Impact of adherence to biological agents on health care resource utilization for patients over the age of 65 years with rheumatoid arthritis

Figures & data

Table 1 Biologic treatments of interest

Brand name	Generic name	DIN	Dose and dose frequency
Anti-TNF agents
Humira	Adalimumab	02258595	40 mg every 2 weeks
		09857294
		09857326
		09857327
Enbrel^®	Etanercept	02242903	25 mg twice weekly or 50 mg once weekly
		02274728
		09857322
		09857394
Remicade^®	Infliximab	02244016	3 mg/kg/dose at 0 weeks, 2 weeks and 6 weeks followed by maintenance therapy of
		09852956	3 mg/kg/dose every 8 weeks up to a maximum of six maintenance doses per year
Cimzia^®	Certolizumab	02331675	400 mg at 0 weeks, 2 weeks and 4 weeks followed by maintenance therapy of 200 mg every 2 weeks. For maintenance dosing, 400 mg every 4 weeks may be considered
Simponi^®	Golimumab	02324776	50 mg once a month
		02324784
Other mechanism of action
Kineret^®	Anakinra	02245913	100 mg per day
Actemra^®	Tocilizumab	02350092 02350106 02350114	4 mg/kg/dose once every 4 weeks followed by an increase to 8 mg/kg/dose based on clinical response. For individuals whose body weight is ⩾100 kg, doses exceeding 800 mg per infusion are not recommended
Orencia^®	Abatacept	02282097	IV: Year 1: 750 mg at weeks 0, 2 and 4 then every 4 weeks
		02402475	SC: 125 mg weekly
Rituxan^®	Rituximab	02241927 09857407	One course of treatment is 1,000 mg followed 2 weeks later by the second 1,000 mg dose. Two courses will be approved each year (courses should be at least 6 months)

Abbreviations: DIN, drug identification number; TNF, tumor necrosis factor; IV, intravenously; SC, subcutaneously.

Table 2 Baseline characteristics

Characteristics	Overall	Adherent (MPR ≥0.8)	Non-adherent (MPR ⩽0.8)	P-value
	N=4,667	n=2,196	n=2,471
Index year, n (%)				⩽0.001
2003	456 (9.8)	149 (6.8)	307 (12.4)
2004	237 (5.1)	78 (3.6)	159 (6.4)
2005	283 (6.1)	97 (4.4)	186 (7.5)
2006	279 (6)	97 (4.4)	182 (7.4)
2007	327 (7)	135 (6.1)	192 (7.8)
2008	406 (8.7)	166 (7.6)	240 (9.7)
2009	451 (9.7)	200 (9.1)	251 (10.2)
2010	349 (7.5)	157 (7.1)	192 (7.8)
2011	524 (11.2)	291 (13.3)	233 (9.4)
2012	658 (14.1)	385 (17.5)	273 (11)
Long-term care resident, n (%)	27 (0.6)	13 (0.7)	14 (0.5)	0.454
Demographics
Age, mean (SD)	69.94 (5.46)	70.60 (5.69)	69.47 (5.24)	⩽0.001
Female, n (%)	3,500 (75.0)	1,453 (75.8)	2,047 (74.5)	0.301
Income quintile, n (%)				0.211
Missing	16 (0.3)	8 (0.4)	8 (0.3)
1 – lowest	744 (15.9)	323 (16.8)	421 (15.3)
2	892 (19.1)	385 (20.1)	507 (18.4)
3	946 (20.3)	386 (20.1)	560 (20.4)
4	1,055 (22.6)	405 (21.1)	650 (23.6)
5 – highest	1,013 (21.7)	410 (21.4)	603 (21.9)
Geographics
Rural, n (%)	706 (15.1)	354 (16.1)	352 (14.2)	0.074
Health resource utilization
RUB, n (%)				⩽0.001
0–2	11 (0.2)	6–10*	1–5*
3	2,296 (49.2)	864 (45.1)	1,432 (52.1)
4	1,580 (33.9)	687 (35.8)	893 (32.5)
5	779 (16.7)	356–360*	419–423*
MD visits
GP/FP
Any visit, n (%)	4,562 (97.8)	1,873 (97.7)	2,689 (97.8)	0.798
Mean (SD)	12.7 (12.57)	13.5 (12.57)	12.1 (12.54)	⩽0.001
Median (IQR)	9 (5–16)	10 (6–17)	9 (5–15)	⩽0.001
Rheumatologist
Any visit, n (%)	2,682 (57.5)	1,045 (54.5)	1,637 (59.5)	⩽0.001
Mean (SD)	3.7 (4.89)	3.5 (4.89)	3.9 (4.89)	0.017
Median (IQR)	2 (0–6)	1 (0–6)	2 (0–6)	0.017
Cardiologist
Any visit, n (%)	1,144 (24.5)	512 (26.7)	632 (23)	0.004
Mean (SD)	0.6 (1.99)	0.7 (2.44)	0.5 (1.6)	0.001
Median (IQR)	0 (0–0)	0 (0–1)	0 (0–0)	0.001
Other
Any visit, n (%)	4,589 (98.3)	1,891 (98.6)	2,698 (98.1)	0.188
Mean (SD)	12.8 (10.25)	13.5 (11.52)	12.3 (9.22)	⩽0.001
Median (IQR)	11 (6–17)	11 (6–18)	10 (6–17)	⩽0.001
ED visits
Any visit, n (%)	1,706 (36.6)	777 (40.5)	929 (33.8)	⩽0.001
Mean (SD)	0.7 (1.42)	0.9 (1.6)	0.7 (1.27)	⩽0.001
Median (IQR)	0 (0–1)	0 (0–1)	0 (0–1)	⩽0.001
Same-day surgeries
Any visit, n (%)	1,180 (25.3)	502 (26.2)	678 (24.7)	0.239
Mean (SD)	0.4 (0.76)	0.4 (0.77)	0.4 (0.75)	0.521
Median (IQR)	0 (0–1)	0 (0–1)	0 (0–0)	0.521
Hospitalizations
Any visit, n (%)	845 (18.1)	410 (21.4)	435 (15.8)	⩽0.001
Mean (SD)	0.2 (0.59)	0.3 (0.64)	0.2 (0.55)	⩽0.001
Median (IQR)	0 (0–0)	0 (0–0)	0 (0–0)	⩽0.001
LOS
Mean (SD)	9.1 (12.18)	9.1 (11.6)	9.1 (12.72)	0.96
Median (IQR)	5 (3–10)	6 (3–10)	5 (2–10)	0.96
Home care
Any service, n (%)	338 (7.2)	170 (8.9)	168 (6.1)	⩽0.001
Mean (SD)	7.7 (47.32)	10.3 (57.08)	5.8 (39.01)	0.001
Median (IQR)	0 (0–0)	0 (0–0)	0 (0–0)	0.001
Rehabilitation
Any rehabilitation, n (%)	481 (10.3)	206 (10.7)	275 (10)	0.412
Mean (SD)	0.1 (0.47)	0.1 (0.49)	0.1 (0.45)	0.351
Median (IQR)	0 (0–0)	0 (0–0)	0 (0–0)	0.351

Note:

* Suppressed for privacy.

Abbreviations: MPR, medication possession ratio; SD, standard deviation; RUB, resource utilization band; MD, medical doctor; GP, general practitioner; FP, family practitioner; IQR, interquartile range; ED, emergency department; LOS, length of stay.

Table 3 Logistic regression results predicting overall adherence to biologic drugs among patients with RA in Ontario

	Odds ratio (95% CI)
Patient characteristics
Age	0.97 (0.96–0.98)
Female	0.93 (0.81–1.07)
Income quintile (REF =1 – lowest)
2	1.03 (0.84–1.26)
3	1.12 (0.91–1.36)
4	1.22 (1.0–1.49)
5 – highest	1.14 (0.94–1.39)
Rural	1.18 (0.98–1.43)
Long-term care resident	1.23 (0.55–2.75)
Drug use prior to index date
NSAIDs/COXIBs	0.83 (0.73–0.94)
Corticosteroids
Oral prednisone	0.89 (0.78–1.01)
Intra-articular steroid injections	0.96 (0.84–1.10)
Other	0.48 (0.19–1.25)
DMARDs
MTX	1.19 (1.05–1.36)
Others	1.16 (1.01–1.33)
Anti-hypertensives	0.84 (0.79–0.96)
Health services use prior to index date
RUB (REF =0–2)
3	2.81 (0.8–9.85)
4	2.42 (0.69–8.53)
5	2.63 (0.74–9.36)
Number of MD visits
GP/FP	1.00 (0.99–1.00)
Rheumatologist	1.02 (1.00–1.03)
Cardiologist	0.97 (0.94–1.01)
Others	1.00 (0.99–1.00)
Number of ED visits	0.96 (0.91–1.01)
Number of same-day surgeries	1.04 (0.96–1.13)
Number of hospitalizations	0.95 (0.83–1.08)
Number of home care services	1.00 (1.00–1.00)
Number of rehabilitation services	1.05 (0.91–1.20)

Note: Bold represent statistically significant values.

Abbreviations: RA, rheumatoid arthritis; REF, reference; NSAIDs, non-steroidal anti-inflammatory drugs; COXIBs, COX-2 inhibitors; DMARDs, disease-modifying anti-rheumatic drugs; MTX, methotrexate; RUB, resource utilization band; MD, medical doctor; GP, general practitioner; FP, family practitioner; ED, emergency department.

Table 4 Medication use, among those aged 66 years and older, before and after the index date

Drug group, n (%)	Overall	Adherent (MPR ≥0.8)	Non-Adherent (MPR ⩽0.8)	P-value
	N=3,181	n=1,418	n=1,763
Prior to index date
NSAIDs/COXIBs	1,607 (50.5)	724 (51.1)	883 (50.1)	0.585
Corticosteroids
Any use	2,136 (67.1)	960 (67.7)	1,176 (66.7)	0.552
Oral prednisone	1,719 (54)	796 (56.1)	923 (52.4)	0.033
Intra-articular steroid injections	1,433 (45)	623 (43.9)	810 (45.9)	0.258
Others	16 (0.5)	11–15	1–5	0.051
DMARDs
Any use	2,869 (90.2)	1,258 (88.7)	1,611 (91.4)	0.012
MTX	2,024 (63.6)	846 (59.7)	1,178 (66.8)	⩽0.001
Others	2,442 (76.8)	1,042 (73.5)	1,400 (79.4)	⩽0.001
Anti-hypertensives	2,017 (63.4)	933 (65.8)	1,084 (61.5)	0.012
Index date to the end of follow-up
NSAIDs/COXIBs	1,773 (55.7)	829 (58.5)	944 (53.5)	0.006
Corticosteroids
Any use	2,394 (75.3)	1,120 (79)	1,274 (72.3)	⩽0.001
Oral prednisone	1,947 (61.2)	955 (67.3)	992 (56.3)	⩽0.001
Intra-articular steroid injections	1,690 (53.1)	785 (55.4)	905 (51.3)	0.024
Others	109 (3.4)	65 (4.6)	44 (2.5)	0.001
DMARDs
Any use	2,656 (83.5)	1,174 (82.8)	1,482 (84.1)	0.338
MTX	1,913 (60.1)	832 (58.7)	1,081 (61.3)	0.13
Others	1,693 (53.2)	797 (56.2)	896 (50.8)	0.002
Anti-hypertensives	2,463 (77.4)	1,145 (80.7)	1,318 (74.8)	⩽0.001

Note: Bold represent statistically significant values.

Abbreviations: MPR, medication possession ratio; NSAIDs, non-steroidal anti-inflammatory drugs; COXIBs, COX-2 inhibitors; DMARDs, disease-modifying anti-rheumatic drugs; MTX, methotrexate.

Table 5 Resource use for the matched* cohort

Resource	Resource use			P-value
	Total	Adherent (MPR ≥0.8)	Non-adherent (MPR <<0.8)
	N=3<686	n=1<843	n=1,843
Follow-up time (days)
Mean (SD)	1<943 (1<112)	1<919 (1<085)	1,967 (1,138)	0.187
Median (IQR)	1<831 (1<003–2<736)	1<828 (974–2<673)	1,836 (1,018–2,786)	0.187
GP/FP
Any visit, n (%)	3<670 (99.6)	1<834 (99.5)	1,836 (99.6)	0.616
Rate per 100 follow-up days
Mean (SD)	4.34 (3.80315)	4.7 (4.06444)	3.97 (3.48451)	⩽0.001
Median (IQR)	3.25 (1.9753–5.3486)	3.58 (2.1277–5.8315)	2.93 (1.8328–4.798)	⩽0.001
Rheumatologist
Any visit, n (%)	3<161 (85.8)	1<562 (84.8)	1,599 (86.8)	0.081
Rate per 100 follow-up days
Mean (SD)	1.37 (1.44)	1.25 (1.38)	1.49 (1.49)	⩽0.001
Median (IQR)	0.96 (0.34–1.93)	0.84 (0.26–1.75)	1.09 (0.46–2.08)	⩽0.001
Cardiologist
Any visit, n (%)	2<588 (70.2)	1<352 (73.4)	1,236 (67.1)	⩽0.001
Rate per 100 follow-up days
Mean (SD)	0.34 (0.68)	0.39 (0.75)	0.29 (0.59)	⩽0.001
Median (IQR)	0.12 (0–0.37)	0.15 (0–0.44)	0.097 (0–0.31)	⩽0.001
Other
Any visit, n (%)	3<682 (99.9)	1<841 (99.9)	1,841 (99.9)	1
Rate per 100 follow-up days
Mean (SD)	4.59 (3.88)	5.00 (4.31)	4.2 (3.35)	⩽0.001
Median (IQR)	3.7 (2.27–5.6)	3.9 (2.38–6.17)	3.47 (2.13–5.26)	⩽0.001
ED visits
Any visit, n (%)	3<059 (83)	1<601 (86.9)	1,458 (79.1)	⩽0.001
Rate per 365 follow-up days
Mean (SD)	1.71 (1.75)	1.35 (2.00)	1.00 (1.50)	⩽0.001
Median (IQR)	0.69 (0.23–1.51)	0.84 (0.33–1.64)	0.55 (0.16–1.20)	⩽0.001
Same-day surgeries
Any visit, n (%)	2<386 (64.7)	1<214 (65.9)	1,172 (63.6)	0.148
Rate per 365 follow-up days
Mean (SD)	0.37 (0.58)	0.39 (0.58)	0.35 (0.57)	0.037
Median (IQR)	0.23 (0–0.52)	0.25 (0–0.54)	0.22 (0–0.50)	0.037
Hospitalizations
Any visit, n (%)	2<390 (64.8)	1<293 (70.2)	1,097 (59.5)	⩽0.001
Rate per 365 follow-up days
Mean (SD)	0.48 (0.78)	0.58 (0.80)	0.39 (0.75)	⩽0.001
Median (IQR)	0.24 (0–0.62)	0.33 (0–0.78)	0.18 (0–0.48)	⩽0.001
Length of stay (in days)
Mean (SD)	29.93 (40.5)	37.69 (48.62)	20.79 (25.18)	⩽0.001
Median (IQR)	15 (6–38)	19 (6–51)	11 (5–28)	⩽0.001
Home care
Any service, n (%)	1<220 (33.1)	723 (39.2)	497 (27)	⩽0.001
Rate per 365 follow-up days
Mean (SD)	23.86 (75.92)	28.10 (76.76)	19.60 (75.19)	⩽0.001
Median (IQR)	0 (0–1.2195)	0 (0–3.2164)	0 (0–0.1628)	⩽0.001
Rehabilitation
Any rehabilitation, n (%)	533 (14.5)	327 (17.7)	206 (11.2)	⩽0.001
Rate per 365 follow-up days
Mean (SD)	0.04 (0.135)	0.05 (0.16)	0.02 (0.01)	⩽0.001
Median (IQR)	0 (0–0)	0 (0–0)	0 (0–0)	⩽0.001

Notes:

* Adherent patients were matched to non-adherent patients on a PS calculated using age, sex, income quintile, LHIN of residence, rurality, RUB, index year of first biologic script and health services use prior to index date (visits to GP/FP, rheumatologists, cardiologists and other MDs, ED visits, hospitalizations, same-day surgeries, home care services and rehabilitation episodes).

Abbreviations: MPR, medication possession ratio; SD, standard deviation; IQR, interquartile range; GP, general practitioner; FP, family practitioner; ED, emergency department; PS, propensity score; RUB, resource utilization band; MD, medical doctor; LHIN, Local Health Integration Network.

Table 6 Relative rates for resource use for the matched* cohort, using negative binomial distribution

Resource use	Adherence over entire follow-up period
	Relative rate	Lower CL	Upper CL
MD visits
GP/FP	0.88	0.83	0.93
Rheumatologist	1.06	1.00	1.12
Cardiologist	0.78	0.69	0.88
Others	0.82	0.78	0.86
ED visits	0.75	0.69	0.82
Same-day surgeries	0.91	0.84	0.98
Hospitalizations	0.68	0.63	0.74
Home care	0.72	0.55	0.93
Rehabilitation	0.60	0.49	0.74

Notes:

* Adherent patients were matched to non-adherent patients on a PS calculated using age, sex, income quintile, LHIN of residence, rurality, RUB, index year of first biologic script and health services use prior to index date (visits to GP/FP, rheumatologists, cardiologists, and other MDs, ED visits, hospitalizations, same-day surgeries, home care services and rehabilitation episodes).

Abbreviations: CL, confidence limit; MD, medical doctor; GP, general practitioner; FP, family practitioner; ED, emergency department; PS, propensity score; RUB, resource utilization band; LHIN, Local Health Integration Network.