Study author/ sponsor | Target | Level of evidence | Targeted immunosuppressive agent | GC start dosage /taper | Classification criteria | Disease stage (total N) | Primary end point | Primary end point met (YES/NO) | Duration of follow-up |
Villiger et al22 | IL-6 | RCT | Tocilizumab i.v. 8 mg/kg or placebo 1 x/4 wk until 52 wk | 1 mg/kg/day+taper to 0.1 mg/kg/day by wk 12+taper to 0 | ACR1990 and TAB + or MRA+ | New-onset Relapsing (30) | Complete remission rate at a GC dose of 0.1 mg/kg/day at 12 wk | YES 85% vs 40% p=0.03 GC sparing | 52 wk |
Stone et al23 | IL-6 | RCT | Tocilizumab s.c. 162 mg four arms: 1 x/wk +26 wk GC 1 x/2wk +26 wk GC placebo +26 wk GC placebo +52 wk GC | 20–60 mg/day + 26-or 52 wk taper | ACR1990, PMR and TAB + or PET+ | New-onset Relapsing (251) | GC-free remission rate at 52 wk in each TCZ group vs placebo 26 wk GC | YES 56% and 53% vs 14% p<0.001 GC sparing | 52 wk |
Christ et al26 | IL-6 | Open-label | Tocilizumab i.v. 1×8 mg/kg followed by s.c. 162 mg 1 x/wk | 500 mg methyl-prednisolone i.v. during 3 days | ACR1990, PMR and TAB + or PET+ | New-onset (18) | Remission within 31 days | NO mean time to first remission: 11.1 wk | 52 wk |
Schmidt et al30 | IL-6 | RCT | Sirukumab three arms | 20–60 mg/day+standard taper | High ESR/CRP and cranial or PMR clinic and TAB/imaging+ | New-onset Relapsing (161) | Sustained remission rate at 52 wk | Unclear Only 17.4% reached 52 wk | 52 wk early terminated |
Conway et al38 | IL-12/ IL-23 | Open-label | Ustekinumab s.c. 90 mg at wk 0, 4, then 1 x/12 wk | Median 20 mg/day+standard taper | ACR1990 or imaging+ | Relapsing (25) | GC dose prior to ustekinumab vs GC dose at 52 wk | YES 20 vs 5 mg/day p<0.001 | 52 wk |
Matza et al39 | IL-12/ IL-23 | Open-label | Ustekinumab s.c. 90 mg at wk 0, 4, 12, 20, 28, 36, 44 | 20–60 mg/day + 24 wk taper | GCA or PMR-symptoms and TAB/imaging+ | New-onset Relapsing (13) | GC-free remission rate at 52 wk | NO 23% | 52 wk early terminated |
Venhoff et al36 | IL17(A) | RCT | Secukinumab s.c. 300 mg or placebo at wk 0, 1, 2, 3, 4, then1x/4 wk | 26 wk taper | ACR1990 or imaging+ | New-onset Relapsing (50) | Sustained remission rate at 28 wk | YES 70% vs 20% | 52 wk |
Langford et al42 | T cell | RCT | Abatacept i.v. 10 mg/kg open-label, then at 12 wk randomised | 28 wk taper | ACR1990 | New-onset Relapsing (49) | Relapse-free survival rate at 12 mo | YES 48% vs 31% p=0.049 | 12 mo |
Koster et al41 | JAK 1/2 | Open-label | Baricitinib 4 mg/day | 10–30 mg/day+standard taper | TAB + or imaging+ | Relapsing (15) | Safety (frequency of AE and SAE) | YES | 52 wk |
Cid et al40 | GM-CSF | RCT | Mavrilimumab s.c. 150 mg 1 x/2 wk or placebo | 20–60 mg/day+26 wk taper | TAB + or imaging+ | New-onset Relapsing (70) | The time to first adjudicated flare by week 26 | YES NE vs 25.1 wk p=0.0263 | 26 wk |
Hoffman et al19 | TNF-α | RCT | Infliximab i.v. 5 mg/kg or placebo at week 0, 2, 6 then 1 x/8 wk | 40–60 mg/day+22 wk taper | ACR1990 | New onset (44) | Relapse-free rate through 22 wk | NO 43% vs 50% p=0.65 No GC-sparing | 22 wk early terminated |
Seror et al20 | TNF-α | RCT | Adalimumab s.c. 40 mg 1 x/2 wk or placebo during 10 wk | 0.7 mg/kg/day+standard taper | ACR1990 partly TAB+ | New onset (70) | Remission rate on less than 0.1 mg/kg GC at 26 wk | NO 59% vs 50% p=0.46 No GC-sparing | 26 wk |
Martinez et al21 | TNF-α | RCT | Etanercept s.c. 25 mg 2 x/wk or placebo | Median 15 mg/day+standard taper | TAB+ | New onset Relapsing (17) | GC-free remission rate at 12 months | NO 50% vs 22% GC-sparing | 12 mo |
AE, adverse events; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; GC, glucocorticoids; i.v., intravenously; mo, month; MRA, MR angiography; NE, not estimable; PET, positron emission tomography; PMR, polymyalgia rheumatica; RCT, randomised controlled trial; SAE, serious AEs; s.c., subcutaneous; TAB, temporal artery biopsy; TCZ, tocilizumab; TNF, tumour necrosis factor; wk, week.