Introduction
Patients with moderately to severely active ulcerative colitis (UC) have debilitating symptoms that may incur substantial negative effects on health-related quality of life (HRQoL). According to the STRIDE-II consensus, restoration of HRQoL is a desirable long-term treatment goal for patients with active UC.1 In this post-hoc analysis, we evaluated the extent to which patients treated with upadacitinib (UPA) achieved normalisation of HRQoL after induction and maintenance treatment.
Aims & Methods
Data from the multicentre, double-blind, Phase 3 trials, U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026), were analysed. During induction, patients were randomised 1:2 to oral placebo (PBO) or UPA 45 mg once daily (QD) for 8 weeks. Patients achieving a clinical response to UPA per Adapted Mayo score at Week 8 were re-randomised 1:1:1 to PBO, UPA 15 mg, or UPA 30 mg QD for 52 weeks of maintenance. The proportion of patients achieving normalisation of each individual HRQoL outcome, per literature-base normative value thresholds, was assessed at Weeks 8 and 52: FACIT-Fatigue score; IBDQ score; WPAI-UC (overall work impairment, work time missed, impairment while working, activity impairment); SF-36 PCS; SF-36 MCS; EQ-5D-5L VAS; and EQ-5D-5L index. A stringent composite score including these outcomes was also calculated to determine the proportion of patients who achieved normalisation of all individual HRQoL-related scores. Point estimates were calculated for all outcomes and treatment differences between UPA and PBO were compared using the Cochran-Mantel-Haenszel test.
Results
During induction, 660 patients were randomised to UPA 45 mg and 328 patients to PBO. In patients receiving UPA 45 mg vs PBO, more patients achieved normalisation of each individual HRQoL outcome at Week 8 of induction (p<0.001; Table 1). Improvements were also observed at Week 52 of maintenance in patients receiving UPA 15 mg (n=148) and 30 mg (n=154), with more patients achieving normalisation of each HRQoL outcome with both doses of UPA vs PBO (p<=0.01). More patients achieved normalisation of composite HRQoL scores at Weeks 8 (UPA 45 mg: 18.9%; PBO: 5.5%) and 52 (UPA 30 mg: 24.0%; UPA 15 mg: 22.3%; PBO: 8.7%) with all doses of UPA compared to PBO (p<=0.001).
Table 1. Proportion of patients with UC achieving normalisation of HRQoL outcomes after treatment
HRQoL endpoints at
Weeks 8 and 52,
n (%) | Induction
(Week 8)
PBO
N=328 | Induction
(Week 8)
UPA 45 mg QD
N=660 | Between group diff. (UPA 45 mg vs PBO)
% [95% CI] | Maintenance (Week 52)
PBO
N=149 | Maintenance (Week 52)
UPA 15
mg QD
N=148 | Maintenance (Week 52)
UPA 30
mg QD
N=154 | Between group diff. (UPA 15 mg vs PBO)
% [95% CI] | Between group diff. (UPA 30 mg vs
PBO)
% [95% CI] |
| FACIT-F score ≥40.1 | 109 (33.2) | 357 (54.1) | 20.8 ***
[14.6, 27.1] | 53 (35.7) | 77 (52.0) | 86 (55.7) | 15.7 **
[5.1, 26.3] | 19.1 ***
[8.3, 29.8] |
| IBDQ score ≥170 | 85 (25.9) | 407 (61.6) | 35.6 ***
[29.6, 41.5] | 42 (28.5) | 91 (61.5) | 111 (72.3) | 32.2 ***
[22.1, 42.6] | 42.8 ***
[32.7, 52.8] |
WPAI-UC 0%
Overall work imp.a,b
Work time misseda,b
Imp. while workinga,b
Daily activity imp. |
24 (11.9)
92 (45.8)
27 (13.4)
37 (11.3)
|
112 (26.2)
261 (61.0)
126 (29.5)
199 (30.2)
|
13.7 ***
[7.7, 19.7]
14.7 ***
[6.5, 22.9]
15.3 ***
[9.1, 21.6]
18.8 ***
[14.0, 23.6] |
14 (13.9)
41 (40.6)
14 (13.9)
28 (18.8)
|
37 (33.9)
72 (66.1)
39 (35.8)
55 (37.2)
|
33 (32.7)
62 (61.4)
35 (34.7)
62 (40.3)
|
21.1 ***
[10.6, 31.6]
24.3 ***
[11.4, 37.2]
23.1 ***
[12.5, 33.7]
18.8 ***
[9.2, 28.5] |
19.0 ***
[7.9, 30.1]
19.7 **
[6.5, 33.0]
21.0 ***
[9.8, 32.2]
21.0 ***
[11.2, 30.8] |
| SF-36 PCS ≥50 | 106 (32.3) | 369 (55.9)
| 23.4 ***
[17.2, 29.7] | 44 (29.7)
| 89 (60.1)
| 102 (66.3)
| 29.5 **
[19.2, 39.8] | 35.4 ***
[25.1, 45.6] |
| SF-36 MCS ≥50 | 98 (29.9)
| 316 (48.0)
| 17.9 ***
[11.7, 24.1] | 38 (25.2)
| 70 (47.3)
| 82 (53.0)
| 22.1 ***
[12.0, 32.2] | 27.4 ***
[17.2, 37.7] |
| EQ-5D-5L VAS ≥80 | 68 (20.7)
| 298 (45.1)
| 24.3 ***
[18.6, 30.1] | 40 (26.9)
| 65 (43.9)
| 88 (57.1)
| 15.6 **
[5.1, 26.0] | 29.0 ***
[18.5, 39.6] |
| EQ-5D-5L Index ≥0.825 | 89 (27.1)
| 339 (51.4)
| 24.3 ***
[18.2, 30.4] | 49 (33.0)
| 79 (53.4)
| 90 (58.5)
| 18.7 ***
[8.3, 29.1] | 24.1 ***
[13.7, 34.6] |
| Composite HRQoL endpointc | 18 (5.5)
| 125 (18.9)
| 13.2 ***
[9.4, 17.1] | 13 (8.7)
| 33 (22.3)
| 37 (24.0)
| 13.8 ***
[6.0, 21.6] | 14.8 ***
[6.9, 22.7] |
**p≤0.01. ***p≤0.001. aInduction: PBO, N=201; UPA 45 mg, N=428. bMaintenance: PBO, N=101; UPA 15 mg, N=109; UPA 30 mg, N=101. cProportion of patients achieving FACIT-F score ≥40.1, IBDQ score ≥170, 0% for WPAI-UC Daily Activity Impairment, SF-36 PCS ≥50 and MCS ≥50, EQ-5D-5L VAS ≥80.0 and EQ-5D-5L Index ≥0.825; employment-related scores were excluded.
For induction data, the Cochran-Mantel-Haenszel test was used to calculate the 95% CI for differences between treatment groups and was adjusted for strata: baseline corticosteroid use (yes or no), baseline Adapted Mayo score (≤7 or >7) and bio-IR status (bio-IR or non–bio-IR).
For maintenance data, the Cochran-Mantel-Haenszel test was used to calculate the 95% CI for differences between treatment groups and was adjusted for strata: bio-IR status (bio-IR or non-bio-IR) at the baseline of the induction study, clinical remission status at Week 0 (yes or no), and corticosteroid use at Week 0 (yes or no).
Bio-IR, biologics inadequate response; CI, confidence interval; diff., difference; EQ-5D-5L, European Quality of Life 5 Dimensions 5 Levels; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HRQoL, health-related quality of life; IBDQ, Inflammatory Bowel Disease Questionnaire; imp., impairment; MCS, Mental Component Summary; PBO, placebo; PCS, Physical Component Summary; QD, once daily; SF-36, Short Form 36; UC, ulcerative colitis; UPA, upadacitinib; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment Questionnaire. |
Conclusion
UPA is more efficacious than PBO at achieving normalisation of patients’ HRQoL, at induction and through Week 52 of maintenance. These results suggest that UPA may help patients with moderately to severely active UC achieve the long-term treatment goal of normalisation of HRQoL.
References
- Turner D, et al. Gastroenterology. 2021;160:1570–83.
Disclosure
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.
Gareth Parkes received personal payments/honoraria/speaker fees and/or accepted travel grants or fellowships from AbbVie, Allergan, BMS, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts; and is a Director and Shareholder in Ampersand Health.
Corey Siegel has served as a consultant, advisor, speaker for CME activities, and/or received grant funding from AbbVie, BMS, Celltrion, Fresenius, Janssen, Lilly, Napo, Pfizer, Prometheus, Prometheus Labs, Roivant, and Takeda.
Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman; and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.
Edward V. Loftus Jr: served as a consultant for AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota, Iterative Scopes, Janssen, Morphic Therapeutics, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Sun Pharma, Takeda, and UCB; and received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, and UCB.
Remo Panaccione served as a consultant for Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, UCB; and received speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; and was an advisory board member for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.
Yuri Sanchez Gonzalez, Si Xuan, Valencia Remple, Justin Klaff, Cecile Holweg, and Dolly Sharmaare full-time employees of AbbVie and may hold AbbVie stock and/or stock options.
Funding statement: Financial support for the study was provided by AbbVie. AbbVie participated in interpretation of data, review, and approval of the abstract. All authors contributed to development of the abstract and maintained control over final content. No honoraria or payments were made for authorship. Medical writing services provided by Kay Hallam, MSc, of Fishawack Facilitate, Ltd, part of Avalere Health and funded by AbbVie.
