Journal List > J Rheum Dis > v.26(4) > 1137070

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

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.

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Figure 1.
Patient selection flow chart. FU2: second follow-up, FU3: third follow-up, FU4: fourth follow-up.
jrd-26-264f1.tif
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.
jrd-26-264f2.tif
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
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
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
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
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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