Table 2.
Safety
| Monotherapy (N = 223) |
Combination therapy (N = 372) |
All (N = 595) |
|
|---|---|---|---|
| Patients with any TEAEa, n (%) | 145 (65.0) | 249 (66.9) | 394 (66.2) |
| Patients with any treatment emergent SAE, n (%) | 12 (5.4) | 23 (6.2) | 35 (5.9) |
| Patients with any TEAE leading to deathb,c, n (%) | 1 (0.4) | 1 (0.3) | 2 (0.3) |
| Patients with any TEAE leading to sarilumab discontinuation, n (%) | 34 (15.2) | 59 (15.9) | 93 (15.6) |
| Adverse events of interest | |||
| Neutropenia, n (%) | 24 (10.8) | 60 (16.1) | 84 (14.1) |
| Thrombocytopenia and potential risk of bleeding, n (%) | 12 (5.4) | 27 (7.3) | 39 (6.6) |
| Serious infections, n (%) | 3 (1.3) | 5 (1.3) | 8 (1.3) |
| Herpes zoster, n (%) | 6 (2.7) | 8 (2.2) | 14 (2.4) |
| Tuberculosis, n (%) | 0 (0.0) | 1 (0.3) | 1 (0.2) |
| Hepatic disorders, including LFT elevations, n (%) | 8 (3.6) | 23 (6.2) | 31 (5.2) |
| Confirmed upper/Lower GI perforationsd, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Elevation in lipids, n (%) | 18 (8.1) | 29 (7.8) | 47 (7.9) |
| Cardiovascular adverse eventse, n (%) | 2 (0.9)e | 4 (1.1)f | 6 (1.0) |
| MACE, n (%) | 0 (0.0) | 2 (0.5) | 2 (0.3) |
| Hypersensitivity, n (%) | 19 (8.5) | 24 (6.5) | 43 (7.2) |
| Anaphylaxis, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Injection site reactions, n (%) | 23 (10.3) | 34 (9.1) | 57 (9.6) |
| Malignancyg, n (%) | 0 (0.0) | 2 (0.5) | 2 (0.3) |
| Malignancy excluding NMSC, n (%) | 0 (0.0) | 2 (0.5) | 2 (0.3) |
| DVT/Pulmonary embolismh, n (%) | 1 (0.4) | 1 (0.3) | 2 (0.3) |
| Pregnancyi, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Symptomatic overdosei, n (%) | 0 (0.0) | 1 (0.3) | 1 (0.2) |
| Changes from baseline at week 52 | |||
| ANC (Giga/l), mean (SD) |
N = 46 −2.9 (2.5) |
N = 105 −1.8 (2.2) |
N = 151 −2.2 (2.3) |
| Hemoglobin (g/l), mean (SD) |
N = 77 8.9 (14.0) |
N = 143 5.6 (11.1) |
N = 220 6.8 (12.3) |
| Hba1c (%), mean (SD) |
N = 10 0.02 (0.5) |
N = 26 −0.2 (0.6) |
N = 36 −0.1 (0.6) |
| ANC grade by week 52 | N = 56 | N = 125 | N = 181 |
| Grade 0: ≥ 2.0 Giga/l, n (%) | 36 (64.3) | 90 (72.0) | 126 (69.6) |
| Grade 1: ≥ 1.5 to < 2.0 Giga/l, n (%) | 12 (21.4) | 23 (18.4) | 35 (19.3) |
| Grade 2: ≥ 1.0 to < 1.5 Giga/l, n (%) | 7 (12.5) | 9 (7.2) | 16 (8.8) |
| Grade 3: ≥ 0.5 to < 1.0 Giga/l, n (%) | 1 (1.8) | 3 (2.4) | 4 (2.2) |
| Grade 4: < 0.5 Giga/l, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| ALT grade by week 52 | N = 85 | N = 153 | N = 238 |
| ≤ ULN, n (%) | 71 (83.5) | 124 (81.0) | 195 (81.9) |
| > 1 to 3 × ULN, n (%) | 13 (15.3) | 27 (17.6) | 40 (16.8) |
| > 3 to 5 × ULN, n (%) | 1 (1.2) | 2 (1.3) | 3 (1.3) |
| > 5 × ULN, n (%) | 0 (0.0) | 0 (0.0) | 0 (0) |
ALT alanine transaminase, ANC absolute neutrophil count, bDMARDs biologic disease-modifying antirheumatic drugs, LFT liver function test, MACE major adverse cardiac event, N number of patients, NMSC non-melanoma skin cancer, SAE serious adverse events, SD standard deviation, TEAE treatment-emergent adverse events, TIA transient ischemic attack, tsDMARDs targeted synthetic disease-modifying antirheumatic drugs, ULN upper limit of normal
aAny AE that developed or worsened during the time from the first dose of the study treatment to the end of study or the date of last dose plus 60 days, whichever is earlier
bTEAEs leading to death: renal failure (worsening of renal failure); acute respiratory failure (acute on chronic hypoxemic respiratory failure)
cThere was one additional death due to a post-treatment AE (lung neoplasm malignant [lung cancer])
dPotential upper/lower GI perforations: anal fistula
eDistal left anterior descending artery stenosis and TIA (n = 2)
fAcute myocardial infarction, angina pectoris, myocardial infarction, and stroke (n = 4)
gMalignancy: Lung neoplasm malignant; malignant melanoma/basal cell carcinoma
hDVT/PE: Deep vein thrombosis; thrombophlebitis
iAdverse event of special interest