Efficacy results at weeks 12 and 24 for Parts A* and B
| Part A† | Part B‡ | ||||||
|---|---|---|---|---|---|---|---|
| Placebo→ sirukumab 100 mg every 2 weeks (n=17) | Sirukumab 100 mg every 2 weeks→ placebo (n=14) | Placebo→ sirukumab 100 mg every 2 weeks (n=30) | Sirukumab | ||||
| 100 mg every 2 weeks (n=30) | 100 mg every 4 weeks (n=30) | 50 mg every 4 weeks (n=30) | 25 mg every 4 weeks (n=31) | ||||
| WEEK 12 | |||||||
| ACR20, n (%) | 3 (17.6) | 10 (71.4)¶ | 9 (30.0) | 19 (63.3)§ | 18 (60.0)§ | 17 (56.7) | 19 (61.3%) |
| ACR50, n (%) | 1 (5.9) | 4 (28.6) | 1 (3.3) | 8 (26.7)§ | 7 (23.3) | 8 (26.7) | 6 (19.4%) |
| Per cent improvement of core set variables from baseline, mean (SD) | |||||||
| SJC | 20.1 (34.6) | 54.9 (29.7)¶ | 37.4 (39.7) | 53.5 (46.5) | 49.9 (46.3) | 53.1 (27.9) | 52.4 (29.9) |
| TJC | 14.9 (30.3) | 48.2 (26.3)¶ | 34.4 (39.3) | 51.0 (48.1) | 45.1 (29.8) | 53.5 (30.1) | 47.0 (33.0) |
| Patient's assessment of pain (VAS) | 10.9 (48.0) | 35.2 (45.9) | 16.7 (39.7) | 46.0 (38.8)¶ | 36.7 (41.6)§ | 33.8 (40.9) | 33.1 (39.6) |
| Patient's assessment of disease activity (VAS) | −8.2 (95.2) | 46.9 (40.3)§ | 16.2 (36.3) | 11.6 (142.8) | 36.9 (33.1) | 31.4 (45.1) | 11.4 (111.4) |
| Physician's assessment of disease activity (VAS) | 13.3 (34.8) | 46.9 (28.5)¶ | 26.5 (50.6) | 52.8 (49.7)¶ | 46.5 (26.2) | 51.9 (27.9) | 47.0 (38.1) |
| HAQ-DI | 6.2 (34.1) | 49.4 (29.2)** | 9.0 (40.8) | 18.2 (48.1) | 13.2 (39.7) | 33.4 (29.2) | 30.4 (36.7) |
| CRP | 11.9 (58.3) | 91.2 (4.8)** | −40.4 (182.9) | 82.0 (25.0)** | 35.0 (288.6)** | 88.3 (8.5)** | 80.8 (24.3)** |
| Improvement from baseline in CDAI, mean (SD) | 7.2 (10.5) | 16.7 (8.1)¶ | 13.3 (10.8) | 20.7 (15.2)§ | 18.0 (8.8) | 19.8 (9.8) | 18.2 (10.9) |
| Improvement from baseline in DAS28-CRP, mean (SD) | 0.6 (0.9) | 2.1 (0.8)** | 1.1 (1.0) | 2.2 (1.2)** | 2.0 (0.9)** | 2.2 (0.9)** | 2.0 (1.0)** |
| DAS28-CRP response, n (%) | |||||||
| Good | 1 (5.9) | 5 (35.7)** | 3 (10.0) | 11 (36.7)¶ | 4 (13.3) | 7 (23.3) | 7 (22.6) |
| Moderate | 4 (23.5) | 8 (57.1)** | 15 (50.0) | 17 (56.7)¶ | 22 (73.3) | 20 (66.7) | 19 (61.3) |
| Remission, n (%) | |||||||
| DAS28-CRP <2.6 | 1 (5.9) | 1 (7.1) | 0 | 6 (20.0)§ | 1 (3.3) | 4 (13.3) | 3 (9.7) |
| CDAI ≤2.8 | 1 (5.9) | 1 (7.1) | 0 | 3 (10.0) | 1 (3.3) | 0 | 1 (3.2) |
| Boolean | 0 | 1 (7.1) | 0 | 2 (6.7) | 0 | 0 | 1 (3.2) |
| SDAI ≤3.3 | 0 | 1 (7.1) | 1 (3.3) | 3 (10.0) | 1 (3.3) | 2 (6.7) | 1 (3.2) |
| Change from baseline, mean (SD) | |||||||
| SF-36 PCS score | 2.1 (4.7) | 6.4 (9.7) | 2.6 (8.2) | 6.3 (8.6) | 6.4 (6.4) | 6.4 (5.9) | 5.5 (8.4) |
| SF-36 MCS score | 3.3 (7.9) | 6.4 (11.1) | 5.1 (10.6) | 7.1 (11.6) | 4.0 (10.0) | 7.9 (11.3) | 3.2 (8.5) |
| Improvement from baseline in HAQ-DI, mean (SD) | 0.17 (0.36) | 0.74 (0.45)** | 0.16 (0.56) | 0.40 (0.58) | 0.29 (0.48) | 0.53 (0.55) | 0.47 (0.51) |
| WEEK 24 | |||||||
| ACR20, n (%) | 9 (52.9) | 10 (71.4) | 18 (60.0) | 25 (83.3) | 19 (63.3) | 17 (56.7) | 19 (61.3) |
| ACR50, n (%) | 3 (17.6) | 5 (35.7) | 11 (36.7) | 18 (60.0) | 15 (50.0) | 9 (30.0) | 11 (35.5) |
| Percent improvement of core set variables from baseline, mean (SD) | |||||||
| SJC | 56.3 (34.0) | 60.6 (30.1) | 53.3 (39.9) | 63.6 (55.2) | 60.8 (41.1) | 57.7 (34.2) | 52.6 (42.9) |
| TJC | 44.6 (35.5) | 48.5 (33.3) | 53.3 (46.6) | 69.9 (50.1) | 53.8 (40.0) | 59.3 (33.8) | 53.0 (36.4) |
| Patient's assessment of pain (VAS) | 31.8 (38.1) | 42.8 (46.3) | 37.7 (40.5) | 55.0 (35.7) | 44.9 (46.3) | 35.6 (40.5) | 23.2 (52.7) |
| Patient's assessment of disease activity (VAS) | 11.1 (107.0) | 49.5 (27.8) | 42.1 (40.1) | 37.6 (72.0) | 42.5 (41.0) | 30.6 (46.8) | 4.8 (128.8) |
| Physician's assessment of disease activity | 46.3 (32.5) | 47.6 (39.4) | 50.8 (44.4) | 71.3 (25.9) | 54.4 (26.4) | 55.0 (26.2) | 43.9 (58.4) |
| HAQ-DI | 18.4 (36.3) | 48.0 (32.8) | 28.2 (43.5) | 36.4 (41.0) | 16.1 (38.1) | 35.7 (29.7) | 32.0 (38.0) |
| CRP | 87.1 (31.4) | 84.5 (23.4) | 70.0 (53.2) | 81.7 (24.9) | 73.8 (81.0) | 85.4 (18.2) | 76.0 (36.2) |
| Improvement from baseline in CDAI, mean (SD) | 19.3 (13.5) | 19.4 (9.6) | 21.4 (12.4) | 24.8 (15.2) | 23.6 (14.1) | 22.0 (12.5) | 18.4 (12.3) |
| Improvement from baseline in DAS28-CRP, mean (SD) | 2.2 (1.1) | 2.2 (0.8) | 2.3 (1.2) | 2.8 (1.3) | 2.6 (1.4) | 2.4 (1.1) | 2.0 (1.2) |
| DAS28-CRP response, n (%) | |||||||
| Good | 2 (11.8) | 4 (28.6) | 12 (40.0) | 20 (66.7) | 14 (46.7) | 10 (33.3) | 9 (29.0) |
| Moderate | 13 (76.5) | 10 (71.4) | 13 (43.3) | 8 (26.7) | 11 (36.7) | 18 (60.0) | 19 (61.3) |
| Remission, n (%) | |||||||
| DAS28-CRP <2.6 | 1 (5.9) | 4 (28.6) | 6 (20.0) | 12 (40.0) | 8 (26.7) | 4 (13.3) | 7 (22.6) |
| CDAI ≤2.8 | 0 | 0 | 2 (6.7) | 7 (23.3) | 5 (16.7) | 0 | 2 (6.5) |
| Boolean | 0 | 0 | 1 (3.3) | 4 (13.3) | 2 (6.7) | 0 | 2 (6.5) |
| SDAI ≤3.3 | 0 | 1 (7.1) | 3 (10.0) | 7 (23.3) | 5 (16.7) | 1 (3.3) | 2 (6.5) |
| Change from baseline, mean (SD) | |||||||
| SF-36 PCS score | 5.5 (8.6) | 8.3 (7.5) | 6.6 (8.7) | 7.6 (6.9) | 6.9 (7.4) | 6.8 (7.6) | 5.4 (6.9) |
| SF-36 MCS score | 5.4 (8.9) | 8.0 (12.1) | 8.4 (9.4) | 8.1 (11.1) | 5.8 (9.5) | 7.5 (13.1) | 2.1 (9.8) |
| Improvement from baseline in HAQ-DI, mean (SD) | 0.29 (0.44) | 0.72 (0.48) | 0.41 (0.58) | 0.56 (0.63) | 0.32 (0.61) | 0.56 (0.46) | 0.52 (0.56) |
In Part B, a sequential analysis was performed in which the sirukumab treatment groups were compared with the placebo group in the following order: 100 mg q2w, 100 mg q4w, 50 mg q4w and 25 mg q4w, and if one comparison was not significant, the other remaining comparisons were not performed and were considered to be not significant.
*Five patients (placebo, 2; sirukumab, 3) from 1 site were excluded from efficacy analyses due to concerns about data integrity.
†At week 12 in Part A, patients randomised to placebo crossed over to sirukumab 100 mg every 2 weeks, and patients randomised to sirukumab crossed over to placebo through week 22.
‡At week 12 in Part B, patients randomised to placebo crossed over to sirukumab 100 mg every 2 weeks through week 24.
§p<0.05 versus placebo.
¶p<0.01 versus placebo.
**p<0.001 versus placebo.
ACR20/50, at least 20%/50% improvement in the American College of Rheumatology criteria; CDAI, clinical disease activity indexCRP, C-reactive protein; DAS28-CRP, 28-joint count disease activity score using CRP; HAQ-DI, health assessment questionnaire disability index; SDAI, simplified disease activity index; SF-36 PCS/MCS, 36-item short form health survey physical/mental component summary; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale