Background
Methods
Patients
Study design, randomization and blinding
Safety assessments
Efficacy assessments
Immunogenicity assessment
Statistical analysis
Results
Patient disposition and characteristics
Characteristic | Sirukumab 50 mg q4w (N = 61) | Sirukumab 100 mg q2w (N = 61) | All (N = 122) |
---|---|---|---|
Sex (women), n (%) | 47.0 (77.0) | 43.0 (70.5) | 90 (73.8) |
Age (years), mean (SD) | 55.4 (10.70) | 54.7 (12.16) | 55.1 (11.41) |
Weight (kg), mean (SD) | 55.0 (12.23) | 56.8 (9.71) | 55.9 (11.03) |
Height (cm), mean (SD) | 157.9 (7.90) | 158.4 (7.80) | 158.1 (7.82) |
BMI (kg/m2), mean (SD) | 22.0 (3.98) | 22.6 (3.13) | 22.3 (3.58) |
Disease duration (years), median (range) | 5.0 (0.4–41.0) | 6.3 (0.4–30.0) | 5.8 (0.4–41.0) |
Swollen joints (number 0–66), median (range) | 11.0 (6.0–22.0) | 11.0 (5.0–32.0) | 11.0 (5.0–32.0) |
Tender joints (number 0–68), median (range) | 14.0 (6.0–56.0) | 15.0 (5.0–48.0) | 14.0 (5.0–56.0) |
Patient’s assessment of pain (VAS; 0–10 cm), median (range) | 7.4 (0.7–10.0) | 7.4 (0.5–10.0) | 7.4 (0.5–10.0) |
Patient’s global assessment of disease activity (VAS; 0–10 cm), median (range) | 7.6 (0.6–10.0) | 7.1 (0.6–10.0) | 7.5 (0.6–10.0) |
Physician’s global assessment of disease activity (VAS; 0–10 cm), median (range) | 6.5 (2.6–10.0) | 6.9 (2.0–10.0) | 6.6 (2.0–10.0) |
HAQ-DI score (0–3), median (range) | 1.4 (0.00–2.75) | 1.1 (0.00–2.75) | 1.3 (0.00–2.75) |
CRP (mg/dl), median (range) | 2.7 (0.20– 9.20) | 2.5 (0.31–16.60) | 2.6 (0.20–16.60) |
DAS28-CRP score, median (range) | 5.6 (5.14–6.11) | 5.9 (4.88–6.57) | 5.7 (4.93–6.29) |
SDAI score, median (range) | 33.2 (28.42–40.38) | 38.2 (26.83–52.20) | 34.7 (27.70–42.48) |
CDAI score, median (range) | 30.9 (24.90–37.80) | 33.5 (24.20–47.40) | 31.8 (24.60–38.80) |
Rheumatoid factor-positive, n (%) | 48 (78.7) | 44 (72.1) | 92 (75.4) |
Anti-CCP antibody positive, n (%) | 55 (90.2) | 51 (83.6) | 106 (86.9) |
Safety
Adverse events
Sirukumab 50 mg q4w (N = 61) | Sirukumab 100 mg q2w (N = 61) | All (N = 122) | |
---|---|---|---|
AEs | 56 (91.8) | 58 (95.1) | 114 (93.4) |
Serious AEs | 4 (6.6) | 5 (8.2) | 9 (7.4) |
AEs in ≥ 10% patients | |||
Infections and infestations | 39 (63.9) | 38 (62.3) | 77 (63.1) |
Nasopharyngitis | 27 (44.3) | 27 (44.3) | 54 (44.3) |
Pharyngitis | 6 (9.8) | 7 (11.5) | 13 (10.7) |
General disorders and administration site conditions | 26 (42.6) | 27 (44.3) | 53 (43.4) |
Injection-site erythema | 19 (31.1) | 20 (32.8) | 39 (32.0) |
Injection-site swelling | 10 (16.4) | 12 (19.7) | 22 (18.0) |
Injection-site pruritus | 7 (11.5) | 13 (21.3) | 20 (16.4) |
Investigations | 28 (45.9) | 21 (34.4) | 49 (40.2) |
Alanine aminotransferase increased | 10 (16.4) | 10 (16.4) | 20 (16.4) |
Aspartate aminotransferase increased | 9 (14.8) | 11 (18.0) | 20 (16.4) |
White blood cell count decreased | 7 (11.5) | 7 (11.5) | 14 (11.5) |
Platelet count decreased | 9 (14.8) | 3 (4.9) | 12 (9.8) |
Neutrophil count decreased | 7 (11.5) | 4 (6.6) | 11 (9.0) |
Skin and subcutaneous tissue disorders | 15 (24.6) | 25 (41.0) | 40 (32.8) |
Eczema | 7 (11.5) | 7 (11.5) | 14 (11.5) |
Vascular disorders | 5 (8.2) | 7 (11.5) | 12 (9.8) |
Hypertension | 5 (8.2) | 7 (11.5) | 12 (9.8) |
Serious AEs | |||
Infections and infestations | 1 (1.6) | 2 (3.3) | 3 (2.5) |
Acute sinusitis | 0 | 1 (1.6) | 1 (0.8) |
Hepatitis E | 0 | 1 (1.6) | 1 (0.8) |
Osteomyelitis | 1 (1.6) | 0 | 1 (0.8) |
Gastrointestinal disorders | 1 (1.6) | 1 (1.6) | 2 (1.6) |
Gastroesophageal reflux disease | 0 | 1 (1.6) | 1 (0.8) |
Large intestine polyp | 1 (1.6) | 0 | 1 (0.8) |
Injury, poisoning and procedural complications | |||
Comminuted fracture | 1 (1.6) | 0 | 1 (0.8) |
Musculoskeletal and connective tissue disorders | |||
Intervertebral disc protrusion | 0 | 1 (1.6) | 1 (0.8) |
Neoplasms benign, malignant and unspecified | |||
Borderline serous tumor of ovary | 0 | 1 (1.6) | 1 (0.8) |
Psychiatric disorders | |||
Schizophrenia | 1 (1.6) | 0 | 1 (0.8) |
Reproductive system and breast disorders | |||
Endometriosis | 0 | 1 (1.6) | 1 (0.8) |
Serious adverse events
Hematology and clinical laboratory values
Parameter | Total (N) | Grade 0 at baseline | Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
---|---|---|---|---|---|---|---|
Neutrophils decreased | |||||||
Sirukumab 50 mg q4w | 61 | 61 (100.0) | 33 (54.1) | 17 (27.9) | 8 (13.1) | 3 (4.9) | 0 |
Sirukumab 100 mg q2w | 61 | 61 (100.0) | 34 (55.7) | 14 (23.0) | 11 (18.0) | 2 (3.3) | 0 |
Platelets decreased | |||||||
Sirukumab 50 mg q4w | 61 | 61 (100.0) | 44 (72.1) | 17 (27.9) | 0 | 0 | 0 |
Sirukumab 100 mg q2w | 61 | 61 (100.0) | 54 (88.5) | 6 (9.8) | 0 | 0 | 1 (1.6)a |
Leukocytes decreased | |||||||
Sirukumab 50 mg q4w | 61 | 61 (100.0) | 34 (55.7) | 21 (34.4) | 6 (9.8) | 0 | 0 |
Sirukumab 100 mg q2w | 61 | 61 (100.0) | 42 (68.9) | 11 (18.0) | 6 (9.8) | 2 (3.3) | 0 |
Lymphocytes decreased | |||||||
Sirukumab 50 mg q4w | 61 | 58 (95.1) | 51 (83.6) | 3 (4.9) | 4 (6.6) | 0 | 0 |
Sirukumab 100 mg q2w | 61 | 58 (95.1) | 50 (82.0) | 1 (1.6) | 7 (11.5) | 0 | 0 |
Alanine aminotransferase increased | |||||||
Sirukumab 50 mg q4w | 61 | 58 (95.1) | 30 (49.2) | 26 (42.6) | 2(3.3) | 0 | 0 |
Sirukumab 100 mg q2w | 61 | 56 (91.8) | 31 (50.8) | 24 (39.3) | 1 (1.6) | 0 | 0 |
Aspartate aminotransferase increased | |||||||
Sirukumab 50 mg q4w | 61 | 59 (96.7) | 33 (54.1) | 25 (41.0) | 1 (1.6) | 0 | 0 |
Sirukumab 100 mg q2w | 61 | 55 (90.2) | 32 (52.5) | 23 (37.7) | 0 | 0 | 0 |
Bilirubin increased | |||||||
Sirukumab 50 mg q4w | 61 | 61 (100.0) | 48 (78.7) | 10 (16.4) | 3 (4.9) | 0 | 0 |
Sirukumab 100 mg q2w | 61 | 61 (100.0) | 47 (77.0) | 10 (16.4) | 4 (6.6) | 0 | 0 |
Cholesterol increased | |||||||
Sirukumab 50 mg q4w | 59 | 59 (100.0) | 51 (83.6) | 5 (8.2) | 3 (4.9) | 0 | 0 |
Sirukumab 100 mg q2w | 60 | 60 (100.0) | 54 (88.5) | 5 (8.2) | 1 (1.6) | 0 | 0 |
Triglycerides increased | |||||||
Sirukumab 50 mg q4w | 59 | 55 (93.2) | 34 (55.7) | 20 (32.8) | 0 | 1 (1.6) | 0 |
Sirukumab 100 mg q2w | 60 | 54 (90.0) | 33 (54.1) | 20 (32.8) | 0 | 1 (1.6) | 0 |
Efficacy
Efficacy parameter | Sirukumab 50 mg q4w (N = 61) | Sirukumab 100 mg q2w (N = 61) |
---|---|---|
ACR20 response, n (%) | ||
Week 16 | 47 (77.0) | 44 (72.1) |
Week 24 | 45 (73.8) | 50 (82.0) |
Week 52 | 39 (63.9) | 46 (75.4) |
ACR50 response, n (%) | ||
Week 16 | 29 (47.5) | 35 (57.4) |
Week 24 | 30 (49.2) | 39 (63.9) |
Week 52 | 29 (47.5) | 35 (57.4) |
ACR70 response, n (%) | ||
Week 16 | 16 (26.2) | 20 (32.8) |
Week 24 | 15 (24.6) | 22 (36.1) |
Week 52 | 20 (32.8) | 24 (39.3) |
HAQ-DI | ||
Week 16 median decrease from baseline, % | 41.2 | 51.5 |
Week 52 median decrease from baseline, % | 44.5 | 70.0 |
CRP levels (mg/dl), mean (SD) | ||
Week 16 | 0.02 (0.05) | 0.02 (0.02) |
Week 52 | 0.02 (0.06) | 0.02 (0.02) |
DAS28-CRP response | ||
Week 16 responders, n (%) | 55 (90.2) | 59 (96.7) |
Week 52 responders, n (%) | 45 (73.8) | 50 (82.0) |
DAS28-CRP remission | ||
Week 16 remitters, n (%) | 28 (45.9) | 30 (49.2) |
Week 52 remitters, n (%) | 29 (47.5) | 32 (52.5) |
SDAI | ||
Week 16 change from baseline, mean (SD) | −22.4 (12.44) | −25.9 (13.99) |
Week 52 change from baseline, mean (SD) | −23.3 (14.02) | −28.5 (15.94) |
CDAI | ||
Week 16 change from baseline, mean (SD) | −19.4 (12.14) | −22.7 (13.23) |
Week 52 change from baseline, mean (SD) | −20.4 (13.83) | −25.3 (15.26) |
HAQ-DI response | ||
Week 16 responders, n (%) | 46 (75.4) | 41 (67.2) |
Week 52 responders, n (%) | 44 (72.1) | 41 (67.2) |
Efficacy assessments post sirukumab administration
Efficacy parameter | Sirukumab 50 mg q4w | Sirukumab 100 mg q2w |
---|---|---|
ACR20 response | ||
Methotrexate | ||
Week 52a | 29/44 (65.9) | 34/42 (81.0) |
Week 52b | 29/36 (80.6) | 34/38 (89.5) |
Week 16, posttreatment phaseb | 32/36 (88.9) | 32/38 (84.2) |
DMARDs (including methotrexate) | ||
Week 52a | 31/49 (63.3) | 34/44 (77.3) |
Week 52b | 31/38 (81.6) | 34/38 (89.5) |
Week 16, posttreatment phaseb | 33/38 (86.8) | 32/38 (84.2) |
Corticosteroid (oral) | ||
Week 52a | 2/7 (28.6) | 8/11 (72.7) |
Week 52b | 2/3 (66.7) | 8/9 (88.9) |
Week 16, posttreatment phaseb | 3/3 (100.0) | 9/9 (100.0) |
Corticosteroid (oral, intramuscular) | ||
Week 52a | 4/11 (36.4) | 11/15 (73.3) |
Week 52b | 4/6 (66.7) | 11/12 (91.7) |
Week 16, posttreatment phaseb | 5/6 (83.3) | 12/12 (100.0) |
No DMARD and corticosteroid | ||
Week 52a | 7/11 (63.6) | 8/12 (66.7) |
Week 52b | 8/8 (100.0) | 8/10 (80.0) |
Week 16, posttreatment phaseb | 8/8 (100.0) | 8/10 (80.0) |
ACR50 response | ||
Methotrexate | ||
Week 52a | 21/44 (47.7) | 24/42 (57.1) |
Week 52b | 21/36 (58.3) | 24/38 (63.2) |
Week 16, posttreatment phaseb | 23/36 (63.9) | 27/38 (71.1) |
DMARDs (including methotrexate) | ||
Week 52a | 22/49 (44.9) | 24/44 (54.5) |
Week 52b | 22/38 (57.9) | 24/38 (63.2) |
Week 16, posttreatment phaseb | 23/38 (60.5) | 27/38 (71.1) |
Corticosteroid (oral) | ||
Week 52a | 0/7 (0) | 6/11 (54.5) |
Week 52b | 0/3 (0) | 6/9 (66.7) |
Week 16, posttreatment phaseb | 1/3 (33.3) | 8/9 (88.9) |
Corticosteroid (oral, intramuscular) | ||
Week 52a | 1/11 (9.1) | 9/15 (60.0) |
Week 52b | 1/6 (16.7) | 9/12 (75.0) |
Week 16, posttreatment phaseb | 2/6 (33.3) | 11/12 (91.7) |
No DMARD and corticosteroid | ||
Week 52a | 7/11 (63.6) | 8/12 (66.7) |
Week 52b | 7/8 (87.5) | 8/10 (80.0) |
Week 16, posttreatment phaseb | 7/8 (87.5) | 8/10 (80.0) |
DAS28-CRP score | ||
All, n | 61 | 61 |
Week 52,b n | 47 | 52 |
Mean (SD) | 2.4 (1.07) | 2.3 (1.03) |
Week 16, posttreatment phase, nb | 61 | 60 |
Mean (SD) | 2.5 (1.17) | 2.4 (1.19) |
Methotrexate, n | 44 | 42 |
Week 52, nb | 36 | 38 |
Mean (SD) | 2.5 (1.09) | 2.5 (0.94) |
Week 16, posttreatment phase, nb | 44 | 41 |
Mean (SD) | 2.5 (1.10) | 2.6 (1.18) |
Corticosteroid (oral, intramuscular), n | 11 | 15 |
Week 52, nb | 6 | 12 |
Mean (SD) | 3.0 (1.69) | 1.9 (0.97) |
Week 16, posttreatment phase, nb | 11 | 15 |
Mean (SD) | 3.0 (1.59) | 2.1 (0.89) |