Table 3.
Adverse Events and Serious Adverse Events.
| Variable | Teprotumumab (N = 43)* | Placebo (N = 44)* | Summary Details of Adverse Events in Teprotumumab Group |
|---|---|---|---|
| number of patients (percent) | |||
| Adverse event during intervention† | |||
| Nausea | 8 (19) | 4 (9) | Generally mild and reported after first and second infusions |
| Muscle spasms | 8 (19) | 2 (5) | Intermittent, 2 of 8 patients had muscle spasms for >1 wk and received muscle relaxants |
| Diarrhea | 6 (14) | 2 (5) | Treatment occurred in 2 of 6 patients, 1 case designated as a serious adverse event (see below) |
| Hyperglycemia | 5 (12) | 2 (5) | Mechanism-based adverse event |
| Alopecia | 3 (7) | 2 (5) | All mild and no treatment necessary |
| Dry skin | 3 (7) | 0 | All mild, 1 patient used topical dry-skin cream |
| Dysgeusia | 3 (7) | 0 | In 2 of 3 patients, a transient “metallic” taste reported on days 1–2 |
| Headache | 3 (7) | 2 (5) | Generally mild, 1 patient took paracetamol |
| Paresthesia | 3 (7) | 0 | “Tingling” reported in nose, feet, or chest; variable onset and in 2 of 3 patients occurred on 1 day |
| Hearing impairment | 3 (7) | 0 | Disparate symptoms, onset, and duration (i.e., one case of unilateral hearing impairment with onset 16 wk after end of therapy, ‡ one case of mild bilateral hearing impairment that resolved, and one case of tinnitus in a patient with a history of tinnitus) |
| Weight loss | 3 (7) | 0 | Variable timing; decreases ranged from 5–9 lb (11–20 kg) |
| Any adverse event during intervention | 32 (74) | 32 (73) | |
| Serious adverse event§ | |||
| Optic neuropathy¶ | 0 | 1 (2) | |
| Diarrhea | 1 (2) | 0 | Severe diarrhea in 1 patient with a 6-mo history of ulcerative colitis |
| Inflammatory bowel disease | 1 (2) | 0 | In 1 patient with recent diagnosis of ileitis and colitis, inflammatory bowel disease diagnosed and treated while patient received trial drug |
| Escherichia sepsis║ | 1 (2) | 0 | Escherichia coli infection of unknown origin treated with intravenous antibiotics |
| Hashimoto’s encephalopathy | 1 (2) | 0 | Provisional diagnosis after episodic mental confusion with no other neurologic symptoms |
| Urinary retention | 1 (2) | 0 | Diagnosed after patient had an inguinal herniorrhaphy |
| Any serious adverse event | 5 (12) | 1 (2) | |
One patient in the placebo group received a single dose of teprotumumab in error at week 15. That patient is included here in the teprotumumab group.
Adverse events of any cause were defined as those that occurred between the administration of the first dose and 30 days after the administration of the final dose. Listed adverse events that emerged during the intervention phase are those that occurred in more than 5% of patients in the teprotumumab group and that occurred in greater numbers in the teprotumumab group than in the placebo group. Patients may have had more than one adverse event.
This case is included because the patient had unrelated, transient eustachian-tube dysfunction while receiving teprotumumab.
Listed are all serious adverse events reported in the trial, including any adverse event involving hospitalization. In the teprotumumab group, four patients discontinued the intervention because of the following serious adverse events: diarrhea that occurred after six infusions, inflammatory bowel disease after seven, Escherichia coli sepsis after three, and Hashimoto’s encephalopathy after six.
A total of three patients in the placebo group withdrew from the trial because of worsening eye symptoms or a lack of response. One case of dysthyroid optic neuropathy designated by an investigator as a serious adverse event occurred 3 days after the week 24 evaluation.
This patient was the only one whose intervention was unmasked during the course of the trial.