endpoint: change from baseline VAS W24 | Not reported |
| [39] https://clinicaltrials.gov/ct2/show/NCT01061736 | Patients also received MTX | ||||||
| TARGET | TNF-IR (n = 546) |
S 150 mg SC S 200 mg SC Placebo SC Q2W 24 weeks |
Co-primary endpoint: change from baseline W12 Secondary endpoint: change from baseline W24 |
Secondary endpoints: change from baseline SF-36 physical W24; change from baseline SF-36 mental W24 | Secondary endpoints: change from baseline FACIT-F W24; also measured in RAID domain (change from baseline W12, W24) | Secondary endpoints: change from baseline VAS W24; also measured in RAID domain (change from baseline W12, W24) | Secondary endpoint: change from baseline VAS W24 |
| [40] https://clinicaltrials.gov/ct2/show/NCT01709578 | Patients also received csDMARDs | ||||||
| Sarilumab monotherapy studies | |||||||
| MONARCH | MTX-IR (n = 369) |
S 200 mg SC A 40 mg SC Placebo SC Q2W 24 weeks |
Secondary endpoint: change from baseline W24 | Secondary endpoints: change from baseline SF-36 physical W24; change from baseline SF-36 mental W24 | Secondary endpoints: change from baseline FACIT-F W24; also measured in RAID domain (change from baseline W24) | Secondary endpoints: change from baseline VAS W24; also measured in RAID domain (change from baseline W24) | Secondary endpoint: change from baseline VAS W24 |
| [41] https://clinicaltrials.gov/ct2/show/NCT02332590 | |||||||
| SC tocilizumab studies | |||||||
| SUMMACTA | DMARDs-IR (n = 1262) |
T 162 mg SC QW T 8 mg/kg IV Q4W 24 weeks |
Secondary endpoint: proportion with ≥ 0.3 change HAQ-DI ≥ 0.3 W24, W97 | Not reported | Not reported | Not reported | Not reported |
| [42] https://clinicaltrials.gov/ct2/show/NCT01194414 | |||||||
| BREVACTA | DMARDs-IR (n = 656) |
T 162 mg SC Placebo SC Q2W 24 weeks |
Secondary endpoint: change from baseline W24; proportion with ≥ 0.3 change W24, W97 | Secondary endpoint: change from baseline SF-36 W24 | Not reported | Secondary endpoint: change from baseline VAS W24 | Not reported |
| [43] https://clinicaltrials.gov/ct2/show/NCT01232569 | |||||||
| IV tocilizumab combination studies | |||||||
| LITHE | MTX-IR (n = 1196) |
T 4 mg/kg IV T 8 mg/kg IV Placebo IV Q4W 52 weeks |
Co-primary endpoint: change from baseline in AUC W52, W104; proportion with ≥ 0.3 change W104 | Secondary endpoint: change from baseline SF-36 W24, W52, W104 | Secondary endpoints: change from baseline FACIT-F W24, W52, W104 | Secondary endpoint: change from baseline VAS W52, W104 | Not reported |
| [44] https://clinicaltrials.gov/ct2/show/NCT00106535 | Patients also receive MTX | ||||||
| OPTION | csDMARD-IR (n = 623) |
T 8 mg/kg IV T 4 mg/kg IV Placebo IV Q4W 24 weeks |
Additional endpoint: change from baseline W24 | Additional endpoint: difference from placebo group SF-36 physical W24; SF-36 mental W24 | Additional endpoint: FACIT-F score, difference from placebo group W24 | Additional endpoint: change from baseline VAS W24 | Not reported |
| [45] https://clinicaltrials.gov/ct2/show/NCT00106548 | Patients also receive MTX | ||||||
| TOWARD | csDMARD-IR (n = 1220) |
T 8 mg/kg IV Placebo IV Q4W 24 weeks |
Secondary endpoint: change from baseline W24 | Secondary endpoint: change from baseline SF-36 W24 | Secondary endpoint: change from baseline FACIT-F W24 | Not reported | Not reported |
| [46] https://clinicaltrials.gov/ct2/show/NCT00106574 | Patients also receive csDMARDs | ||||||
| RADIATE | TNF-IR (n = 499) |
T 8 mg/kg IV T 4 mg/kg IV Placebo IV Q4W 24 weeks |
Additional endpoint: change from baseline W24; proportion with ≥ 0.22 change W24 | Additional endpoint: change from baseline SF-36 physical and mental W24 | Additional endpoint: change from baseline FACIT-F W24 | Additional endpoint: change from baseline; patient’s assessment of pain by VAS W24 | Not reported |
| [47] https://clinicaltrials.gov/ct2/show/NCT00106522 | Patients also receive MTX | ||||||
| IV tocilizumab monotherapy studies | |||||||
| U-ACT-EARLY | Newly diagnosed DMARD-naïve (n = 317) |
T 8 mg/kg IV + MTX T 8 mg/kg IV Placebo + MTX Q4W 104 weeks |
Not reported | Secondary endpoint: change from baseline SF-36 W12, W24, W52, W104 | Secondary endpoint: change from baseline FACIT-F W12, W24, W52, W104 | Secondary endpoint: change from baseline; patient’s assessment of pain by VAS W12, W24, W52, W104 | Not reported |
| [48] https://clinicaltrials.gov/ct2/show/NCT01034137 | |||||||
| FUNCTION | MTX-naïve patients with early progressive RA (n = 1162) |
T 8 mg/kg IV + MTX T 8 mg/kg IV T 8 mg/kg + placebo Placebo + MTX Q4W 104 weeks |
Secondary endpoint: change from baseline W24, W52 | Secondary endpoint: change from baseline SF-36 physical and mental W24, W52 | Not reported | Not reported | Not reported |
| [49] https://clinicaltrials.gov/ct2/show/NCT01007435 | |||||||
| ACT-RAY | MTX-IR (n = 556) |
T 8 mg/kg IV + MTX T 8 mg/kg IV 104 weeks |
Secondary endpoint: change from baseline W24, W52 | Not reported | Not reported | Not reported | Not reported |
| [50] https://clinicaltrials.gov/ct2/show/NCT00810199 | |||||||
| ADACTA | MTX-INT (n = 326) |
T 8 mg/kg IV Q4W A 40 mg SC Q2W 24 weeks |
Not reported | Change from baseline W24 | Change from baseline W24 | Not reported | Not reported |
| [51] https://clinicaltrials.gov/ct2/show/NCT01119859 | |||||||
A adalimumab, AUC area under the curve, csDMARD conventional synthetic disease-modifying antirheumatic drug, DMARD disease-modifying antirheumatic drug, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire Disability Index, INT intolerant, IR inadequate response, IV intravenous, MTX methotrexate, n number of patients, Q2W every 2 weeks, Q4W every 4 weeks, QW weekly, RA rheumatoid arthritis, RAID rheumatoid arthritis impact of disease, S sarilumab, SC subcutaneous, SF-36 Short Form (36 item) Health Survey, T tocilizumab, TNF tumor necrosis factor, VAS visual analog scale, W week