Sick Leave and Costs in Active Workers with Chronic Osteoarthritis Pain in Spain: Outcomes of the OPIOIDS Real World Study

Figures & data

Table 1 Baseline Characteristics (Demographic and Morbidity) of Patients by Study Groups

Study Groups	Weak Opioid	Strong Opioid	Total	p-value
Number of patients	3732 (73.3%)	1357 (26.7%)	5089 (100%)
Demographic features
Mean age, years (SD)	56.8 (4.6)	56.8 (4.7)	56.8 (4.6)	0.848
Age group: 18–44 years	1.4%	1.4%	1.4%
45–54 years	33.8%	33.2%	33.6%
≥ 55 years	64.8%	65.4%	65.0%	0.912
Sex (female)	56.2%	57.5%	56.6%	0.431
General comorbidity
Mean number of comorbidities (SD)	2.3 (1.5)	2.4 (1.6)	2.4 (1.6)	0.032
Mean Charlson index (SD)	1.1 (0.3)	1.2 (0.3)	1.1 (0.3)	0.041
0	44.6%	47.5%	45.4%
1	27.5%	22.5%	26.2%
2	13.8%	16.0%	14.4%
3+	6.0%	6.6%	6.2%	0.066
Associated comorbidities
High blood pressure	39.8%	39.1%	39.6%	0.683
Diabetes	16.6%	16.9%	16.7%	0.807
Dyslipidemia	55.3%	52.5%	54.5%	0.078
Obesity	29.0%	23.0%	27.4%	<0.001
Ischemic heart disease	4.5%	4.3%	4.5%	0.783
Cerebrovascular event	2.8%	3.8%	3.1%	0.084
Heart failure	1.8%	2.9%	2.1%	0.017
Kidney failure	1.9%	1.8%	1.9%	0.710
Asthma	11.3%	11.3%	11.3%	0.967
COPD	7.2%	7.8%	7.3%	0.426
Dementia	1.3%	2.3%	1.6%	0.017
Depressive syndrome	20.3%	23.3%	21.1%	0.023
Anxiety	46.8%	50.6%	47.8%	0.018
Malignancies	5.8%	5.4%	5.7%	0.554
Osteoporosis	19.6%	21.9%	20.2%	0.071
Lifestyle
Active smokers (daily)	23.6%	27.7%	24.7%	0.003
Alcohol consumption ≥30 grams/day	2.8%	2.4%	2.7%	0.521
Osteoarthritis site
Knee/hip	49.8%	49.4%	49.7%
Spine	31.5%	32.1%	31.7%
Others	18.6%	18.6%	18.6%	0.939

Note: Values expressed as percentage or mean (SD).

Abbreviations: %, percentage; COPD, chronic obstructive pulmonary disease; SD, standard deviation.

Figure 1 Study flow diagram.

Abbreviation: NRS, numeric rating scale.

Table 2 Treatment Persistence and Adherence, Medication Possession Ratio and Discontinuation by Study Groups

Study Groups	Weak Opioid	Strong Opioid	Total	p-value
Number of patients	3732 (73.3%)	1357 (26.7%)	5089 (100%)
Time from diagnosis, years	3.4 (1.0)	3.5 (1.2)	3.4 (1.1)	0.002
- Median (P25 - P75)	2.9 (2.7–3.9)	2.9 (2.7–3.8)	2.9 (2.7–3.9)
Duration of treatment, days	427 (417.4)	343.4 (372.9)	404.7 (407.7)	<0.001
- Median (P25 - P75)	201 (84–890)	155 (83–467)	187 (84–738)
Medication possession ratio
Percentage	74.0%	69.2%	72.7%	<0.001
95% CI	72.6–75.4%	66.7–71.7%	71.5–73.9%
Treatment adherence
12 months	38.6%	29.0%	36.0%	<0.001
95% CI	37.0–40.2%	26.6–31.4%	34.7–37.3%
24 months	27.4%	18.6%	25.1%	<0.001
95% CI	26.0–28.8%	16.5–20.7%	23.9–26.3%
36 months	23.0%	15.4%	21.0%	<0.001
95% CI	21.6–24.4%	13.5–17.3%	19.9–22.1%
Discontinuation	77.0%	84.6%	79.0%	<0.001
Poor tolerability*	11.8%	8.7%	10.9%	0.004
95% CI	10.8–12.8%	7.2–10.2%	10.0–11.8%
Poor response**	48.2%	60.4%	51.7%	<0.001
95% CI	46.6–49.8%	57.8–63.0%	50.3–53.1%
Change from weak to strong opioid	17.3%	NA	NA	NA
95% CI	16.1–18.5%
Other changes***	12.5%	21.3%	15.0%	<0.001
95% CI	11.4–13.6%	19.1–23.5%	14.0–16.0%
Lost-to-follow up	10.1%	9.6%	10.0%	0.601
95% CI	9.1–11.1%	8.8–11.2%	9.2–10.8%
Any cause deaths	1.1%	3.1%	1.7%	<0.001
95% CI	0.8–1.4%	2.2–4.0%	1.3–2.1%

Notes: Values expressed as percentage or mean (SD, CI), or median (P25-P75). *Discontinuation after 1st prescription dispensed in community pharmacy without refills during study follow-up; **Pain numeric rating scale ≥ 5 points in last available measurement; ***Other changes: includes patients with hospital admission for surgical procedures (joint replacement, arthroscopy, 2.6%), referrals to the pain clinic (1.3%) and changes in non-opioid medication (0.9%).

Abbreviations: %, percentage; CI, confidence interval; NA, not applicable; P, percentile.

Table 3 Days of Sick Leave and Annual Cost Due to Lost Productivity

Study Groups	Weak Opioid	Strong Opioid	Total	p-value
Number of patients	3732 (73.3%)	1357 (26.7%)	5089 (100%)
12-month pre-opioid period
Patients with sick leave	33.4%	34.5%	33.7%	0.452
Ranges according to days of sick leave
1–7 days	15.3%	13.7%	14.9%
8–14 days	18.6%	11.5%	16.7%
15–89 days	51.9%	56.8%	53.2%
90–181 days	11.0%	13.9%	11.8%
≥ 182 days (6 months)	3.1%	4.1%	3.4%	0.003
Days of sick leave in patients with sick leave	49.9 (48.6)	59.6 (52.4)	52.6 (49.8)	<0.001
Days of sick leave in all patients	16.6 (36.6)	20.6 (41.8)	17.7 (38.1)	0.001
Cost/year for patient with sick leave (€)	5960 (5804)	7122 (6258)	6277 (5952)	<0.001
Cost/year for patient (all., €)	1988 (4374)	2456 (4996)	2113 (4552)	0.001
12-month post-opioid initiation period
Patients with sick leave	38.2%	37.4%	37.9%	0.605
Ranges according to days of sick leave
1–7 days	9.5%	4.7%	8.2%
8–14 days	15.3%	10.7%	14.1%
15–89 days	59.1%	63.1%	60.1%
90–181 days	10.5%	14.2%	11.5%	0.160
≥ 182 days (6 months)	5.6%	7.3%	6.1%	0.001
Days of sick leave in patients with sick leave	54.6 (54.1)	64.2 (58.1)	57.1 (55.3)	0.004
Days of sick leave in all patients	20.9 (42.7)	24.0 (47.2)	21.7 (43.9)	0.027
Cost/year for patient with sick leave (€)	6541 (6458)	7666 (6939)	6837 (6604)	0.004
Cost/year for patient (all., €)	2496 (5100)	2864 (5633)	2594 (5249)	0.027
Variations in 12 months before and 12 months after opioid initiation
Patients with sick leave (%, 95% CI)	4.8% (4.1–5.5)^‡	2.9% (2.0–3.8)^‡	4.3% (3.7–4.9)^‡	0.007
Days of sick leave in patients with sick leave	4.7 (3.1–6.3)^‡	4.6 (2.6–6.6)^‡	4.5 (2.6–6.4)^‡	0.654
Days of sick leave in all patients	4.3 (2.5–6.1)^‡	3.4 (0.2–5.8)*	4.0 (2.4–5.6)^‡	0.455
Cost/year for patient with sick leave (€)	581 (578–585)^‡	544 (539–548)*	559 (556–561)^‡	<0.001
Cost/year for patient (all., €)	508 (458–555)^‡	408 (326–489)*	481 (439–522)^‡	<0.001
36-month post-opioid initiation period
Patients with sick leave	77.6%	75.5%	77.0%	0.109
Range/ intervals
1–7 days	4.9%	0.5%	3.8%
8–14 days	11.6%	2.2%	9.2%
15–89 days	63.7%	66.4%	64.4%
90–181 days	3.1%	13.5%	5.8%
≥ 182 days (6 months)	16.7%	17.4%	16.9%	<0.001
Days of sick leave in patients with sick leave	115.5 (179.1)	134.5 (188.8)	120.5 (181.8)	0.004
Days of sick leave in all patients	89.8 (165.2)	101.6 (173.9)	93.0 (167.6)	0.026
Cost/year for patient with sick leave (€)	13,823 (21,421)	16,084 (22,548)	14,414 (21,741)	0.004
Cost/year for patient (all., €)	10,727 (19,731)	12,137 (20,773)	11,103 (20,021)	0.026
Sick leaves during follow up
0 (none)	22.4%	24.5%	23.0%
1	35.9%	29.9%	34.3%
2	24.2%	29.4%	25.6%
3+	17.5%	16.1%	17.2%	<0.001

Notes: Values expressed as percentage or mean (95% CI), mean (95%) cost expressed in €. ^‡p<0.001; *p<0.05. Non-significant when not indicated.

Abbreviations: all, all patients; CI, confidence interval.

Table 4 Mean Adjusted Productivity Costs (€/Patient) During the Follow-Up Period in Different Scenarios

Scenario	Cost/Patient-Year* (95% CI)	Difference (95% CI)	p-value
Site of osteoarthritis
Knee/hip	11,576 (10,609–12,544)	vs Spine: 874 (−1029–2777)	0.869
Spine	10,702 (9480–11,923)	vs other: 360 (−2620–1901)	0.781
Other	11,936 (10,359–13,513)	vs other: 1234 (−2578–110)	0.517
Type of opioid
Weak opioid	10,987 (10,218–11,756)
Strong opioid	12,516 (10,985–14,048)	1529 (188–3255)	0.044
Pain reduction (initial vs final)
Relative reduction in baseline pain ≥30%	11,265 (10,532–11,998)
Relative reduction in baseline pain <30%	11,983 (10,081–13,885)	718 (−1318–2754)	0.491
Relative reduction in baseline pain ≥50%	11,141 (10,432–11,851)
Relative reduction in baseline pain <50%	14,016 (11,471–16,561)	2875 (232–5518)	0.033
Pain in last record ≥5 in NRS	11,282 (10,572–11,993)
Pain in last record <5 in NRS	12,226 (9670–14,783)	944 (−1092–2262)	0.459
Combinations of NSAIDs + opioids
Without NSAID + weak opioid	10,724 (9872–11,578)
Without NSAID + strong opioid	12,258 (10,645–13,872)	1534 (188–2881)	0.042
With NSAID + weak opioid	10,729 (9783–11,675)
With NSAID + strong opioid	12,018 (10,498–13,538)	1289 (57–2635)	0.046
Multiple linear regression model	Standardized coefficients (β)	t	p
Age, years	0.043	2.960	0.003
Sex (female)	0.036	2.500	0.011
Charlson index (comorbidity)	0.035	2.440	0.015
Strong opioid	0.031	2.244	0.025

Notes: Values expressed as percentage or mean (95% CI). *Analysis of covariance (ANCOVA; procedure: estimate of marginal means; Bonferroni adjustment), for adjustment of cost per patient of days of sick leave. Covariates: age, sex, time from diagnosis, Charlson index, treatment persistence and relative reduction in pain).

Abbreviations: β, standardized coefficient; CI, confidence intervals; NRS, numeric rating scale of pain; NSAID, nonsteroidal anti-inflammatory drug; t, Student’s t test; vs, versus.

Figure 2 Mean cost per patient (€) of sick leaves adjusted by covariates during follow up (36 months) by sex (A) and age group (B).

Notes: Values expressed as means. *p <0.05 (reference cohort: females and 55+ years, respectively). Not significant when not indicated.