Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

Figures & data

Figure 1 Study design, highlighting the conversion and titration phase.

Abbreviation: ER, extended release.

Table 1 Demographic and baseline characteristics

Characteristic	OROS hydromorphone ER (N = 447)
Age, years
Mean (SD)	49.0 (10.43)
Age group, n (%)
18–64 years	420 (94.0)
65–75 years	27 (6.0)
Sex, n (%)
Male	227 (50.8)
Race, n (%)
Caucasian	383 (85.7)
Black	37 (8.3)
Other	27 (6.0)
Weight, kg
Mean (SD)	90.33 (23.35)
Height, cm
Mean (SD)	170.95 (10.75)
Body mass index, kg/m^2
Mean (SD)	30.85 (7.36)
Etiology, n (%)
Non-neuropathic low back paina	276 (61.7)
Neuropathic low back painb	167 (37.4)
Missing	4 (0.9)
Prior opioid, n (%)
Hydrocodone	151 (33.8)
Oxycodone	123 (27.5)
Morphine	73 (16.3)
Fentanyl	26 (5.8)
Methadone	25 (5.6)
Tramadol	22 (4.9)
Propoxyphene	8 (1.8)
Hydromorphone	8 (1.8)
Oxymorphone	7 (1.6)

Notes:

a Class 1 or 2 based on the Quebec Task Force Classification of Spinal Disorders;

b class 3, 4, 5, or 6 based on the Quebec Task Force Classification of Spinal Disorders.

Abbreviations: ER, extended release; N, total number; SD, standard deviation.

Table 2 Patients with response by prior opioid compound

Prior opioid compound	OROS hydromorphone ER n/N (%)
Hydromorphone	6/8 (75.0)
Fentanyl	19/26 (73.1)
Tramadol	15/22 (68.2)
Hydrocodone	95/151 (62.9)
Morphine	42/73 (57.5)
Methadone	14/25 (56.0)
Oxycodone	68/123 (55.3)
Propoxyphene	4/8 (50.0)
Oxymorphone	3/7 (42.9)
Missing data	2/4 (50.0)

Abbreviations: ER, extended release; n, number; N, total number.

Table 3 Duration of exposure

Duration of exposure	OROS hydromorphone ER (N = 447)
Duration, daysa
Mean (SD)	20.1 (9.58)
Median (range)	22.0 (1–49)
Duration rangeb, n (%)
<1 week	34 (7.6)
1 to <2 weeks	75 (16.8)
2 to <3 weeks	97 (21.7)
3 to <4 weeks	107 (23.9)
≥4 weeksc	134 (30.0)

Notes:

a Duration in days calculated as the difference between the first date medication was dispensed and the date of the last dose in the conversion and titration phase;

b duration in weeks calculated as the difference between the first date medication was dispensed and the date of the last dose in the conversion and titration phase divided by seven;

c last office visit, if necessary, occurred at week 4/day 29.

Abbreviations: ER, extended release; N, total number; SD, standard deviation.

Figure 2 Distribution of initial and final doses of OROS hydromorphone ER in patients who achieved an effective dose.

Abbreviation: ER, extended release.

Table 4 Most common adverse events in the safety population (>5%) overall and according to achievement of a stable dose

Adverse event, n (%)	Safety population (N = 447)	Achieved a stable dose (n = 268)	Did not achieve stable dose (n = 179)
Any adverse event	247 (55.3)	139 (51.9)	108 (60.3)
Constipation	69 (15.4)	43 (16.0)	26 (14.5)
Nausea	53 (11.9)	27 (10.1)	26 (14.5)
Somnolence	39 (8.7)	21 (7.8)	18 (10.1)
Headache	35 (7.8)	19 (7.1)	16 (8.9)
Vomiting	29 (6.5)	13 (4.9)	16 (8.9)

Abbreviations: n, number; N, total number.

Table 5 Summary of all AEs by OROS hydromorphone ER dose (safety population)

Evaluationa	OROS hydromorphone ER doseb
	12 mg (n = 192)	16 mg (n = 268)	24 mg (n = 265)	32 mg (n = 235)	40 mg (n = 200)	48 mg (n = 167)	64 mg (n = 103)
Patients with any AE, n (%)	47 (24.5)	67 (25.0)	80 (30.2)	59 (25.1)	44 (22.0)	43 (25.7)	30 (29.1)
Patients with any SAEc, n (%)	1 (0.5)	0 (0.0)	5 (1.9)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Discontinuation due to AEs, n (%)	8 (4.2)	9 (3.4)	13 (4.9)	8 (3.4)	9 (4.5)	8 (4.8)	1 (1.0)
Total number of AEsd, n	85	121	203	132	88	99	52

Notes:

a An AE may be counted multiple times for an individual patient under these circumstances: dose at onset of AE and dose at the time the AE increased in intensity;

b n is the number of patients who were exposed to each dose;

c an AE of headache for Patient 018019 was marked as a serious AE;

d each occurrence of an AE is counted (eg, multiple occurrences of the same AE in one patient are counted as multiple AEs).

Abbreviations: AE, adverse event; ER, extended release; n, number; SAE, serious adverse event.

Figure 3 Adverse events of constipation, by history of constipation and prophylaxis.

Note: *Prophylactic treatment for constipation included osmotic laxatives and peristalsis-increasing agents.
Abbreviations: N, total number; n, number.