Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database

Figures & data

Table 1 Demographic characteristics of cases and controls by analysis

	Cataract				Glaucoma
	Cases (N = 2404)		Controls (N = 5621)		Cases (N = 273)		Controls (N = 703)
	N	(%)	N	(%)	N	(%)	N	(%)
Age at indexa
45–49	0	0	2	(0.04)	–	–	–	–
50–54	8	(0.3)	22	(0.4)	3	(1.1)	8	(1.1)
55–59	54	(2.3)	129	(2.3)	9	(3.3)	20	(2.8)
60–64	122	(5.1)	329	(5.9)	24	(8.8)	54	(7.7)
65–69	284	(11.8)	781	(13.9)	44	(16.1)	126	(17.9)
70–74	472	(19.6)	1220	(21.7)	61	(22.3)	159	(22.6)
75–79	697	(29)	1674	(29.8)	66	(24.2)	179	(25.5)
80–85	653	(27.2)	1274	(22.7)	54	(19.8)	138	(19.6)
≥86	114	(4.7)	190	(3.4)	12	(4.4)	19	(2.7)
Gender
Female	1235	(51.4)	2793	(49.7)	143	(52.4)	357	(50.8)
Male	1169	(48.6)	2828	(50.3)	130	(47.6)	346	(49.2)
BMI
Missing	1203	(50.0)	2958	(52.6)	138	(50.6)	366	(52.1)
10–18.49	82	(3.4)	185	(3.3)	4	(1.5)	23	(3.3)
18.50–24.99	435	(18.1)	963	(17.1)	56	(20.5)	111	(15.7)
25–29.99	382	(15.9)	881	(15.7)	39	(14.3)	109	(15.5)
30–70	302	(12.6)	634	(11.3)	36	(13.2)	94	(13.4)
Smoking status
Nonsmoker	348	(14.5)	743	(13.2)	31	(11.4)	91	(12.9)
Ex-smoker	1112	(46.3)	2437	(43.4)	120	(44)	292	(41.5)
Smoker	493	(20.5)	1324	(23.6)	69	(25.3)	186	(26.5)
Unknown	451	(18.8)	1117	(19.9)	53	(19.4)	134	(19.1)
Comorbid conditions
Vertebral fracture	11	(0.5)	24	(0.4)	2	(0.7)	3	(0.4)
Depression	120	(5)	228	(4.1)	12	(4.4)	38	(5.4)
Diabetes	350	(14.6)	538	(9.6)	23	(8.4)	76	(10.8)
Rheumatoid arthritis	11	(0.5)	40	(0.7)	0	0	5	(0.7)
Asthma	276	(11.5)	625	(11.1)	35	(12.8)	75	(10.7)
Osteoporosis	53	(2.2)	112	(1.2)	7	(2.6)	11	(1.6)
Stroke	38	(1.6)	74	(1.3)	4	(1.5)	10	(1.4)
Anemia	90	(3.7)	184	(3.3)	5	(1.8)	20	(2.8)
Osteopenia	13	(0.5)	26	(0.5)	1	(0.4)	5	(0.7)
Back pain	307	(12.8)	627	(11.2)	40	(14.7)	86	(12.2)
Falls	137	(5.7)	247	(4.4)	14	(5.1)	31	(4.4)
Hyperparathyroid	4	(0.2)	4	(0.1)	0	0	1	(0.14)
Dementia	9	(0.4)	28	(0.5)	2	(0.7)	7	(1.0)
Hypertension	364	(15.1)	946	(16.8)	47	(17.2)	115	(16.4)
Dyslipidemia	114	(4.7)	243	(4.3)	15	(5.5)	20	(2.84)
Obesity	306	(12.7)	639	(11.4)	36	(13.2)	95	(13.5)
Antibiotic: number of scripts in the previous year
None	723	(30.1)	1907	(34)	83	(30.4)	245	(34.9)
1	440	(18.3)	1257	(22.4)	63	(23.1)	154	(21.9)
2	344	(114.3)	832	(14.8)	37	(13.6)	100	(14.2)
3–4	434	(18.1)	876	(15.6)	41	(15.0)	125	(17.8)
≥5	463	(19.3)	749	(13.3)	49	(18)	79	(11.2)
Number of COPD visits
None	549	(22.9)	1366	(24.3)	75	(27.5)	185	(26.3)
1	990	(41.2)	2385	(42.4)	104	(38.1)	277	(39.4)
2	386	(16.1)	968	(17.2)	47	(17.2)	113	(16.1)
3+	479	(19.9)	902	(16.1)	47	(17.2)	128	(18.2)
Number of COPD hospitalizations
None	2189	(91.1)	5306	(94.4)	254	(93.0)	662	(94.2)
1	167	(7)	252	(4.5)	15	(5.5)	33	(4.7)
2+	48	(2.0)	63	(1.1)	4	(1.5)	8	(1.1)
Comedications
FSC	799	(33.2)	1655	(29.4)	78	(28.6)	226	(32.2)
ICS-containing product	1823	(75.8)	3961	(70.5)	197	(72.2)	510	(72.6)
BDP-containing product	847	(35.2)	1990	(35.4)	90	(33)	223	(31.7)
BUD-containing product	350	(14.6)	663	(11.8)	43	(15.8)	95	(13.5)
FP-containing product	898	(37.4)	1864	(33.2)	88	(32.2)	253	(36)
Oral corticosteroids	1098	(45.7)	2128	(37.9)	119	(43.6)	264	(37.6)
Antibiotic	1681	(69.9)	3714	(66.1)	190	(69.6)	458	(65.2)
Statin	850	(35.4)	1763	(31.4)	76	(27.8)	210	(29.9)
Nebulizer	476	(19.8)	761	(13.5)	51	(18.7)	92	(13.1)
Other respiratory product	1369	(56.9)	2827	(50.3)	146	(53.5)	359	(51.1)
Oxygen	160	(6.7)	268	(4.8)	15	(5.5)	45	(6.4)
Tiotropium-only product	616	(25.6)	1224	(21.8)	57	(20.9)	164	(23.3)
SABD-containing product	2156	(89.7)	4898	(87.1)	229	(83.9)	603	(85.8)
SABD with ICS product	0	0	3	(0.1)	NA	NA	NA	NA
ICS-containing product excluding FSC	1260	(52.4)	2799	(49.8)	136	(49.8)	338	(48.1)

Notes: Population includes patients with COPD in the GPRD between 2003 and 2006. Controls matched to cases on gender, age within 2 years, general practice, and number of years in the cohort prior to the event of interest.

a Index date is the date of the incident case of cataract or glaucoma and matched control.

Abbreviations: BDP, beclomethasone dipropionate; BMI, body mass index; BUD, budesonide; FSC, fluticasone propionate/salmeterol fixed-close combination; FP, fluticasone propionate; GPRD, General Practice Research Data base; SABD, short-acting bronchodilator; NA, not applicable.

Table 2 Crude and adjusted ORs and 95% CIs for FSC use and incident cataracts between 2003 and 2006

FSC	Crude OR	95% CI	Adjusted OR	95% CI
Ever use in the last year
No use in the last year	Reference	–	Reference	–
Use in the last year	1.19	(1.08–1.32)	1.1	(0.96–1.24)
Last use prior to index date (days)
No use in the last year	Reference	–	Reference	–
Last use prior 12 days	1.10	(0.92–1.33)	1.02	(0.83–1.27)
Last use prior 13–25 days	1.38	(1.16–1.64)	1.24	(1.01–1.51)
Last use prior 26–52 days	1.12	(0.94–1.34)	1.12	(0.91–1.38)
Last use prior 53–365 days	1.17	(0.98–1.4)	1.06	(0.87–1.30)
Duration of use (days)
No use in last year	Reference	–	Reference	–
1–90	1.15	(0.96–1.37)	1.06	(0.87–1.29)
91–180	1.14	(0.96–1.34)	1.05	(0.87–1.27)
181–270	1.28	(1.04–1.57)	1.18	(0.93–1.49)
≥271	1.25	(1.05–1.49)	1.20	(0.97–1.48)
Number of prescriptions
No prescriptions in last year	Reference	–	Reference	–
1–3	1.10	(0.92–1.31)	1.02	(0.84–1.24)
4–6	1.12	(0.95–1.33)	1.07	(0.88–1.30)
7–9	1.25	(1.02–1.53)	1.20	(0.95–1.52)
≥10	1.34	(1.13–1.59)	1.29	(1.05–1.59)

Notes: Population includes patients with COPD in the GPRD between 2003 and 2006. Controls matched to cases on gender, age within 2 years, general practice, and number of years in the cohort prior to the event of interest. Model adjusted for other inhaled corticosteroid use, asthma, long-acting beta agonists, short-acting bronchodilator, oral corticosteroid use, COPD hospitalizations, BMI, smoking status, statin use, depression, diabetes, rheumatoid arthritis, hypertension, oxygen use, nebulizer use, and count of antibiotic prescriptions.

Abbreviations: CI, confidence interval; FSC, fluticasone propionate/salmeterol fixed dose combination; GPRD, General Practice Research Database; OR, odds ratio.

Table 3 Crude and adjusted OR and 95% CI of the association between ICS use and incident cataracts between 2003 and 2006

ICS1	Crude OR	95% CI	Adjusted OR	95% CI
Ever use in the last year
No use	Reference	–	Reference	–
Ever use	1.32	(1.18–1.47)	1.10	(0.97, 1.24)
Last use prior to index date (days)
No use	Reference	–	Reference	–
18 days	1.19	(1.03–1.37)	1.19	(1.00, 1.41)
19–38 days	1.07	(0.91–1.25)	1.09	(0.90, 1.31)
39–100 days	1.06	(0.91–1.23)	1.08	(0.90, 1.28)
101–365 days	1.12	(0.97–1.3)	1.06	(0.90, 1.25)
Duration of use (days)
No use in last year	Reference	–	Reference	–
1–120	1.15	(0.99–1.33)	1.11	(0.94, 1.32)
121–230	0.99	(0.85–1.15)	0.99	(0.83, 1.18)
231–380	1.14	(0.98–1.32)	1.15	(0.97, 1.37)
≥381	1.17	(1.01–1.36)	1.22	(1.02, 1.46)
Number of prescriptions
No prescriptions in last year	Reference	–	Reference	–
1–3	1.06	(0.93–1.22)	1.07	(0.92, 1.25)
4–5	1.02	(0.87, 1.21)	1.02	(0.84, 1.23)
6–8	1.10	(0.95–1.28)	1.14	(0.95, 1.36)
≥9	1.27	(1.09–1.48)	1.33	(1.10, 1.60)

Notes: Population includes patients with COPD in the GPRD between 2003 and 2006. Controls matched to cases on gender, age within 2 years, general practice, and number of years in the cohort prior to the event of interest. Models adjusted for FSC, asthma, long-acting beta agonists, short-acting bronchodilators – containing product, oral corticosteroids, COPD hospitalizations, BMI, smoking status, statin use, depression, diabetes, rheumatoid arthritis, hypertension, oxygen use, nebulizer use, and count of antibiotic prescriptions.

1 ICS use excluding FSC.

Abbreviations: BMI, body mass index; CI, confidence interval; ICS, inhaled corticosteroids; GPRD, General Practice Research Database; OR, odds ratio.

Figure 1 Association between 1 year prior FSC or ICS prescriptions and odds of cataracts: average daily dose analysis.

Abreviations: FSC, fluticasone propionate/salmeterol fixed-close combination; ICS, inhaled corticosteroids.

Notes: Reference: low average daily dose.

Table 4 Crude and adjusted OR and 95% CI of the association between FSC use and incident glaucoma between 2003 and 2006

FSC	Crude OR	95% CI	Adjusted OR	95% CI
Ever use in the last year
No use	Reference	–	Reference	–
Use	0.84	(0.62–1.15)	0.68	(0.45–1.01)
Last use prior to index date (days)
No use	Reference	–	Reference	–
12 days	1.02	(0.61–1.71)	1.00	(0.53–1.89)
13–25 days	0.92	(0.52–1.62)	0.67	(0.34–1.30)
26–52 days	0.54	(0.3–0.97)	0.55	(0.28–1.09)
53–365 days	0.98	(0.58–1.65)	0.81	(0.44–1.52)
Duration of use (days)
No use	Reference	–	Reference	–
1–90	1.14	(0.66–1.97)	1.02	(0.54–1.90)
91–180	0.62	(0.36–1.08)	0.50	(0.26–0.96)
181–270	0.68	(0.36–1.28)	0.52	(0.25–1.08)
≥271	0.99	(0.61–1.59)	0.75	(0.42–1.34)
Number of prescriptions
No prescriptions in last year	Reference	–	Reference	–
1–3	1.14	(0.66–1.97)	1.01	(0.54–1.89)
4–6	0.63	(0.36–1.10)	0.49	(0.26–0.93)
7–9	0.70	(0.38–1.30)	0.50	(0.24–1.03)
≥10	0.96	(0.59–1.56)	0.72	(0.39–1.30)

Notes: Population includes patients with COPD in the GPRD between 2003 and 2006. Controls matched to cases on gender, age within 2 years, general practice, and number of years in the cohort prior to the event of interest. Model adjusted for other inhaled corticosteroids, asthma, long-acting beta agonists, short-acting bronchodilators, oral corticosteroids, BMI, smoking status, statin use, depression, diabetes, oxygen, nebulizer, and count of antibiotic prescriptions.

Abbreviations: BMI, body mass index; CI, confidence interval; FSC, fluticasone propionate/salmeterol fixed-dose combination; GPRD, General Practice Research Database OR, odds ratio.

Table 5 Crude and adjusted OR and 95% CI of the association between ICS use and incident glaucoma between 2003 and 2006

ICS	Crude OR	95% CI	Adjusted OR	95% CI
Ever use in the last year
No use	Reference	–	Reference	–
Use	0.98	(0.72–1.34)	0.94	(0.64–1.38)
Last use prior to index date (days)
No use	Reference	–	Reference	–
18 days	1.18	(0.77–1.81)	1.07	(0.62–1.82)
19–38 days	0.85	(0.53–1.35)	0.74	(0.41–1.34)
39–100 days	1.82	(1.19–2.76)	1.82	(1.08–3.05)
101–365 days	0.63	(0.38–1.04)	0.55	(0.31–0.99)
Duration of use (days)
No use	Reference	–	Reference	–
1–120	0.94	(0.6–1.47)	0.83	(0.49–1.43)
121–230	0.99	(0.61–1.6)	0.78	(0.43–1.4)
231–380	1.10	(0.71–1.68)	0.92	(0.53–1.58)
≥381	1.27	(0.83–1.94)	1.15	(0.68–1.95)
Number of prescriptions
None	Reference	–	Reference	–
1–3	0.91	(0.59–1.39)	0.85	(0.51–1.41)
4–5	1.29	(0.81–2.07)	1.17	(0.67–2.04)
6–8	1.12	(0.72–1.75)	0.86	(0.49–1.52)
≥9	1.07	(0.69–1.66)	0.86	(0.49–1.49)

Notes: Population includes patients with COPD in the GPRD between 2003 and 2006. Controls matched to cases on gender, age within 2 years, general practice, and number of years in the cohort prior to the event of interest. Models Adjusted for FSC, asthma, long-acting beta agonists, short-acting bronchodilators, oral corticosteroids, BMI, smoking status, statin use, depression, diabetes, oxygen use, nebulizer use, and count of antibiotic prescriptions.

Abbreviations: BMI, body mass index; CI, confidence interval; FSC, fluticasene propionate/salmeterol fixed-close combination; GPRD, General Practice Research Database OR, odds ratio.

Figure 2 Association between 1 year prior drug exposure and odds of glaucoma: average daily dose analysis.

Notes: Reference: low average daily dose.
Abbreviation: ICS, inhaled corticosteroids.