Effect of Drug Adherence on Treatment Outcome in Rheumatoid Arthritis

Yoon-Jeong Oh; Bumhee Park; Ki Won Moon

doi:10.4078/jrd.2019.26.4.264

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Oh, Park, and Moon: Effect of Drug Adherence on Treatment Outcome in Rheumatoid Arthritis

Original Article

J Rheum Dis 2019;26(4):264-272.

Published online: 31 October 2019

DOI: https://doi.org/10.4078/jrd.2019.26.4.264

Effect of Drug Adherence on Treatment Outcome in Rheumatoid Arthritis

Yoon-Jeong Oh¹, Bumhee Park^2,³, Ki Won Moon¹

¹Division of Rheumatology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea

²Department of Biomedical Informatics, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Korea

³Office of Biostatistics, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Korea

Corresponding to: Ki Won Moon http://orcid.org/0000-0002-4182-8328 Division of Rheumatology, Department of Internal Medicine, Kangwon National University School of Medicine, 1 Gangwondaehak-gil, Chuncheon 24341, Korea. E-mail: kiwonmoon@kangwon.ac.kr

Received 9 July 20191 August 2019 Accepted 11 August 2019

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

The present study aimed to evaluate the effect of drug adherence on treatment outcome in Korean patients with rheumatoid arthritis (RA).

Methods

A total of 2,694 RA patients who had complete data from annual follow-ups over three years in the Korean Observational Study Network for Arthritis were included in this study. Patients were divided into adherent and non-adherent groups according to data for drug adherence over three years. The European League against Rheumatism response and rate of disease flare were compared between two groups over three years. We also compared continuous variables representing treatment outcomes between the two groups.

Results

After propensity score matching using a ratio of 1:3, patients were allocated into non-adherent (n=522) and adherent (n=1,447) groups. The rate of non-response was higher in the non-ad-herent group over three years; however, there were no significant differences between continuous variables related to treatment outcome between the two groups. To evaluate the difference according to disease duration, patients were classified into early and late RA based on 48-month disease duration. In patients with early RA, the adherent group had lower patient's global health visual analog scale and lower disease activity 28 scores at three years compared with the nonadherence group. In patients with late RA, the non-adherent group had a higher rate of disease flare.

Conclusion

The adherent group tended to show lower disease activity, especially in early RA, whereas the nonadherence group was associated with non-response and higher risk of disease flare.

Keywords: Rheumatoid arthritis, Treatment adherence, Treatment outcome

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Figure 1.

Patient selection flow chart. FU2: second follow-up, FU3: third follow-up, FU4: fourth follow-up.

Figure 2.

The change of patient's (A) GH VAS and (B) DAS28-ESR between two groups in early RA patients (mean±standard deviation). GH VAS: global health visual analogue scale, DAS: disease activity score, ESR: erythrocyte sedimentation rate, FU2: second follow-up, FU3: third follow-up, FU4: fourth follow-up. *p-value <0.05.

Table 1.

Baseline characteristics between adherent and non-adherent groups before and after PSM using a ratio of 1:3

Variable	Before PSM			After PSM
Variable	Adherent (n=2,161)	Non-adherent (n=533)	p-value	Adherent (n=1,447)	Non-adherent (n=522)	p-value
Age (yr)	54.14±10.98	50.26±12.01	<0.01^*	51.57±10.85	50.49±11.94	0.07
Sex, female	1,852 (85.7)	473 (88.7)	0.06	1,265 (87.4)	462 (88.5)	0.54
BMI	22.77±3.22	22.56±3.07	0.19	22.62±3.21	22.56±3.06	0.71
Disease duration (mo)	84.59±64.97	74.91±57.41	<0.01^*	77.11±61.07	75.46±57.54	0.59
ACR criteria number
<4	101 (4.7)	22 (4.1)	0.36	63 (4.4)	21 (4.0)	0.74
≥4	2,060 (95.3)	511 (95.9)		1,384 (95.6)	501 (96.0)
Current smoker	146 (6.8)	38 (7.1)	0.26	97 (6.7)	37 (7.1)	0.96
Side effects	715 (33.1)	229 (43.0)	<0.01^*	556 (38.4)	220 (42.1)	0.18
Income (USD/mo)
<2,000	1,430 (66.5)	297 (55.8)	<0.01^*	876 (60.5)	296 (56.7)	0.09
2,000∼4,990	574 (26.7)	184 (34.6)		466 (32.2)	180 (34.5)
≥5,000	145 (6.7)	51 (9.6)		105 (7.3)	46 (8.8)
Education
Middle school or less	950 (44.2)	1,201 (55.8)	<0.01^*	541 (37.4)	173 (33.1)	0.09
High school or more	174 (32.6)	359 (67.4)		906 (62.6)	349 (66.9)
Rheumatoid factor	1,493 (69.1)	386 (72.4)	0.14	1,042 (72.0)	375 (71.8)	0.96
ACPA	1,486 (68.8)	352 (66.0)	0.23	976 (67.4)	344 (65.9)	0.52
Medication
MTX	1,867 (86.4)	460 (86.3)	0.94	1,250 (86.4)	450 (86.2)	0.94
NSAID	1,795 (83.1)	444 (83.3)	0.95	1,203 (83.1)	434 (83.1)	1.00
Steroid	1,805 (83.5)	444 (83.3)	0.90	1,191 (82.3)	433 (83.0)	0.79
Biologics	170 (7.9)	26 (4.9)	<0.05^*	77 (5.3)	26 (5.0)	0.82
Physician's VAS score	24.42±18.17	22.05±16.39	<0.01^*	22.55±17.09	22.11±16.45	0.61
Patient's GH VAS score	37.86±25.64	37.65±25.23	0.86	37.06±25.61	37.44±25.23	0.77
DAS28-ESR	3.67±1.30	3.57±1.30	<0.05^*	3.58±1.28	3.57±1.30	0.85
EQ5D	0.69±0.23	0.72±0.23	<0.05^*	0.71±0.22	0.72±0.23	0.67
HAQ	0.66±0.62	0.56±0.58	<0.01^*	0.58±0.56	0.56±0.58	0.53
ESR	29.93±24.34	27.40±22.10	<0.05^*	28.06±23.03	27.55±22.18	0.67
CRP	0.82±1.39	0.71±1.50	0.12	0.74±1.18	0.72±1.52	0.68

Values are presented as mean±standard deviation or number (%). PSM: propensity score matching, BMI: body mass index, ACR: American college of rheumatology, USD: United States dollar, ACPA: anti-citrullinated peptide antibody, MTX: methotrexate, NSAID: non-steroidal anti-inflammatory drug, VAS: visual analog scale, GH: global health, DAS: disease activity score, ESR: erythrocyte sedimentation rate, EQ5D: EuroQol-5D, HAQ: health assessment questionnaire, CRP: C-reactive protein.

^* Asterisk values indicate statistical significance with p<0.05.

Table 2.

EULAR response and disease flare between the adherent and non-adherent groups over three years

Variable	Total population			Early RA			Late RA
Variable	Adherent (n=1,447)	Non-adherent (n=522)	p-value	Adherent (n=483)	Non-adherent (n=186)	p-value	Adherent (n=894)	Non-adherent (n=332)	p-value
EULAR response
Good	302 (20.9)	93 (17.8)	0.14	135 (28.0)	38 (20.4)	<0.05^*	160 (17.9)	53 (16.0)	0.45
Moderate	322 (22.3)	105 (20.1)	0.32	103 (21.3)	42 (22.6)	0.75	200 (22.4)	65 (19.6)	0.31
None	823 (56.9)	324 (62.1)	<0.05^*	245 (50.7)	106 (57.0)	0.17	534 (59.7)	214 (64.5)	0.15
Disease flare
FU2 flare	253 (17.5)	108 (20.7)	0.11	70 (14.5)	32 (17.2)	0.40	160 (17.9)	74 (22.3)	0.09
FU3 flare	265 (18.3)	102 (19.5)	0.56	79 (16.4)	32 (17.2)	0.82	158 (17.7)	69 (20.8)	0.22
FU4 flare	245 (16.9)	107 (20.5)	0.07	65 (13.5)	32 (17.2)	0.22	161 (18.0)	74 (22.3)	0.10
Any flare	511 (35.3)	203 (38.9)	0.15	147 (30.4)	59 (31.7)	0.78	317 (25.5)	142 (42.8)	<0.05^*

Values are presented as number (%). Early and advanced RA was classified according to disease duration of 48 months. Flares were defined as any flare occurring during the follow-up period. EULAR: European league against rheumatism, RA: rheumatoid arthritis, FU2: second follow-up, FU3: third follow-up, FU4: fourth follow-up.

^* Asterisk values indicate statistical significance with p<0.05.

Table 3.

Comparisons of continuous variables related to treatment outcome between the adherent and non-adherent groups over 3 years

Variable	Total population			Early RA			Late RA
Variable	Adherent (n=1,447)	Non-adherent (n=522)	p-value	Adherent (n=483)	Non-adherent (n=186)	p-value	Adherent (n=894)	Non-adherent (n=332)	p-value
FU2
Physician's	16.60±15.04	16.27±14.32	0.67	15.26±14.28	16.56±15.28	0.30	17.34±15.40	16.15±13.83	0.19
VAS score
Patient's GH	35.07±24.30	36.85±24.13	0.15	31.05±23.04	35.80±25.75	<0.05^*	37.42±24.42	37.30±23.24	0.94
VAS score
DAS28-ESR	3.25±1.31	3.31±1.26	0.41	2.97±1.27	3.04±1.21	0.52	3.44±1.29	3.46±1.26	0.77
EQ5D	0.73±0.22	0.72±0.22	0.18	0.78±0.19	0.76±0.19	0.16	0.71±0.21	0.69±0.23	0.41
HAQ	0.52±0.58	0.51±0.57	0.52	0.36±0.46	0.37±0.50	0.82	0.62±0.60	0.58±0.59	0.26
ESR	25.77±21.57	26.50±23.02	0.51	23.55±21.02	22.73±19.46	0.64	27.05±21.46	28.68±24.49	0.26
CRP	0.72±2.95	0.59±1.00	0.33	0.94±5.11	0.55±0.82	0.30	0.64±1.02	0.62±1.10	0.83
FU3
Physician's	15.88±13.51	15.62±12.81	0.70	15.54±13.03	15.19±12.76	0.75	16.27±14.02	15.62±12.17	0.45
VAS score
Patient's GH	34.35±23.43	35.71±13.17	0.25	30.30±22.98	32.80±23.03	0.21	36.57±22.79	36.94±23.11	0.80
VAS score
DAS28-ESR	3.19±1.26	3.21±1.20	0.79	2.93±1.20	2.96±1.17	0.75	3.34±1.25	3.33±1.19	0.87
EQ5D	0.73±0.22	0.75±0.20	0.07	0.77±0.21	0.80±0.20	0.10	0.71±0.21	0.72±0.20	0.30
HAQ	0.53±0.57	0.47±0.54	0.06	0.40±0.45	0.33±0.46	0.51	0.62±0.59	0.55±0.57	0.08
ESR	26.25±20.78	26.77±22.56	0.63	24.27±21.15	24.05±20.62	0.90	27.80±20.49	28.28±23.39	0.73
CRP	0.58±0.96	0.61±1.31	0.67	0.56±0.99	0.67±1.89	0.48	0.74±3.60	0.58±0.57	0.42
FU4
Physician's	16.28±13.65	15.77±13.72	0.47	14.68±13.51	14.82±13.78	0.91	16.81±13.87	16.49±13.68	0.72
VAS score
Patient's GH	35.06±23.93	33.32±25.79	0.13	29.40±22.21	35.22±24.03	<0.01^*	38.32±23.83	38.18±24.26	0.92
VAS score
DAS28-ESR	3.17±1.17	3.26±1.12	0.12	2.87±1.12	3.08±1.11	<0.05^*	3.36±1.17	3.37±1.11	0.87
EQ5D	0.72±0.23	0.73±0.21	0.31	0.77±0.20	0.77±0.21	0.61	0.69±0.23	0.71±0.21	0.05
HAQ	0.57±0.61	0.53±0.59	0.15	0.38±0.47	0.38±0.48	0.87	0.68±0.64	0.61±0.63	0.11
ESR	26.26±20.33	26.41±18.90	0.88	23.54±19.04	24.85±20.16	0.43	28.33±21.46	27.36±18.30	0.43
CRP	0.78±2.92	0.86±4.69	0.62	0.62±1.17	1.25±7.74	0.27	0.72±1.37	0.67±0.99	0.54

Values are presented as mean±standard deviation. Early and advanced RA was classified according to disease duration of 48 months. RA: rheumatoid arthritis, VAS: visual analog scale, GH: global health, DAS: disease activity score, ESR: erythrocyte sedimentation rate, EQ5D: EuroQol-5D, HAQ: health assessment questionnaire, CRP: C-reactive protein, FU2: second follow-up, FU3: third follow-up, FU4: fourth follow-up.

^* Asterisk values indicate statistical significance with p<0.05.

Table 4.

Baseline characteristics between the adherent and non-adherent groups after propensity score matching using a ratio of 1:3 in early and late RA, according to disease duration of 48 months

Variable	Early RA			Late RA
Variable	Adherent (n=483)	Non-adherent (n=186)	p-value	Adherent (n=894)	Non-adherent (n=332)	p-value
Age (yr)	49.75±11.17	48.34±12.28	0.16	52.50±10.45	51.96±11.34	0.45
Sex, female	393 (81.4)	153 (82.3)	0.83	818 (91.5)	305 (91.9)	0.91
BMI	22.80±3.12	22.67±3.10	0.63	22.52±3.25	22.55±3.03	0.88
Disease duration (mo)	21.86±14.32	23.27±14.67	0.26	106.60±53.60	105.24±51.43	0.69
ACR criteria number
<4	21 (4.3)	9 (4.8)	0.43	28 (3.1)	12 (3.6)	0.93
≥4	462 (95.7)	177 (95.2)		866 (96.9)	320 (96.4)
Current smoker	50 (10.4)	19 (10.2)	0.73	42 (4.7)	16 (4.8)	0.96
Side effect	181 (37.5)	77 (41.4)	0.37	354 (39.6)	142 (42.8)	0.43
Income (USD/mo)
<2,000	285 (59.0)	102 (54.8)	0.36	554 (62.0)	194 (58.4)	0.27
2000∼4990	163 (33.7)	71 (38.2)		279 (31.2)	111 (33.4)
≥5,000	35 (7.2)	13 (7.0)		61 (6.8)	27 (8.1)
Education
Middle school or less	163 (33.7)	320 (66.3)	0.22	348 (38.9)	546 (61.1)	0.26
High school or more	53 (28.5)	133 (71.5)		119 (35.8)	213 (64.2)
Rheumatoid factor	346 (71.6)	133 (71.5)	1.00	642 (71.8)	241 (72.6)	0.83
ACPA	389 (80.5)	148 (79.6)	0.83	537 (60.1)	195 (58.7)	0.69
Medication
MTX	421 (87.2)	157 (84.4)	0.38	776 (86.8)	291 (87.7)	0.77
NSAID	392 (81.2)	153 (82.3)	0.82	749 (83.8)	279 (84.0)	1.00
Steroid	405 (83.9)	156 (83.9)	1.00	741 (82.9)	274 (82.5)	0.87
Biologics	24 (5.0)	8 (4.3)	0.84	55 (6.2)	18 (5.4)	0.69
Physician's VAS	23.02±17.75	23.14±16.51	0.94	22.47±16.84	21.76±16.41	0.51
Patient's GH VAS	35.17±25.63	35.33±25.42	0.94	38.11±25.55	38.90±25.08	0.63
DAS28-ESR	3.49±1.34	3.49±1.34	0.97	3.70±1.27	3.62±1.27	0.29
EQ5D	0.74±0.22	0.75±0.23	0.73	0.70±0.21	0.70±0.24	0.79
HAQ	0.49±0.52	0.46±0.55	0.51	0.65±0.59	0.62±0.59	0.49
ESR	29.18±26.30	28.18±22.94	0.65	29.64±21.87	27.17±21.85	0.33
CRP	1.04±1.86	0.99±2.30	0.82	0.62±0.79	0.55±0.74	0.18

Values are presented as mean±standard deviation or number (%). RA: rheumatoid arthritis, BMI: body mass index, ACR: American college of rheumatology, USD: United States dollar, ACPA: anti-citrullinated peptide antibody, MTX: methotrexate, NSAID: non-steroidal anti-inflammatory drug, VAS: visual analog scale, GH: global health, DAS: disease activity score, ESR: erythrocyte sedimentation rate, EQ5D: EuroQol-5D, HAQ: health assessment questionnaire, CRP: C-reactive protein.

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