Bullet points
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As compared to a comparator cohort treated with ETA a significantly higher number of patients with systemic JIA responded to treatment with TOC or the IL-1 inhibitors anakinra and canakinumab
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Improvement was observed in systemic symptoms as well as arthritis
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A significantly larger proportion of patients reached JADAS-remission upon treatment with TOC or upon IL-1is than with etanercept but only a minority of patients reached ACR preliminary criteria for inactive disease
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Serious adverse events including infections were more frequent upon treatment with TOC
Background
Methods
Effectiveness assessment
Safety assessment
Statistics
Results
Etanercept | Tocilizumab 1. Biologic | Tocilizumab switcher | IL-1 inhibitors (anakinra or Canakinumab) 1. Biologic | IL-1 inhibitors (anakinra or canakinumab) switcher | |
---|---|---|---|---|---|
Patient numbers | 143 | 37 | 34 | 17 | 43 (30 + 13) |
Gender (female) | 72 (50.3%) | 20 (54%) | 17 (50%) | 6 (35%) | 22 (52%) |
Age at onset (years) | |||||
mean +/-SD | 5.0 +/- 3.8 | 5.8 +/- 4.3 | 3.7 +/- 3.4 | 6.8 +/- 4.7 | 4.5 +/- 3.2 |
median (IQR) | 4.1 (2.3; 6.4) | 4.9 (2.2; 8.1) | 2.6 (1.4; 4.4) | 5.2 (3.5; 11.2) | 3.7 (247; 5.3) |
Age at bDMARD start (years) | |||||
mean +/- SD | 9.4 +/- 5.0 | 7.8 +/- 4.9 | 10.7 +/- 4.4 | 9.2 +/- 4.8 | 9.6 +/- 4.6 |
median (IQR) | 8.2 (5.3; 13.0) | 7.2 (3.2; 12.0) | 10.6 (8.3; 13.7) | 8.1 (5.1; 13.3) | 8.4 (5.7; 13.2) |
Disease duration (years) | |||||
mean +/- SD | 4.5 +/- 4.1 | 2.0 +/- 2.6 | 7.0 +/- 4.3 | 4.1 +/- 4.0 | 5.1 +/- 3.9 |
median (IQR) | 3.3 (1.1; 6.6)) | 0.8 (0.3; 2.5) | 7.4 (3.6; 9.8) | 2.8 (0.6; 7.0) | 5.2 (1.5; 8.7) |
Pretreatment oral | |||||
steroids | 143 (100%) | 37 (100%) | 34 (100%) | 11 (65%) | 41 (95%) |
steroid pulse therapy | 24 (16.8%) | 10 (27%) | 6 (18%) | 5 (29%) | 12 (28%) |
i.a. steroids | 42 (29.4%) | 4 (11%) | 7 (21%) | 0 | 10 (23%) |
MTX | 126 (88.1%) | 29 (78%) | 31 (91%) | 8 (47%) | 36 (83%) |
other DMARDs | 136 (95.1%) | 6 (16%) | 12 (35%) | 3 (18%) | 20 (47%) |
biologics | 2 (1.4%) | 0 | 34 (100%) | 0 | 39 (65.0%) |
abatacept | 0 | 0 | 1 (3%) | 0 | 0 |
adalimumab | 0 | 0 | 3 (9%) | 0 | 3 (5.0%) |
anakinra | 2 (1.4%) | 0 | 18 (53%) | 0 | n.a |
canakinumab | 0 | 0 | 2 (6%) | 0 | n.a. |
etanercept | 0 | 0 | 27 (79%) | 0 | 32 (74.0%) |
infliximab | 0 | 0 | 1 (3%) | 0 | 0 |
tocilizimab | 0 | 0 | 0 | 0 | 9 (21%) |
Concomitant treatment at enrolment | |||||
steroids | 118 (82.5%) | 19 (51%) | 12 (34%) | 8 (47%) | 19 (44%) |
MTX | 116 (81.1%) | 25 (68%) | 21 (62%) | 5 (29%) | 18 (42%) |
other DMARDs | 34 (23.8%) | 3 (8%) | 3 (9%) | 2 (12%) | 4 (10%) |
Systemic manifestations at enrolment | |||||
fever | 1/13 (7.7%) | 16/30 (53%) | 7/32 (22%) | 7/14 (50%) | 5/16 (31%) |
exanthema | 2/13 (15.4%) | 11/30 (37%) | 7/32 (22%) | 8/15 (53%) | 2/16 (13%) |
hepatomegaly | 0/2 (0%) | 9/20 (45%) | 2/14 (14%) | 1/9 (11%) | 1/7 (14%) |
splenomegaly | 0/13 (0%) | 7/30 (23%) | 3/32 (9%) | 2/15 (13%) | 2/16 (13%) |
serositis | 0/13 (0%) | 5/29 (17%) | 1/31 (3%) | 1/15 (7%) | 1/16 (6%) |
any systemic manifestation | 2 (1.4%) | 21/31 (68%) | 9/34 (27%) | 9/15 (60%) | 7/16 (44%) |
Disease activity joints | |||||
swollen | 114 (79.7%) | 21 (57%) | 21 (62%) | 9 (56%) | 19 (51%) |
tender | 116 (81.1%) | 25 (68%) | 21 (62%) | 9 (56%) | 21 (57%) |
LOM | 121 (84.6%) | 25 (68%) | 27 (79%) | 8 (50%) | 23 (62%) |
active | 120 (83.9%) | 24 (65%) | 25 (74%) | 9 (56%) | 22 (59%) |
number of active joints mean +/-SD | 9.0 +/- 11.2 | 5.1 +/- 8.5 | 5.6 +/- 8.4 | 2.3 +/- 2.3 | 3.2 +/- 4.8 |
median (IQR) | 4.0 (2.0; 11.0) | 3.0 (0.0; 6.0) | 3.0 (0.3; 7.5) | 2.5 (0.0; 4.3) | 1.0 (0.0; 4.0) |
ESR >20 mm/1 h | 107/135 (79.3%) | 21 (66%) | 12 (55%) | 4/8 (50%) | 16/31 (52%) |
CRP >6 mg/l | 113/137 (82.5%) | 26 (79%) | 18 (64%) | 11/15 (73%) | 20/34 (59%) |
JADAS-10 mean +/- SD (0–14)] | 20.7 +/- 9.1 | 18.8 +/- 10.4 | 14.2 +/- 10.5 | 14.2 +/- 9.7 | 13.0 +/- 9.8 |
JADAS-10 CRP mean +/- (0–40) | 22.2 +/- 9.8 | 22.3 +/- 11.2 | 15.3 +/- 9.9 | 4.3 +/- 10.2 | 13.4 +/- 10.6 |
Effectiveness
JADAS-10; median (IQR)a
| Month 0 | Month 3 | Month 6 | Month 12 | Month 18 | Month 24 | Last observation |
ETA | 20.8 (14; 28.4) | 6.9 (2.5; 14.3) | 6.2 (1.1; 14.7) | 3.8 (0.7; 15.7) | 4.1 (1.5; 15.2) | 3.3 (0.7; 9.4) | 9.1 (2.1; 19.1) |
TOC | 16.9 (8.1; 24.8) | 3.6 (0.8; 10.7) | 1.5 (0.2; 3.8) | 1.6 (0.4; 6.7) | 0.9 (0.2; 2.0) | 0.9 (0.1; 7.5) | 0.9 (0.1; 4) |
IL-1i | 13 (6.7; 20.6) | 0.8 (0.2; 1.6) | 0.6 (0.2; 2.1) | 0.8(0.2; 2.6) | 0.2 (0; 1.9) | 0.2 (0.1; 0.8) | 0.8 (0.1; 5.1) |
Patients with active systemic signs; n (%)b
| |||||||
ETA | 2 (1%) | 0 | 0 | 2 (2.5%) | 0 | 0 | 1 (1%) |
TOC | 30 (42%) | 5 (14%) | 3 (6%) | 3 (7%) | 2 (5%) | 1 (4%) | 4 (7%) |
IL-1i | 40 (63%) | 9 (32%) | 8 (22%) | 8 (21%) | 8 (26%) | 4 (17%) | 6 (11%) |
Active joints; median (IQR)a
| |||||||
ETA | 4 (2; 11) | 1 (0; 3) | 1 (0; 5) | 0 (0; 4) | 0.5 (0; 4) | 0.5 (0; 4) | 1 (0; 6) |
TOC | 3.0 (0; 6) | 0 (0; 0.5) | 0 (0; 0.3) | 0 (0; 1.0) | 0 (0; 0) | 0 (0; 1.0) | 0 (0; 0) |
IL-1i | 2 (0; 5) | 0 (0; 0.3) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) |
Patients with active joints; n (%)b
| |||||||
ETA | 121 (85%) | 48 (53%) | 49 (52%) | 39 (48%) | 36 (50%) | 36 (50%) | 67 (53%) |
TOC | 49 (69%) | 9 (26%) | 12 (25%) | 13 (29%) | 7 (19%) | 8 (29%) | 15 (21%) |
IL-1i | 34 (60%) | 7 (25%) | 6 (17%) | 8 (21%) | 7 (23%) | 2 (9%) | 12 (21%) |
Patients on steroid use; n (%)b
| |||||||
ETA | 119 (83%) | 66 (72%) | 73 (76%) | 48 (59%) | 36 (49%) | 35 (56%) | 65 (49%) |
TOC | 32 (44%) | 13 (35%) | 16 (31%) | 7 (14%) | 6 (15%) | 8 (27%) | 7 (11%) |
IL-1i | 27 (45%) | 12 (48%) | 15 (45%) | 10 (29%) | 7 (25%) | 6 (27%) | 12 (24%) |
Etanercept | Tocilizumab | Interleukin-1 inhibitor | |
---|---|---|---|
Discontinuations | 77 (53.8%) | 28 (39.4%) | 28 (46.7%) |
Inefficacy | 62 (43.4%) | 6 (8.5%) | 13 (21.7%) |
Intolerance | 5 (3.5%) | 14 (19.7%) | 1 (1.7) |
Remission | 0 | 18 (25.4%) | 11 (18.3) |
Othersa
| 15 (10.5%) | 3 (4.2%) | 3 (5.0%) |
Early effectiveness
Effectiveness in early disease
Effectiveness in biologic-naïve patients compared to those pre-treated
Safety
Etanercept | Tocilizumab | IL-1 inhibitors | ||||||
---|---|---|---|---|---|---|---|---|
n = 143; 355.8PY | Rate per patient year (95&CI) |
n = 72; 111.6PY | Rate per patient year (95&CI) | Rate per patient year (95&CI)a
|
n = 60; 116.8PY | Rate per patient year (95&CI) | Rate per patient year (95&CI)a
| |
AE | 71 | 0.20 (0.16–0.25) | 118 | 1.06 (0.88–1.27) | 5.3 (3.9–7.1)
p < 0.0001 | 81 | 0.69 (0.56–0.86) | 3.5 (2.5–4.7)
p > 0.05 |
SAE | 18 | 0.05 (0.03–0.08) | 14 | 0.13 (0.07–0.21) | 2.5 (1.2–5.0)
p = 0.01 | 17 | 0.15 (0.07–0.21) | 2.9 (1.5–5.6)
P = 0.002 |
JIA-Reactivation | 4 | 0.01 (0.00–0.03) | 7 | 0.06 (0.03–1.31) | 5.6 (1.6–19.1)
p = 0.006 | 10 | 0.86 (0.05–0.16) | 7.6 (2.4–24.3)
p = 0.0006 |
MAS | 3 | 0.01 (0.00–0.03) | 5 | 0.05/0.02–0.11) | 5.3 (1.2–22.2)
p = 0.02 | 3 | 0.03 (0.01–0.08) | 3.0 (0.6–15.1)
p > 0.05 |
hypersensitivity | 5 | 0.01 (0.01–0.03) | 4 | 0.04 (0.01–0.10) | 2.6 (0.7–9.5)
p > 0.05 | 2 | 0.02 (0.00–0.07) | 1.2 (0.2–6.3)
p > 0.05 |
infections | 16 | 0.05 (0.03–0.08) | 55 | 0.49 (0.38–0.64) | 11.0 (6.3–19.1)
p < 0.0001 | 39 | 0.33 (0.24–0.46) | 7.4 (4.1–13.3)
p < 0.0001 |
neutropenia | 1 | 0.00 (0.00–0.02) | 6 | 0.05 (0.02–0.12) | 19.1 (2.3–158)
p = 0.006 | 1 | 0.01 (0.00–0.06) | 3.0 (0.2–48.7)
p > 0.05 |
thrombocytopenia | 1 | 0.00 (0.00–0.02) | 1 | 0.01 (0.00–0.06) | 3.2 (0.2–51)
p > 0.05 | 1 | 0.01 (0.00–0.06) | 3.0 (0.2–48.7)
p > 0.05 |
elevated Transaminases | 8 | 0.02 (0.01–0.45) | 4 | 0.04 (0.01–0.10) | 1.6 (0.5–5.3)
p > 0.05 | 1 | 0.01 (0.00–0.06) | 0.4 (0.05–3.0)
p > 0.05 |
hair loss | 4 | 0.01 (0.00–0.03) | 2 | 0.02 (0.00–0.07) | 1.6 (0.3–8.7)
p > 0.05 | 0 | ||
skin signs and symptoms | 6 | 0.02 (0.01–0.03) | 3 | 0.03 (0.01–0.08) | 1.6 (0.4–6.4)
p > 0.05 | 0 | ||
neurol. signs and symptoms | 3 | 0.01 (0.00–0.03) | 11 | 0.10 (0.05–1.78) | 11.7(3.3–42.0)
p = 0.0001 | 0 |