Table 1.
Adverse event incidence rates per 100 patient years and incidence of most common adverse events per study period
| Primary treatment period (96 weeks) | Assessed treatment-free period | OLE | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Ocrelizumab 2000 mg n = 55 |
Ocrelizumab 600 mg n = 55 |
Placebo n = 54 |
Interferon β-1a n = 54 |
Ocrelizumab 2000 mg n = 50 |
Ocrelizumab 600 mg n = 48 |
Placebo n = 49 |
Interferon β-1a n = 49 |
Ocrelizumab 600 mg n = 103 |
|
| AE incidence rates per 100 patient years + 95% CI | |||||||||
| Any AE | 370.1 (331.9, 412.6) | 337.0 (301.4, 376.7) | 343.4 (308.3, 382.5) | 281.4 (249.1, 317.9) | 186.4 (157.3, 220.7) | 75.6 (58.0, 98.5) | 90.8 (70.3, 117.1) | 69.9 (52.3, 93.3) | 112.2 (104.1, 120.8) |
| SAE | 8.0 (3.8, 16.8) | 7.6 (3.6, 16.0) | 6.2 (2.8, 13.9) | 13.1 (7.4, 23.1) | 7.0 (2.9, 16.7) | 5.5 (2.1, 14.7) | 1.5 (0.2, 10.9) | 3.0 (0.8, 12.1) | 5.3 (3.8, 7.4) |
| Infections | 81.1 (64.3, 102.3) | 87.2 (70.1, 108.6) | 87.1 (70.4, 107.9) | 58.9 (45.1, 76.9) | 34.8 (23.5, 51.5) | 23.4 (14.5, 37.6) | 33.8 (22.3, 51.4) | 21.3 (12.6, 35.9) | 42.6 (37.8, 48.1) |
| Serious infections | 2.3 (0.6, 9.1) | 3.3 (1.1, 10.1) | 5.2 (2.2, 12.5) | 3.3 (1.1, 10.2) | 0 | 0 | 0 | 1.5 (0.2, 10.8) | 2.9 (1.8, 4.6) |
| AEs occurring in > 10% of patients in any group in any period, n (%)a | |||||||||
| Infusion-related reaction | 27 (49.1) | 22 (40.0) | 26 (48.1) | 16 (29.6) | NA | NA | NA | NA | 23 (22.3) |
| MS relapse | 11 (20.0) | 15 (27.3) | 22 (40.7) | 25 (46.3) | 16 (32.0) | 9 (18.8) | 6 (12.2) | 6 (12.2) | 26 (25.2) |
| Nasopharyngitis | 9 (16.4) | 8 (14.5) | 6 (11.1) | 6 (11.1) | 6 (12.0) | 2 (4.2) | 3 (6.1) | 4 (8.2) | 18 (17.5) |
| Urinary tract infection | 7 (12.7) | 5 (9.1) | 9 (16.7) | 7 (13.0) | 3 (6.0) | 0 | 2 (4.1) | 0 | 21 (20.4) |
| Upper respiratory tract infection | 8 (14.5) | 9 (16.4) | 6 (11.1) | 4 (7.4) | 1 (2.0) | 2 (4.2) | 3 (6.1) | 1 (2.0) | 14 (13.6) |
| Respiratory tract infection | 2 (3.6) | 4 (7.3) | 6 (11.1) | 1 (1.9) | 0 | 0 | 1 (2.0) | 0 | 6 (5.8) |
| Headache | 9 (16.4) | 7 (12.7) | 10 (18.5) | 9 (16.7) | 3 (6.0) | 0 | 1 (2.0) | 1 (2.0) | 7 (6.8) |
| Back pain | 4 (7.3) | 4 (7.3) | 4 (7.4) | 6 (11.1) | 0 | 1 (2.1) | 4 (8.2) | 1 (2.0) | 6 (5.8) |
| Fatigue | 8 (14.5) | 3 (5.5) | 2 (3.7) | 4 (7.4) | 1 (2.0) | 1 (2.1) | 1 (2.0) | 0 | 8 (7.8) |
| Insomnia | 8 (14.5) | 2 (3.6) | 1 (1.9) | 1 (1.9) | 2 (4.0) | 0 | 0 | 0 | 4 (3.9) |
| SAEs occurring in patients in any group in any period, n (%)a | |||||||||
| Total number of patients with at least one serious adverse event | 6 (10.9) | 4 (7.3) | 3 (5.6) | 10 (18.5) | 5 (10.0) | 4 (8.3) | 1 (2.0) | 2 (4.1) | 14 (13.6) |
| Overall total number of events | 7 | 5 | 3 | 11 | 5 | 4 | 1 | 2 | 27 |
| Anal abscess | 0 | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cystitis | 0 | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Diverticulitis | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Encephalitis | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Gastroenteritis | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 | 0 |
| Gingivitis | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Influenza | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Oral herpes | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 | 0 |
| Pyelonephritis | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Bronchitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (2.0) | 1 (1.0) |
| Pneumonia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (1.9) |
| Urinary tract infection | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (1.9) |
| Cellulitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Hepatitis A | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Infection | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Infective exacerbation of chronic obstructive airways disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Sepsis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Tracheobronchitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| MS relapse | 0 | 0 | 0 | 2 (3.7) | 0 | 0 | 0 | 0 | 0 |
| Epilepsy | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Muscle spasticity | 0 | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Seizure | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Uhthoff’s phenomenon | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Upper abdominal pain | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 | 0 |
| Colitis | 0 | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Strangulated inguinal hernia | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Large intestine polyp | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Salivary duct inflammation | 0 | 0 | 0 | 0 | 0 | 1 (2.1) | 0 | 0 | 0 |
| Subileus | 0 | 0 | 0 | 0 | 0 | 1 (2.1) | 0 | 0 | 0 |
| Anxiety | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Suspected suicide attempt | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Acute psychosis | 0 | 0 | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 0 |
| Suicidal ideation | 0 | 0 | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 0 |
| Retinal artery occlusion | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Systemic inflammatory response syndrome | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Death | 0 | 0 | 0 | 0 | 0 | 1 (2.1) | 0 | 0 | 0 |
| Drug withdrawal syndrome | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (2.0) | 0 |
| Pyrexia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Hypersensitivity | 0 | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Infusion-related reaction | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Fall | 0 | 0 | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 0 |
| Injury | 0 | 0 | 0 | 0 | 0 | 0 | 1 (2.0) | 0 | 0 |
| Subdural hematoma | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Ureterolithiasis | 1 (1.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Ovarian mass | 0 | 0 | 0 | 1 (1.9) | 0 | 0 | 0 | 0 | 0 |
| Uterine prolapse | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Immune thrombocytopenic purpura | 0 | 0 | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 0 |
| Breast cancer | 0 | 0 | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 0 |
| Pregnancy | 0 | 0 | 0 | 0 | 0 | 1 (2.1) | 0 | 0 | 0 |
| Back pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Rotator cuff syndrome | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Anemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Amylase increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Blood potassium increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Erythema nodosum | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
| Hypertension | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) |
AE adverse event, CI confidence interval, IFN interferon, MS multiple sclerosis, NA not applicable, OLE open-label extension, SAE serious adverse event
aTable of most common events excludes influenza-like illness reported during the primary treatment period only in 11 patients (20.4%) who received IFN β-1a. Doses in primary treatment and treatment-free periods refer to cycle 1 randomization. All patients received ocrelizumab in cycles 2–4 of the primary treatment period