Serious adverse events and adverse events occurring in at least 5% of the patients by treatment group for events
| Adverse events* | Part 1† | Part 2‡ | All-exposure safety group§ N=188 | |
|---|---|---|---|---|
| Tocilizumab N=188 | All tocilizumab n=82 | All placebo‡ n=81 | ||
| Duration in study (years) | 59.92 | 32.33 | 27.41 | 184.4 |
| Patients with at least one AE | 124 (66.0) | 58 (70.7) | 60 (74.1) | 159 (84.6) |
| Total number of AEs¶ | 365 | 147 | 141 | 885 |
| Rate of AEs per 100 PY** | 609.2 | 454.7 | 514.4 | 479.8 |
| Most frequently reported (>5%) AEs | ||||
| Nasopharyngitis | 23 (12.2) | 14 (17.1) | 9 (11.1) | 39 (20.7) |
| Headache | 15 (8.0) | 3 (3.7) | – | 26 (13.8) |
| Upper respiratory infection | 13 (6.9) | 4 (4.9) | 2 (2.5) | 19 (10.1) |
| Cough | 7 (3.7) | 2 (2.4) | 1 (1.2) | 18 (9.6) |
| Pharyngitis | 8 (4.3) | 3 (3.7) | 3 (3.7) | 17 (9.0) |
| Nausea | 12 (6.4) | 2 (2.4) | 2 (2.5) | 16 (8.5) |
| Diarrhoea | 7 (3.7) | 2 (2.4) | 3 (3.7) | 14 (7.4) |
| Rhinitis | 7 (3.7) | 2 (2.4) | 1 (1.2) | 14 (7.4) |
| Vomiting | 4 (2.1) | 3 (3.7) | 1 (1.2) | 14 (7.4) |
| Abdominal pain | 5 (2.7) | 2 (2.4) | 2 (2.5) | 13 (6.9) |
| Oropharyngeal pain | 8 (4.3) | 1 (1.2) | 5 (6.2) | 13 (6.9) |
| Rash | 3 (1.6) | 4 (4.9) | 1 (1.2) | 10 (5.3) |
| SAEs | ||||
| Patients with at least one SAE | 7 (3.7) | 3 (3.7) | 3 (3.7) | 17 (9.0) |
| Rate of SAEs per 100 PY | 13.4 | 9.3 | 10.9 | 12.5 |
| Patients with at least one infectious SAE | 4 (2.1) | 1 (1.2) | – | 9 (4.8) |
| Rates of infectious SAEs per 100 PY | 6.7 | 3.1 | – | 4.9 |
| SAEs by preferred term | – | |||
| Pneumonia | 1 (0.5) | 1 (1.2) | – | 4 (2.1) |
| Bronchitis | 2 (1.1) | – | – | 2 (1.1) |
| Cellulitis | 1 (0.5) | – | – | 2 (1.1) |
| Varicella | – | – | – | 1 (0.5) |
| Neck injury | – | – | – | 1 (0.5) |
| Synovial rupture | – | – | – | 1 (0.5) |
| Upper limb fracture | – | 1 (1.2) | – | 1 (0.5) |
| Sclerosing cholangitis | 1 (0.5) | – | – | 1 (0.5) |
| Hypertransaminasemia | 1 (0.5) | – | – | 1 (0.5) |
| Back pain | – | – | – | 1 (0.5) |
| Osteoporosis | – | – | –— | 1 (0.5) |
| Familial Mediterranean fever†† | – | – | – | 1 (0.5) |
| Uveitis | – | – | 1 (1.2) | 1 (0.5) |
| Constipation | 1 (0.5) | – | – | 1 (0.5) |
| Benign intracranial hypertension | 1 (0.5) | – | – | 1 (0.5) |
| Psychosomatic disease | – | 1 (1.2) | – | 1 (0.5) |
| Urinary calculus | – | – | – | 1 (0.5) |
| Enterocolitis | – | – | 1 (1.2) | |
| Complicated migraine | – | – | 1 (1.2) | |
| AEs leading to study drug discontinuation | – | |||
| Increased blood bilirubin level‡‡ | – | 1 (1.2) | – | 1 (0.5) |
| Serum sickness-like reaction§§ | 1 (0.5) | – | – | 1 (0.5) |
| Gastroenteritis | – | – | 1 (1.2) | 1 (0.5)*** |
| Pneumonia | 1 (0.5) | – | – | 1 (0.5) |
| Sclerosing cholangitis¶¶ | 1 (0.5) | – | – | 1 (0.5) |
| Benign intracranial hypertension | 1 (0.5) | – | – | 1 (0.5) |
Values are n (%) unless stated otherwise.
*Multiple occurrences of the same AE in one individual were counted only once, except where noted.
†Sixteen-week, open-label, lead-in part 1 with all patients receiving tocilizumab.
‡Both groups received tocilizumab open-label during part 1 before entering part 2 (24-week withdrawal phase). AE data on open-label tocilizumab escape therapy were excluded.
§Summarises all AEs except those that occurred in a patient once on placebo and includes data after week 40 because safety was based on the data cut.
¶Multiple occurrences of the same AE in one individual were counted.
**Patient-year.
††Recurrence in patient with pcJIA, with flare of familial Mediterranean fever.
‡‡Highest total bilirubin reading, 50 μmol/L (normal range, 3–24 μmol/L); two consecutive readings >51 mmol/L mandated withdrawal per protocol. The event resolved without sequelae.
§§Patient with serum sickness-like reaction and subcutaneous swelling on dorsum of hand, forearm and foot; the patient was discontinued from the study.
¶¶The patient had transaminitis on study entry: 139 U/L aspartate aminotransferase, 147 U/L alanine aminotransferase; highest readings: 287 U/L aspartate aminotransferase, 289 U/L alanine aminotransferase. Liver biopsy was performed on study day 134; results were compatible with sclerosing cholangitis. The event was unresolved and considered unrelated to study medication.
***Occurred 46 days after the last of five doses of placebo.
AE, adverse event; JIA, juvenile idiopathic arthritis; PY, patient-years; SAE, serious adverse event.