Introduction
Endoscopic healing is an important treatment goal for patients (pts) with Crohn’s disease (CD).1 Herein, the relationships between endoscopic healing and achievement of long-term patient reported outcomes (PROs) and occurrence of CD-related hospitalization were assessed in pts with moderate to severe CD treated with risankizumab (RZB) maintenance therapy from the FORTIFY trial.
Aims & Methods
In FORTIFY, pts who had clinical response to RZB induction2 received 52 weeks (wks) of maintenance therapy (subcutaneous 180mg or 360mg every 8wks) in substudy 13 and continued receiving RZB as per their treatment assignment in the open-label extension (OLE) substudy 3. This analysis included pts who completed 2 years (y) of RZB in the OLE (cumulative RZB treatment of 3 years including 52wks in substudy 1) (cutoff date: 01MAR2024). Clinically meaningful improvements in PROs were assessed, including Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total score), IBDQ remission (total score ≥170-points), improvement in 36-Item Short Survey (SF-36) physical component score (PCS, ≥4.1-points) and mental component summary (MCS, ≥3.9-points), EuroQol-5D questionnaire visual analog scale (EQ-5D-5L VAS; ≥9.2-points), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) response (≥9-points). Exposure-adjusted occurrence of CD-related hospitalizations was also assessed as incidence rates (events/100 patient-y) from OLE wk52 to wk152. The proportion of pts who achieved each outcome at wk152 were compared based on their achievement of wk52 endoscopic response, endoscopic remission, or ulcer-free endoscopy vs not (endpoint definitions in Table footnote) using chi-square testing. Pts with missing outcomes were considered nonresponders. Endoscopies were scored by a central reviewer. Long-term safety of RZB has been reported.2
Results
Of the 257 pts included in the analysis, 134 (52.1%), 99 (38.5%), and 79 (30.7%) pts achieved wk52 endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively. Significantly more pts who achieved wk52 endoscopic response also achieved IBDQ response and remission, SF36 PCS and MCS response, and improvement in FACIT-F and EQ-5D-5L VAS scores at wk152 (P≤.0001 for all comparisons) vs pts who did not achieve wk52 endoscopic response (Table). Similar results were observed for pts who achieved wk52 endoscopic remission (P≤.01) and pts who achieved wk52 ulcer-free endoscopy (P≤.02, except for SF36 MCS response) at wk152. CD-related hospitalizations from wk56 to wk152 were significantly lower for pts who achieved wk52 endoscopic remission and endoscopic response and numerically lower for pts who achieved wk52 ulcer-free endoscopy, vs not.
Parameter
| Endoscopic responsea (Yes), N=134
| Endoscopic responsea (No),
N=123
| P value
| Endoscopic remissionb (Yes),
N=99
| Endoscopic remissionb
(No),
N=158
| P value
| Ulcer-free endoscopyc (Yes),
N=79
| Ulcer-free endoscopyc (Yes),
N=178
| P value
|
PROs at Week 152 (Week 96 of FORTIFY OLE)
n/N (%)
IBDQ responsed
IBDQ remissione
SF36 PCS responsef
SF36 MCS responseg
EQ-5D-5L VASh
FACIT-F responsei
Exposure adjusted occurrence of CD-related hospitalizations from maintenance week 0 to week 152j
n/N
(%)
[time in patient-years]
incidence rate
|
100/134
(74.6)
84/134
(62.7)
90/134
(67.2)
80/134
(59.7)
94/134
(70.2)
106/134
(79.1)
6/134
(4.5)
[395.0773]
1.52
|
55/123
(44.7)
46/123
(37.4)
53/123
(43.1)
43/123
(35.0)
54/123
(43.9)
65/123
(52.8)
13/123
(10.6)
[257.8864]
5.04
|
<.0001
<.0001
.0001
<.0001
<.0001
<.0001
.0213
|
71/99
(71.7)
65/99
(65.7)
67/99
(67.7)
57/99
(57.6)
67/99
(67.7)
77/99
(77.8)
4/99
(4.0)
[292.5174]
1.37
|
84/158
(53.2)
65/158
(41.1)
76/158
(48.1)
66/158
(41.8)
81/158
(51.3)
94/158
(59.5)
15/158
(9.5)
[360.4463]
4.16
|
.0031
.0001
.0021
.0136
.0096
.0025
.0282
|
60/79
(76.0)
51/79
(64.6)
55/79
(69.6)
45/79
(57.0)
54/79
(68.4)
63/79
(79.8)
5/79
(6.3)
[234.1136]
2.14
|
95/178
(53.4)
79/178
(44.4)
88/178 (49.4)
78/178
(43.8)
94/178 (52.8)
108/178
(60.7)
14/178
(7.9)
[418.8501]
3.34
|
.0006
.0028
.0027
.0517
.0200
.0028
.3561
|
Abbreviations: BL, baseline; CD, Crohn’s disease; EQ-5D-5L VAS, EuroQol-5D questionnaire visual analog scale; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; IBDQ, inflammatory bowel disease questionnaire; MCS, mental component score; OLE, open-label extension; PCS, physical component score; PROs, patient reported outcomes; SES-CD, Simple Endoscopic Score for CD; SF-36, 36-Item Short Form Survey.
aEndoscopic response: decrease in the SES-CD > 50% from induction BL (or for patients with isolated ileal disease and a BL SES-CD = 4, ≥ 2 point reduction from induction BL).
bEndoscopic remission: SES-CD ≤ 4, ≥ 2-point reduction from BL, and no subscore > 1 in any individual variable.
cUlcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in patients with SES-CD ulcerated surface subscore ≥ 1 at induction BL.
dIBDQ response: ≥ 16-point IBDQ total point improvement from the induction BL.
eIBDQ remission: IBDQ total score ≥ 170 points.
fSF-36 PCS response: change ≥ 4.1 from BL.
gSF-36 MCS response: change ≥ 3.9 from BL.
hEQ-5D-5L VAS: change ≥ 9.2 from BL.
iFACIT-F response: change ≥ 9 from BL.
jIncidence rate differences (95% CI and P value) between the comparison groups were based on the normal approximation to poisson distribution.
Bold font denotes a P value ≤ .05.
|
Conclusion
A significantly greater proportion of pts achieved 3y sustained improvement in PROs when they achieved endoscopic outcomes at 52wks of RZB maintenance treatment. Achievement of endoscopic outcomes at 52wks also resulted in fewer CD-related hospitalizations through 152wks when continuing active therapy, pointing to favorable long-term outcomes of disease.
References
Turner D, et al. Gastroenterology. 2021;160:1570-83.
Ferrante M, et al. J Crohns Colitis. 2021; 15(12):2001-2010.
Disclosure
Christopher Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.
Brian G Feagan has served as a consultant or received speaker’s fees from Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharmaceuticals, gIcare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharmaceuticals, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Kyowa Hakko Kirin Co, Lexicon, Lilly, Lycera, Merck, Mesoblast, Millennium, Nektar, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Receptos, Roche/Genentech, Salix Pharmaceuticals, Serono, Shire, Sigmoid Pharma, Synergy Pharmaceuticals, Takeda, Teva Pharmaceuticals, TiGenix, Tillotts, UCB, Vertex Pharmaceuticals, VHsquared, Warner Chilcott, Wyeth, Zealand Pharma, and Zyngenia, and has received research support from Abbott/AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, and UCB.
Peter Bossuyt received financial support for research from AbbVie, Amgen, Celltrion, Mylan, Pfizer, and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly, and Takeda; and advisory board fees from AbbVie, Arena Pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros.
Vipul Jairath has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.
Namita Joshi, Nidhi Shukla, Kristina Kligys, Ari Stromberg,andJameson Crowley are full-time employees/contractor of AbbVie and may own AbbVie stock or options.
Acknowledgments
AbbVie funded this study (NCT03105102) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial.
Medical writing support was provided by Stephanie Parsons, PhD, an employee of AbbVie. Editorial support was provided by Amy Kuang, an employee of AbbVie.
