Introduction
Ulcerative colitis (UC) is associated with symptoms that may considerably impair patients’ health-related quality of life (HRQoL). Long-term treatment goals established in STRIDE-II include the recuperation of HRQoL in patients with active UC.1 This post-hoc analysis evaluated the impact of Risankizumab (RZB) as induction and maintenance therapy on normalisation of HRQoL in patients with moderate to severe UC.
Aims & Methods
This study evaluated data from two double-blind, Phase 3 trials, INSPIRE (induction: NCT03398148) and COMMAND (maintenance: NCT03398135). During induction, patients were randomised 2:1 to receive intravenous (IV) RZB 1200 mg or placebo (PBO) at Weeks 0, 4, and 8. Those with a clinical response based on Adapted Mayo score were randomised 1:1:1 to subcutaneous (SC) RZB 180 mg, RZB 360 mg, or PBO (RZB withdrawal) every 8 weeks for 52 weeks of maintenance. The proportion of patients achieving normalisation of individual HRQoL outcomes, per literature-based normative value threshold, was assessed at baseline and Weeks 12 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 composite endpoint was determined to evaluate patients achieving normalisation of all HRQoL outcomes. Adjusted treatment differences between RZB and PBO were analysed using Mantel-Haenszel common rate difference. P values were calculated using Cochran-Mantel-Haenszel test and adjusted for strata.
Results
At Week 12, for RZB 1200 mg IV (n=650) vs PBO (n=325), more patients achieved normalisation of each individual HRQoL outcome (p<=0.01) (Table 1). For RZB SC 180 mg (n=179) and 360 mg (n=186), more patients achieved normalisation of FACIT-fatigue, IBDQ, and SF-36 PCS vs PBO at Week 52 (p<=0.05). More patients also achieved normalisation of all WPAI-UC scores with RZB 180 mg SC vs PBO (p<=0.05), excluding overall work impairment. For SF-36 MCS and both EQ-5D-5L scores, more patients achieved normalisation with RZB 180 mg SC vs PBO (p<=0.05), but not with RZB 360 mg SC. Normalisation of the composite HRQoL score was achieved by more patients with all doses of RZB vs PBO at Weeks 12 (RZB 1200 mg: 12.5%; PBO: 4.9%) and 52 (RZB 360 mg: 20.4%; RZB 180 mg: 21.2%; PBO: 10.9%) (p<=0.05).
Table 1. Proportion of patients with UC achieving normalisation of HRQoL outcomes after treatment
HRQoL endpoints at
Weeks 12 and 52,
n (%) | Induction (Week 12)
PBO IV
N=325 | Induction (Week 12)
RZB 1200 mg IV
N=650 | Between group diff. (RZB 1200 mg IV vs PBO)
% [95% CI] | Maintenance (Week 52)
PBO (withdrawal) SC N=183 | Maintenance (Week 52)
RZB 180 mg SC N=179 | Maintenance (Week 52)
RZB 360 mg SC N=186 | Between group diff. (RZB 180 mg SC vs PBO)
% [95% CI] | Between group diff. (RZB 360 mg SC vs PBO)
% [95% CI] |
| FACIT-F score ≥40.1 | 103 (31.7) | 268 (41.3) | 9.7 **
[3.4, 16.0] | 52 (28.4) | 89 (49.7) | 81 (43.6) | 21.3 ***
[11.9, 30.7] | 15.1 **
[5.7, 24.4] |
| IBDQ score ≥170 | 115 (35.4) | 347 (53.3) | 18.1 ***
[11.7, 24.4] | 78 (42.6) | 107 (59.8) | 101 (54.1) | 17.2 ***
[7.5, 27.0] | 12.1 *
[2.3, 22.0] |
WPAI-UC 0%
Overall work imp.a,b
Work time misseda,b
Imp. while workinga,b
Daily activity imp. |
22 (10.9)
86 (42.6)
24 (11.9)
35 (10.8) |
90 (21.7)
237 (57.1)
92 (22.2)
148 (22.8) |
10.9 ***
[5.2, 16.7]
14.6 ***
[6.4, 22.7]
10.4 ***
[4.5, 16.3]
11.9 ***
[7.3, 16.6] |
25 (21.9)
47 (41.2)
27 (23.7)
44 (24.0) |
35 (30.7)
65 (57.0)
40 (35.1)
63 (35.2) |
32 (28.6)
52 (46.4)
34 (30.4)
56 (30.1) |
9.6
[-0.8, 20.1]
14.6 *
[2.5, 26.7]
12.1 *
[1.2, 22.9]
12.0 **
[3.1, 21.0] |
8.6
[-2.4, 19.6]
7.3
[-5.1, 19.6]
9.0
[-2.1, 20.2]
6.0
[-2.8, 14.8] |
| SF-36 PCS ≥50 | 108 (33.2) | 308 (47.4) | 14.4 ***
[8.2, 20.7] | 72 (39.3) | 105 (58.7) | 98 (52.6) | 19.9 ***
[10.2, 29.6] | 14.0 **
[4.2, 23.9] |
| SF-36 MCS ≥50 | 94 (28.9) | 245 (37.8) | 8.9 **
[2.8, 15.1] | 55 (30.1) | 79 (44.1) | 70 (37.9) | 14.3 **
[4.8, 23.8] | 8.3
[-1.0, 17.7] |
| EQ-5D-5L VAS ≥80 | 91 (28.0) | 273 (42.1) | 14.1 ***
[8.0, 20.2] | 61 (33.3) | 80 (44.7) | 73 (39.4) | 12.0 *
[2.5, 21.5] | 6.2
[-3.3, 15.7] |
| EQ-5D-5L Index ≥0.825 | 105 (32.3) | 297 (45.6) | 13.5 ***
[7.3, 19.8] | 65 (35.5) | 91 (50.8) | 74 (40.0) | 16.0 **
[6.1, 25.8] | 4.6
[-5.0, 14.3] |
Composite
HRQoL endpointc | 16 (4.9) | 81 (12.5) | 7.5 ***
[4.1, 11.0] | 20 (10.9) | 38 (21.2) | 38 (20.4) | 10.1 **
[2.7, 17.5] | 9.3 *
[2.1, 16.5] |
*p≤ 0.05. **p≤ 0.01. ***p≤ 0.001. aInduction: PBO IV, N=202; RZB 1200 mg IV, N=415. bMaintenance: PBO (withdrawal) SC, N=114; RZB 180 mg SC, N=114; RZB 360 mg SC, N=112. 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 p values and was adjusted for strata: Advanced Therapy-IR status (yes vs no), baseline steroid use (yes vs no), and baseline Adapted Mayo score (<=7 vs >7).
For maintenance data, the Cochran-Mantel-Haenszel test was used to calculate p values and was adjusted for strata: induction baseline Advanced Therapy-IR status (yes vs no), clinical remission status per Adapted Mayo score at Week 0 (per central read) (yes vs no) and last IV RZB induction dose (600 mg vs 1200 mg vs 1800 mg).
For induction and maintenance data, Mantel-Haenszel common rate difference was used to calculate adjusted treatment differences and 95% CIs.
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; IR, inadequate response; IV, intravenous; MCS, Mental Component Summary; PBO, placebo; PCS, Physical Component Summary; RZB, risankizumab; SC, subcutaneous; SF-36, Short Form 36; UC, ulcerative colitis; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment Questionnaire.<= |
Conclusion
RZB shows greater normalisation of HRQoL compared to PBO, with results seen early during induction and subsequently continued through maintenance. These results indicate that the long-term treatment goal of HRQoL normalisation in patients with moderately to severely active UC may be achievable with RZB.
References
- Turner D, et al. Gastroenterology. 2021;160:1570–83.
Disclosure
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.
Parambir Dulai received research support and/or consulting for AbbVie, Abivax, Adiso, Alimentiv, Bristol Meyer Squibb, Celltrion, Genetench/Roche, Geneoscopy, Janssen, Pfizer, Takeda.
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.
Satoshi Tanida received speaker fees from Kissei, Mitsubishi Tanabe Pharma, Jimro, AbbVie, and Janssen.
Irina Blumenstein has received consultancy honoraria from AbbVie Deutschland, Amgen GmbH, Bristol Myers Squibb, Janssen Cilag GmbH, Fresenius Kabi Deutschland, Pharmacosmos GmbH, Pfizer GmbH, Shire Deutschland GmbH, and Takeda Pharma GmbH; and received honoraria from AbbVie Deutschland, Biogen GmbH, DGVS, Dr. Falk Pharma GmbH, Endoakademie, Ferring Arzneimittel, Fraunhofer, Fresenius Kabi Deutschland, Kompetenznetz Darmerkrankungen, MSD Sharp Dome, Mylan GmbH, Pfizer GmbH, Janssen Cilag GmbH, Shire Deutschland GmbH, and Takeda Pharma GmbH.
Remo Panaccione has received consulting fees, speaker fees, research/educational support from, and/or advisory board member for AbbVie, Abbott, Alimentiv (formerly Robarts), Amgen, Arena, AZ, BI, BMS, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Progenity, Protagonist, Roche, Satisfai, Sandoz, Schering-Plough, Shire, Sublimity, Theravance, Takeda, and UCB.
Yuri Sanchez Gonzalez, Dolly Sharma, Nidhi Shukla, Valencia Remple, Jasmina Kalabic, and Patrick M Hechtare 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.
