TABLE 4

Serious adverse events registered during the treatment course among patients on standard and prolonged treatment with bedaquiline

Bedaquiline <190 daysBedaquiline>190 daysOverallp-value#
between standard and prolonged
Number of patients8330113
Total treatment duration months1807.8722.72530.5
Total treatment with bedaquiline months440.3257.2697.5
Total treatment up to 5 months after bedaquiline cessation, months836.5404.41240.9
Serious adverse events
 Patients experiencing any serious adverse event32 (38.6)16 (53.3)48 (42.5)
 Events during treatment total502676
  Incidence per 100 person-months (95% CI)2.8 (2.1–3.6)3.6 (2.4–5.3)3.0 (2.4–3.8)0.30
Serious adverse events during periods of treatment
 Events with bedaquiline up to day 190 of treatment371047
  Incidence per 100 person-months (95% CI)7.5 (5.5–10.0)5.4 (2.6–9.9)8.4 (5.9–11.6)0.07
 Events with bedaquiline from day 190 to cessationN/A00
  Incidence per 100 person-months (95% CI)N/A0 (0–5.2)0 (0–5.2)
 Events after stopping bedaquiline up to 5 months after bedaquiline cessation8816
  Incidence per 100 person-months (95% CI)2.0 (0.9–4.0)5.4 (2.3–10.7)2.9 (1.7–4.8)0.10
 Events > 5 months after stopping bedaquiline, to end of treatment5813
  Incidence per 100 person-months (95% CI)0.5 (0.2–1.2)2.5 (1.1–5.0)1.0 (0.5–1.7)0.03
 All events up to 5 months after stopping bedaquiline451863
  Incidence per 100 person-months (95% CI)5.4 (3.9–7.2)4.4 (2.6–7.0)5.1 (3.9–6.5)0.48
Bedaquiline-related serious adverse events
 Patients with at least one bedaquiline-related serious adverse event516
 Number of bedaquiline-related serious adverse events up to 5 months after bedaquiline cessation617
  Incidence per 100 person-months (95% CI)0.7 (0.3–1.6)0.2 (0.1–1.4)0.6 (0.2–1.2)0.22
 Category of serious adverse events
  QTcF prolongation2 (33.3)1 (100)3 (42.8)
  Liver enzyme elevation1 (16.7)0 (0)1 (14.3)
  Pancreatitis1 (16.7)0 (0)1 (14.3)
  Hyperuricaemia1 (16.7)0 (0)1 (14.3)
  Cardiac failure1 (16.7)0 (0)1 (14.3)
 Patients stopping treatment due to bedaquiline-related serious adverse event101
  Months to bedaquiline cessation1.4N/AN/A

Data reported as n (%) unless otherwise specified. #: exact Fisher two-sided test was used to calculate p-value; : patient experienced two serious adverse events: the first was hyperuricaemia 21 days into treatment and the second was aspartate aminotransferase elevation 147 days into treatment.