Introduction
Due to lack of published data on ustekinumab (UST) use in Greece, REASSURE study aimed to generate real-world evidence (RWE) on treatment persistence, and patient-reported outcomes (PROs) in patients with Crohn’s Disease (CD).
Aims & Methods
REASSURE was a non-interventional, 24-month prospective study of adult (18-80 years old) CD patients newly initiated on UST as 1st, 2nd, or 3rd biologic therapy per the approved label in Greece. Data were collected by routine assessments, including Harvey-Bradshaw Index (HBI), and PROs at baseline (start of UST) and at 4 follow-up visits at 6-month intervals, with a final visit at Month 24 (±2 months) or at treatment discontinuation (whichever occurred first). PROs included the validated Greek version of the Inflammatory Bowel Disease Questionnaire (IBDQ), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale and the Work Productivity and Activity Impairment Questionnaire in Crohn's Disease (WPAI:CD). PROs at 24 months are presented herein.
Results
Between Apr/2019 and Feb/2021, 169 eligible patients were enrolled in 19 Gastroenterology Clinics in Greece. The median (IQR) age at baseline was 45.0 (35.0-54.0) years; of the evaluable patients, 17.5% were overweight, 49.0% had tertiary level of education, and 68.5% were ever-smokers. In terms of employment, 43.4% (72/166) of patients were employed, 29.5% (49/166) unemployed (due to CD in 21.6%; 8/37), 16.3% (27/166) retired (due to CD in 24.0%; 6/25), and 10.8% (18/166) reported other status. Among UST treated patients, 35.5% were bio-naïve (BN) and 64.5% were bio-experienced (BE).
Median (IQR) duration of study participation was 23.9 (18.3-24.7) months (median treatment duration: 24.0 months). At 24 months, 72.8% (123/169) [BN: 76.7% (46/60); BE: 70.6% (77/109)] remained on treatment with UST, while 21.9% (37/169) had discontinued UST after a mean (SD) of 10.2 (6.4) months mainly due to lack/loss of response (15/37), safety issues (10/37), or loss to follow-up (6/37). The proportion of evaluable patients in remission (HBI score 0-4) at 24 months was 87.7% (100/114) [BN: 90.7% (39/43); BE: 85.9% (61/71)].
Baseline median IBDQ (170.0), FACIT-F (34.0), WPAI:CD work productivity loss (WPL) (30.0) and activity impairment scores (30.0) significantly improved (P<0.01) at 24 months, with median changes of 24.0, 6.0, -20.0, and -20.0, respectively, among paired observations. Significant improvements were also noted based on imputed data and in both bio-naive and bio-experienced patients. At 24 months, among patients with paired observations, 56.8% achieved an IBDQ response (≥16-point increase), 59.3% a significant FACIT-F improvement (≥4-point increase) and 68.4% a clinically meaningful improvement in WPL (≥7-point decrease) from baseline. Further details on baseline characteristics and 24-month PROs are shown in Table 1.
| Table 1: Baseline characteristics and 24-month PROs |
| Overall (N=169) | Bio-naïve (1L) (N=60) | Bio-experienced (N=109) |
| Time from CD diagnosis to UST initiation, median (IQR), years | 7.0 (1.8, 13.0) | 1.3 (0.3, 6.2) | 10.1 (5.9, 15.9) |
Baseline characteristics, % (n/N)
Age ≤50 years
Females
Employed (full-time or part-time)
At least 1 comorbidity
Stricturing and/or penetrating disease
Extraintestinal manifestations
Starting UST maintenance dosage: 90 mg SC Q8W |
62.7 (106/169)
50.9 (86/169)
43.4 (72/166)
55.0 (93/169)
43.2 (70/162)
36.5 (61/167)
89.9 (152/169) |
51.7 (31/60)
41.7 (25/60)
55.9 (33/59)
55.0 (33/60)
33.3 (19/57)
31.7 (19/60)
83.3 (50/60) |
68.8 (75/109)
56.0 (61/109)
36.4 (39/107)
55.0 (60/109)
48.6 (51/105)
39.3 (42/107)
93.6 (102/109) |
IBDQ at month 24
Response (change ≥16 points), % (n/N), as observed
Response (change ≥16 points), % (n/N), imputed
Median/mean change from baseline (IQR/SD), as observed
Median change from baseline (IQR/SD), imputed |
56.8 (63/111)
44.2 (73/165)
24.0 (5.0, 52.0)w
9.0 (0.0, 36.0)w |
60.5 (26/43)
49.2 (29/59)
33.0 (39.6)T
14.0 (-1.0, 47.0)w |
54.4 (37/68)
41.5 (44/106)
25.7 (35.6)T
8.0 (0.0, 36.0)w |
FACIT-F at month 24
Significant improvement (≥4 points), % (n/N), as observed
Significant improvement (≥4 points), % (n/N), imputed
Median/mean change from baseline (IQR/SD), as observed
Median/mean change from baseline (IQR/SD), imputed |
59.3 (67/113)
47.9 (80/167)
6.0 (0.0, 15.0)w
2.0 (0.0, 12.0)w |
62.8 (27/43)
53.3 (32/60)
9.1 (14.3)T
4.0 (0.0, 14.5)w |
57.1 (40/70)
44.9 (48/107)
7.2 (12.1)T
1.0 (0.0, 10.0)w |
Activity impairment at month 24 (based on WPAI:CD)
Median change from baseline (IQR), as observed
Patients completing WPAI:CD at both baseline and 24 months
Median change from baseline (IQR), imputed
Patients completing WPAI:CD at baseline |
-20.0 (-40.0, 0.0)w
N=113
-10.0 (-40.0, 0.0)w
N=166 |
-20.0 (-40.0, 0.0)w
N=43
-10.0 (-30.0, 0.0)w
N=60 |
-20.0 (-40.0, 0.0)w
N=70
-5.0 (-40.0, 0.0)w
N=106 |
Work productivity loss at month 24 ( WPAI:CD)
CMI (decrease of ≥7 points), % (n/N), as observed
CMI (decrease of ≥7 points), % (n/N), imputed
Median change from baseline (IQR), as observed
Median change from baseline (IQR), imputed |
68.4 (26/38)
53.8 (28/52)
-20.0 (-56.8, 0.0)w
-10.0 (-30.0, 0.0)w |
77.8 (14/18)
63.6 (14/22)
-20.0 (-60.0, -10.0)w
-20.0 (-56.9, 0.0)w |
60.0 (12/20)
46.7 (14/30)
-10.0 (-35.8, 0.0)w
0.0 (-21.6, 0.0)w |
| Data imputation was performed using last observation carried forward analysis. For change from baseline, median (IQR) or mean (SD) is displayed, depending on p-value of normality (< or ≥0.05, respectively). Abbreviations: 1/2/3L: First/Second/Third Line; CD: Crohn's Disease; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; IBDQ: Inflammatory Bowel Disease Questionnaire; IQR: Interquartile Range; IV: intravenous; N: number of patients with available data; n, number of patients with variable; ns, not statistically significant; PRO, Patient Reported Outcome; Q8W: every 8 weeks; SC: subcutaneous; SD: Standard Deviation; T: T-test p-value of change <0.01, indicating statistical significance; UST: ustekinumab; W: Wilcoxon signed-rank test p-value of change <0.01, indicating statistical significance; WPAI:CD: Work Productivity and Activity Impairment Questionnaire in Crohn's Disease, CMI: Clinically meaningful improvement. |
Conclusion
These data provide RWE on the beneficial effect of UST on health-related quality of life, fatigue, and work productivity in both bio-naïve and bio-experienced CD patients in Greece.
Disclosure
This study was sponsored by Janssen - Cilag, Greece.
Giorgos Bamias Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper, BMS; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda, Janssen.
Gerassimos J. Mantzaris has received consultant and/or speaker fees from AbbVie, MSD, Celtrion,Ferring, Aenorasis, Janssen, Pfizer, Takeda, Falk Pharma, and Vianex and research support from AbbVie, Ferring, MSD, and Vianex
Maria Tzouvala has received clinical research funding from Janssen-Cilag Pharmaceuticals SACI, Takeda HELLAS SA, AbbVie Pharmaceuticals S.A. Consulting and/or speaking fees MSD Sharp& Dohme, Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen. Advisory boards: Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen
Dimitrios Christodoulou has received consulting and speaking fees for Janssen, MSD, Galenica. Advisory Board for Galenica
Ioannis Koutroubakis has received clinical research funding: Abbvie, Faran, Ferring, Pfizer, Viatris, Vianex, Vifor, Unipharma. Consulting and/or speaking fees Abbvie, Genesis, Janssen, MSD, Takeda, Vianex. Advisory boards: Abbvie, Janssen, MSD, Pfizer, Takeda, Vianex
Christos Liatsos has received clinical research funding from: Janssen, and consulting and/or speaking fees from: MSD, Pfizer, Boston SCI, Amgen, Galenica.
Georgios Papatheodoridis Clinical research funding: Abbvie, Gilead, Takeda, Vianex. Consulting and/or speaking fees: Abbvie, Astra-Zeneca, BioARS Therapeutics, Elpen, Genesis, Gilead, GlaxoSmithKline, Ipsen, Novo Nordisk, Roche, Sobi. Advisory boards: Abbvie, Astra-Zeneca, Albireo, Amgen, Galenica, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Novo Nordisk, Roche, Takeda
Dr Katsanos Konstantinos received honoraria for consulting services (educational services, scientific articles, participation in Advisory Boards, clinical trials, lecture fees, other) from the companies as follows:AbbVie, AMGEN, ENORASIS, Epsilon Health, Ferring, Genesis, Grifols S.A., JANSSEN, MSD, Mylan, Shire and Takeda.
Evanthia Zampeli has received clinical research funding: Janssen, TAKEDA, ABBVIE. Consulting and/or speaking fees: Janssen, TAKEDA, BMS, AMGEN, MYLAN. Advisory boards: BMS, GALENICA
Georgios Germanidis has received clinical research funding from Janssen.
Konstantinos Soufleris Consulting and/or speaking fees: AbbVie, Janssen, MSD, Pfizer, Takeda. Clinical research funding:Pfizer. Advisory board: BMS, Galenica.
Matina-Lydia Chatzinikolaou has received consulting fees from Abbvie, Takeda, Amgen, Ferring, Janssen
George Kokkonis has received clinical Research funding from Janssen and speaking fees from Janssen and Amgen
Alexandros Boubonaris has served as advisory board member for Amgen, Takeda
Marios Giakoumis has received clinical research funding from Janssen
Artemis Trikola has received clinical research funding from Janssen
George Michalopoulos has received speaker fees: Takeda, MSD, , Abbvie, Jannsen, Pfizer, Amgen
Vasileios Delis, Konstantina Paraskeva, Theodosios Sdonas, Athanasia Tasovasili, Evgenia Papathanasiou, Maria Palatianou, Andreas Nakos, Nikoletta Mathou, George Kalopitas, Panagiotis Giannelis, Kalliopi Foteinogiannopoulou, Konstantina Chalakatevaki, Eleni Beka, Evmorfia Karamintziou, Eleftheria Giannakoulopoulou have no conflicts to disclose.
Konstantinos Thomopoulos, Stergios Vradelis, Andreas Protopapas, Ioannis Pachiadakis, Ioannis Goulis, Pantelis Karatzas, George Theocharis, George Tribonias, Angeliki Machaira, Nikolaos Kyriakos, Adonis Protopapas, Konstantinos Fasoulas, Evdoxia Stergiou and Charilaos Taloumtzis have not disclosed any conflicts
Spyridon Michopoulos has received clinical research funding from Janssen, Takeda, BMS, consulting and/or speaking fees from Takeda, and has served as advisory board member for Takeda.
Christos Gkamaloutsos, Ioannis Kanistras and Aikaterini Mpartsea are employees of Janssen - Cilag, Greece