Background
Methods
Study population
Patient observation and evaluation
Study endpoints
Statistical analysis
Results
Enrolled patients
Baseline characteristics
Item | No. of enrolled patients (n = 5, 695)a
| No. of patients receiving remission maintenance (n = 4, 677)b
| ||||
---|---|---|---|---|---|---|
No. of patients | (%) | No. of patients | (%) | |||
Sex | Male | 3188 | (56.0) | 2610 | (55.8) | |
Female | 2505 | (44.0) | 2065 | (44.2) | ||
Unknown | 2 | (0.0) | 2 | (0.0) | ||
Age (years) | <20 | 8 | (0.1) | 4 | (0.1) | |
20–30 | 713 | (12.5) | 538 | (11.5) | ||
31–40 | 1327 | (23.3) | 1063 | (22.7) | ||
41–50 | 1371 | (24.1) | 1114 | (23.8) | ||
51–60 | 1010 | (17.7) | 869 | (18.6) | ||
61 - 70 | 826 | (14.5) | 713 | (15.2) | ||
≥71 | 435 | (7.6) | 373 | (8.0) | ||
Not indicated | 5 | (0.1) | 3 | (0.1) | ||
BMI | <18.5 | 609 | (10.7) | 485 | (10.4) | |
18.5–<25.0 | 4061 | (71.3) | 3354 | (71.7) | ||
≥25.0 | 975 | (17.1) | 801 | (17.1) | ||
Not indicated | 50 | (0.9) | 37 | (0.8) | ||
Disease stage | Disease stage | No. of patients | (%) | No. of patients | (%) | |
Active stage | Mild | 1303 | (22.9) | 574 | (12.3) | |
Moderate | 236 | (4.1) | 89 | (1.9) | ||
Not indicated | 1 | (0.0) | 1 | (0.0) | ||
Remission stage | 4155 | (73.0) | 4013 | (85.8) | ||
Extent of lesion | Total colitis type | 2378 | (41.8) | 1942 | (41.5) | |
Left-sided colitis type | 1951 | (34.3) | 1391 | (34.0) | ||
Proctitis type | 1243 | (21.8) | 1043 | (22.3) | ||
Other | 121 | (2.1) | 99 | (2.1) | ||
Not indicated | 2 | (0.0) | 2 | (0.0) | ||
Clinical course | First onset type | 953 | (16.7) | 838 | (17.9) | |
Relapse-remitting type | 3995 | (70.1) | 3427 | (73.3) | ||
Chronic continuous type | 745 | (13.1) | 410 | (8.8) | ||
Not indicated | 2 | (0.0) | 2 | (0.0) | ||
Drinking habit | No | 3250 | (57.1) | 2631 | (56.3) | |
≤1 day/week | 1201 | (21.1) | 992 | (21.2) | ||
2 - 5 days/week | 712 | (12.5) | 595 | (12.7) | ||
≥6 days/week | 513 | (9.0) | 443 | (9.5) | ||
Not indicated | 19 | (0.3) | 16 | (0.3) | ||
Smoking habit | No | 4207 | (73.9) | 3442 | (73.6) | |
Yes | 1473 | (25.9) | 1222 | (26.1) | ||
Not indicated | 15 | (0.3) | 13 | (0.3) | ||
Complications | Yes | 1166 | (20.5) | 966 | (20.7) | |
No | 4529 | (79.5) | 3711 | (79.3) | ||
Employment status | Student | 136 | (2.4) | 108 | (2.3) | |
Part-time worker | 645 | (11.3) | 534 | (11.4) | ||
Full-time worker | 3242 | (56.9) | 2632 | (56.3) | ||
Other | 1666 | (29.3) | 1401 | (30.0) | ||
Not indicated | 6 | (0.1) | 1 | (0.0) | ||
Use of oral 5-ASA agent | Pentasa® | 3023 | (53.1) | 2528 | (54.1) | |
Asacol® | 2202 | (38.7) | 1743 | (37.3) | ||
Salazopyrin® | 419 | (7.4) | 368 | (7.9) | ||
Other (generic) | 20 | (0.4) | 16 | (0.3) | ||
Concomitant use (oral products) | 28 | (0.5) | 22 | (0.5) | ||
Not indicated | 3 | (0.1) | 0 | (0.0) | ||
concomitant medication | Yes | 2669 | (46.9) | 2076 | (44.4) | |
No | 3026 | (53.1) | 2601 | (55.6) | ||
probiotics | 960 | (16.9) | 789 | (16.9) | ||
topical 5-ASA | 810 | (14.2) | 593 | (12.7) | ||
topical steroid | 259 | (4.5) | 170 | (3.6) | ||
systemic steroid | 401 | (7.0) | 275 | (5.9) | ||
immunomodulator | 870 | (15.3) | 699 | (14.9) | ||
anti-TNF | 169 | (3.0) | 129 | (2.8) | ||
tacrolims | 52 | (0.9) | 26 | (0.6) | ||
cyclosporine | 1 | (0.0) | 0 | (0.0) | ||
leukocyte apheresis | 37 | (0.6) | 21 | (0.4) | ||
pUCDAI and score of each category (Mean ± SD) | pUCDAI | 0.9 ± 1.5 (n = 5694) | 0.6 ± 1.2 (n = 4677) | |||
Stool frequency | 0.4 ± 0.7 (n = 5694) | 0.3 ± 0.6 (n = 4677) | ||||
Bloody stool | 0.2 ± 0.5 (n = 5695) | 0.1 ± 0.4 (n = 4677) | ||||
PGA | 0.3 ± 0.5 (n = 5695) | 0.2 ± 0.4 (n = 4677) | ||||
Duration of disease (mean ± SD) (months) | 108.2 ± 93.5 | 110.5 ± 95.0 | ||||
(n = 5670) | (n = 4658) | |||||
Duration of remission maintenance until enrollment | 31.4 ± 40.3 | 31.6 ± 40.5 | ||||
(mean ± SD) (months) | (n = 4107) | (n = 3958) | ||||
Drug adherence (mean ± SD) | 90.5 ± 14.2% (n = 5648) | 90.7 ± 13.7% (n = 4646) |
Results of the overall patients included in the observational study of remission maintenance
Remission maintenance rates by concomitant drugs, duration of disease
Remission maintenance rates by drugs, by dosage and frequency, by the extent of lesion, and by clinical course in real life
Remission maintenance rate by the presence or absence of dose reduction after remission had been induced in real life
Factors affecting relapse
Univariate analysis | Multivariate analysis#1
| |||||||
---|---|---|---|---|---|---|---|---|
No. of patients | Hazard ratio | Confidence interval of hazard ratio |
P-value for Wald test statistics | Hazard ratio | Confidence interval of hazard ratio |
P-value for Wald test statistics | ||
Age (years) | <20 | 4 | ||||||
20–30 | 538 | 0.778 | 0.109–5.563 |
p = 0.8028 | ||||
31–40 | 1063 | 0.611 | 0.086–4.358 |
p = 0.6233 | ||||
41–50 | 1114 | 0.545 | 0.076–3.887 |
p = 0.5450 | ||||
51–60 | 869 | 0.491 | 0.069–3.504 |
p = 0.4777 | ||||
61–70 | 713 | 0.414 | 0.058–2.966 |
p = 0.3802 | ||||
≥71 | 373 | 0.336 | 0.046–2.435 |
p = 0.2807 | ||||
Sex | Male | 2610 | ||||||
Female | 2065 | 1.165 | 1.024–1.326 |
p = 0.0201 | 1.126 | 0.988–1.282 |
p = 0.0744 | |
BMI | <18.5 | 485 | ||||||
18.5–<25.0 | 3354 | 0.883 | 0.718–1.087 |
p = 0.2411 | ||||
≥25.0 | 801 | 0.837 | 0.653–1.074 |
p = 0.1630 | ||||
Duration of disease (months) | <12 | 344 | ||||||
12–<60 | 1424 | 0.808 | 0.631–1.034 |
p = 0.0900 | ||||
60–<120 | 1238 | 0.738 | 0.573–0.950 |
p = 0.0186 | ||||
≥120 | 1652 | 0.692 | 0.541–0.885 |
p = 0.0034 | ||||
Classification by the extent of lesion | Total colitistype | 1942 | ||||||
Left-sided colitis type | 1591 | 1.204 | 1.042–1.393 |
p = 0.0121 | 1.159 | 1.001–1.341 |
p = 0.0487 | |
Proctitis type | 1043 | 0.910 | 0.762–1.086 |
p = 0.2937 | 0.957 | 0.800–1.144 |
p = 0.6271 | |
Other | 99 | 0.773 | 0.461–1.295 |
p = 0.3282 | 0.858 | 0.512–1.439 |
p = 0.5618 | |
Classification by linical course | First onset type | 838 | ||||||
Relapse-remitting type | 3427 | 1.608 | 1.325–1.952 |
p < 0.0001 | 1.456 | 1.198–1.770 |
p = 0.0002 | |
Chronic continuous type | 410 | 1.379 | 1.024–1.859 |
p = 0.0344 | 1.133 | 0.837–1.534 |
p = 0.4175 | |
Smoking habit | Yes | 1222 | ||||||
No | 3442 | 1.036 | 0.893–1.201 |
p = 0.6421 | ||||
Drinking habit | No | 2631 | ||||||
≤1 day/week | 992 | 1.060 | 0.900–1.247 |
p = 0.4865 | ||||
2–5 days/week | 595 | 1.058 | 0.867–1.289 |
p = 0.5797 | ||||
≥6 days/week | 443 | 1.050 | 0.842–1.309 |
p = 0.6670 | ||||
Complications | Yes | 965 | ||||||
No | 3712 | 1.094 | 0.930–1.286 |
p = 0.2788 | ||||
Employment status | Student | 108 | ||||||
Part-time worker | 534 | 0.751 | 0.497–1.135 |
p = 0.1740 | ||||
Full-time worker | 2632 | 0.705 | 0.482–1.031 |
p = 0.0714 | ||||
Other | 1401 | 0.626 | 0.424–0.925 |
p = 0.0186 | ||||
Concomitant use of infliximab/adalimumab | Yes | 129 | ||||||
No | 4548 | 1.319 | 0.847–2.054 |
p = 0.2205 | ||||
Concomitant use of tacrolimus | Yes | 26 | ||||||
No | 4651 | 0.722 | 0.300–1.738 |
p = 0.4674 | ||||
Concomitant use of immunomodulator | Yes | 602 | ||||||
No | 4075 | 0.874 | 0.727–1.051 |
p = 0.1517 | ||||
Concomitant use of probiotics | Yes | 789 | ||||||
No | 3888 | 0.919 | 0.777–1.086 |
p = 0.3208 | ||||
Concomitant use of 5-ASA enema/suppository | Yes | 594 | ||||||
No | 4083 | 0.757 | 0.631–0.909 |
p = 0.0028 | ||||
Drug adherence at enrollment | <80% | 705 | ||||||
≥80% | 3941 | 1.132 | 0.939–1.364 |
p = 0.1926 | ||||
Type of oral 5-ASA products at enrollment | Pentasa® Tablets | 2528 | ||||||
Asacol® Tablets | 1744 | 1.301 | 1.136–1.490 |
p = 0.0001 | ||||
Salazopyrin® Tablets | 368 | 1.273 | 1.007–1.608 |
p = 0.0435 | ||||
Other (generic) | 16 | 0.000 | 0.000 > 999.999 |
p = 0.9351 | ||||
Concomitant use (oral products) | 22 | 1.092 | 0.408–2.921 |
p = 0.8615 | ||||
Daily dose of oral 5-ASA products at enrollment (mg) | <1500 | 287 | ||||||
≥1500–<2500 | 1982 | 1.190 | 0.864–1.640 |
p = 0.2874 | ||||
≥2500 | 2408 | 1.780 | 1.301–2.436 |
p = 0.0003 | ||||
Duration of remission maintenance prior to enrollment#2 (months) | <3 | 1074 | ||||||
≥3–<12 | 1013 | 0.854 | 0.721–1.011 |
p = 0.0662 | 0.928 | 0.772–1.115 |
p = 0.4236 | |
≥12–<24 | 824 | 0.542 | 0.445–0.661 |
p < 0.0001 | 0.600 | 0.486–0.740 |
p < 0.0001 | |
≥24 | 1703 | 0.316 | 0.263–0.380 |
p < 0.0001 | 0.352 | 0.289–0.431 |
p < 0.0001 | |
Stool frequency score at enrollment | 0 | 3539 | ||||||
1 | 874 | 1.331 | 1.132–1.564 |
p = 0.0005 | 1.129 | 0.952–1.339 |
p = 0.1642 | |
2 | 195 | 1.788 | 1.351–2.366 |
p < 0.0001 | 1.334 | 0.986–1.806 |
p = 0.0618 | |
3 | 69 | 0.882 | 0.439–1.772 |
p = 0.7243 | 0.618 | 0.303–1.262 |
p = 0.1864 | |
Bloody stool score at enrollment | 0 | 4159 | ||||||
1 | 413 | 1.693 | 1.371–2.090 |
p < 0.0001 | 1.249 | 0.988–1.578 |
p = 0.0631 | |
2 | 98 | 2.712 | 1.845–3.987 |
p < 0.0001 | 1.721 | 1.126–2.628 |
p = 0.0120 | |
3 | 7 | 0.000 | 0.000–>999.999 |
p = 0.9476 | 0.000 | 0.000–>999.999 |
p = 0.9446 | |
PGA score at enrollment | 0 | 3830 | ||||||
1 | 770 | 1.564 | 1.324–1.847 |
p < 0.0001 | ||||
2 | 76 | 1.212 | 0.668–2.200 |
p = 0.5275 | ||||
3 | 1 | 0.001 | 0.000–>999.999 |
p = 0.9535 |