An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex^® (THC:CBD, nabiximols) oromucosal spray

Figures & data

Figure 1 Registry study design.

Notes: Showing the marketing authorization dates for the UK, Germany, and Switzerland, and the DCP windows. Data have been collected for UK patients from DCP1 to DCP9 inclusive; no further data will be collected from the UK following the closure of the UK Registry in January 2015. Data have been collected for German patients from DCP4 and for Swiss patients from DCP9; data will continue to be collected from these countries. Data for the same patient could be collected in multiple DCPs.
Abbreviation: DCP, data collection period.

Table 1 Patient demographics

Parameter	Statistic	All patients	Spasticity due to MS	Other indication
Age at start of THC:CBD (years)a	n	852	530	121
	Mean	51.2	51.5	48.5
	SD	10.82	10.02	13.50
	Median	51	51	47
	Min, Max	18, 85	22, 79	18, 85
Sex, n (%)	Female	540 (57)	338 (61)	49 (39)
	Male	401 (43)	216 (39)	76 (61)

Notes: Age (n=852) and sex (N=941) of all patients together and split according to indication.

a Age at start of THC:CBD use was not available for all patients; accordingly, only data from patients with this information are included in the table.

Abbreviations: CBD, cannabidiol; Max, maximum; Min, minimum; MS, multiple sclerosis; SD, standard deviation; THC, Δ⁹-tetrahydrocannabinol.

Figure 2 Patient duration of exposure to THC:CBD.

Note: Showing the duration of THC:CBD use for patients in the Registry split into discrete time periods (n=848).
Abbreviations: CBD, cannabidiol; d, days; m, months; THC, Δ⁹-tetrahydrocannabinol; y, years.

Table 2 Incidence rates for special interest events

Adverse event of special interest	Response	n (%)	Incidence ratea
Clinically significant AEs	Yes	216 (23)	0.098
	No/not recorded	725 (77)
Medical attention required due to fall-related injury	Yes	61 (6)	0.028
	No/not recorded	880 (94)
Other significant psychiatric or psychotic events	Yes	55 (6)	0.025
	No/not recorded	886 (94)
Suicidal thoughts or attempted suicide	Yes	15 (2)	0.007
	No/not recorded	926 (98)
Change in driving ability	Improved	63 (7)	0.028
	Deteriorated	19 (2)	0.009
	Both improved and deterioratedb	2 (0.2)	0.001
	No change	303 (32)
	Not appropriate	514 (55)
	Not recorded	40 (4)

Notes:

a Per year of THC:CBD exposure, calculated by dividing the number of patients reporting the AE of special interest by the total patient-years of THC:CBD exposure in the Registry (2,213.98 years).

b Improvement and deterioration reported at different DCPs.

Abbreviations: AE, adverse event; CBD, cannabidiol; DCP, data collection period; THC, Δ⁹-tetrahydrocannabinol.

Table 3 Most commonly reported AEs

MedDRA SOC	Patients with at least one AE (N=941)
MedDRA preferred term	All causality	Treatment relateda
	n (%)	n (%)	Incidence rateb
All SOCs	295 (31.3)	123 (13.1)	0.0556
Nervous system disorders	117 (12.4)	55 (5.8)	0.0248
Dizziness	29 (3.1)	22 (2.3)	0.0099
Multiple sclerosis	17 (1.8)	1 (0.1)	0.0005
Multiple sclerosis relapse	15 (1.6)	1 (0.1)	0.0005
Somnolence	10 (1.1)	8 (0.9)	0.0036
Dysgeusia	9 (1.0)	9 (1.0)	0.0041
Psychiatric disorders	68 (7.2)	27 (2.9)	0.0122
Depression	27 (2.9)	3 (0.3)	0.0014
Anxiety	9 (1.0)	5 (0.5)	0.0023
Depressed mood	10 (1.1)	5 (0.5)	0.0023
Gastrointestinal disorders	57 (6.1)	32 (3.4)	0.0144
Nausea	15 (1.6)	10 (1.1)	0.0045
Injury, poisoning, and procedural complications	56 (6.0)	6 (0.6)	0.0027
Fall	51 (5.4)	6 (0.6)	0.0027
General disorders and administration site conditions	50 (5.3)	26 (2.8)	0.0117
Fatigue	20 (2.1)	16 (1.7)	0.0072
Infections and infestations	37 (3.9)	1 (0.1)	0.0005
Urinary tract infection	12 (1.3)	1 (0.1)	0.0005

Notes: Showing all (all-causalities) AEs with ≥1% incidence by SOC and preferred term, and the corresponding treatment-related rates.

a Causality as assigned by prescriber; does not include instances where causality was not provided.

b Per year of THC:CBD exposure, calculated by dividing the number of patients reporting the AE by the total patient-years of THC:CDB exposure in the Registry (2,213.98 years). The bold entries denote the SOC, the nonbold text beneath each are preferred terms within that SOC.

Abbreviations: AE, adverse event; CBD, cannabidiol; MedDRA, Medical Dictionary for Regulatory Activities; SOC, system organ class; THC, Δ⁹-tetrahydrocannabinol.

Table 4 AEs presented by incidence and time to first onset category

Time category	≤28 d	29 d–6 m	6–12 m	12–18 m	18–24 m	>2 y	Unknowna
Total number of patients	941	783	626	523	457	408	941
Patients reporting any AE, n (%)	77 (8.2)	26 (3.3)	30 (4.8)	9 (1.7)	6 (1.3)	52 (12.7)	95 (10.1)

Note:

a AE reported, but no time of onset information provided.

Abbreviations: AE, adverse event; d, days; m, months; y, years.

Table 5 Most commonly reported SAEs

MedDRA SOC	Patients with at least one SAE (N=941)
MedDRA preferred term	All causality	Treatment relateda		Missing causality
	n (%)	n (%)	Incidence rateb	n (%)
All SOCs	113 (12.0)	24 (2.6)	0.0108	11 (1.2)
Nervous system disorders	34 (3.6)	7 (0.7)	0.0032	3 (0.3)
Multiple sclerosis	11 (1.2)	0	N/A	1 (0.1)
Multiple sclerosis relapse	8 (0.9)	1 (0.1)	0.0005	0
Psychiatric disorders	24 (2.6)	6 (0.6)	0.0027	0
Depression	9 (1.0)	1 (0.1)	0.0005	0
Infections and infestations	22 (2.3)	0	N/A	2 (0.2)
Pneumonia	8 (0.9)	0	N/A	2 (0.2)
Injury, poisoning, and procedural complications	20 (2.1)	4 (0.4)	0.0018	3 (0.3)
Fall	18 (1.9)	4 (0.4)	0.0018	2 (0.2)
Neoplasms benign, malignant, and unspecified	14 (1.5)	2 (0.2)	0.0009	0
Gastrointestinal disorders	12 (1.3)	5 (0.5)	0.0023	0

Notes: Showing all SAEs by SOC (≥1% incidence) and preferred term (≥0.5%), and the corresponding treatment-related and missing causality rates.

a Causality as assigned by prescriber; does not include instances where causality was not provided.

b Per year of THC:CBD exposure, calculated by dividing the number of patients reporting the SAE by the total patient-years of THC:CBD exposure in the Registry (2,213.98 years). The bold entries denote the SOC, the nonbold text beneath each are preferred terms within that SOC.

Abbreviations: CBD, cannabidiol; MedDRA, Medical Dictionary for Regulatory Activities; N/A, not applicable; SAE, serious adverse event; SOC, system organ class; THC, Δ⁹-tetrahydrocannabinol.