Introduction
Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). Previous analyses of data from the phase 2b/3 SELECTION trial (NCT02914522) demonstrated that FIL 200 mg (FIL200) improved health-related quality of life (HRQoL) and led to comprehensive disease control (comprising clinical, biomarker, HRQoL and endoscopic improvements) in patients with UC.1
Aims & Methods
We evaluated individual Inflammatory Bowel Disease Questionnaire (IBDQ) item data from SELECTION to assess which items drive the benefits of FIL treatment. In SELECTION, adults with moderately to severely active UC were randomized 2:2:1 to receive FIL200, FIL 100 mg or PBO once daily for 11 weeks in Induction Studies A and B (biologic-naive and -experienced patients, respectively). Patients who responded to FIL were rerandomized 2:1 to continue their induction FIL dose in the 47-week Maintenance Study. In this post hoc analysis, standardized effect sizes (SES) were calculated to evaluate the relative magnitude of the difference in mean scores of individual IBDQ items at week 10 (W10) between FIL200 versus PBO-treated patients, and at week 58 (W58) between patients who continued FIL200 treatment (FIL200→FIL200) versus those who were rerandomized to PBO (FIL200→PBO). SES were also calculated for the mean change in score of individual IBDQ items from baseline to W10, and from maintenance baseline to W58. SES were categorized by Cohen’s thresholds (‘trivial’ [<0.2]; ‘small’ [≥0.2–<0.5]; ‘moderate’ [≥0.5–<0.8]; and ‘large’ [≥0.8]). A last observation carried forward imputation approach was used for missing data.
Results
At W10, patients treated with FIL200 overall (n=506) had improvements in all individual IBDQ items versus those treated with PBO (n=277) and had moderate to large increases from baseline (SES ≥0.5) in all individual IBDQ items. The IBDQ items with the five largest SES for FIL200 versus PBO at W10 (analysed by induction study), and for FIL200→FIL200 (n=199) versus FIL200→PBO (n=98) at W58 are summarized in the Table. FIL200 treatment consistently resulted in the largest benefits in items related to pain (‘abdominal pain’ and ‘abdominal cramps’), ability to engage socially (‘satisfied with life’, ‘depressed or discouraged’, ‘social engagement’ and ‘problems with activities’) and bowel urgency (‘loose bowel movements’ and ‘finding a washroom’) versus PBO at W10, and versus FIL200→PBO at W58
Table. Top five individual IBDQ item scores ranked by SES for FIL200 versus PBO groups at W10 and FIL200→FIL200 versus FIL200→PBO groups at W58.
| FIL200 group – end of induction (W10) |
| Biologic-naive (n=245) | Biologic-experienced (n=261) |
| IBDQ items | W10 score, mean (SD)
| SES vs PBO | Change in mean score from baseline, mean (SD) | SES vs baseline | IBDQ item | W10 score, mean (SD)
| SES vs PBO | Change in mean score from baseline, mean (SD) | SES vs baseline |
Social engagement
Satisfied with life
Depressed or discouraged
Abdominal cramps
Felt angrya | 5.8 (1.4)
4.6 (1.2)
5.4 (1.3)
5.5 (1.4)
5.6 (1.3) | 0.62
0.62
0.58
0.56
0.55 | 1.8 (1.9)
1.3 (1.5)
1.6 (1.7)
1.8 (1.6)
1.6 (1.7) | 0.82
0.73
0.78
0.99
0.81 | Loose bowel movements
Problems with activities
Abdominal pain
Bowel movement frequency
Rectal bleeding | 4.1 (1.9)
4.7 (1.8)
5.1 (1.6)
5.2 (1.9)
5.0 (2.0) | 0.72
0.64
0.63
0.62
0.62 | 1.9 (1.9)
1.9 (1.9)
1.6 (1.6)
2.2 (2.1)
2.6 (2.1) | 0.88
0.89
1.02
0.83
1.01 |
| FIL200→FIL200 group (n=199) – end of maintenance (W58) |
| IBDQ item | W58 score,
mean (SD) | SES vs FIL200→PBO | Change in mean score from maintenance baseline,
mean (SD) | SES vs maintenance baseline |
Bowel movement frequency
Rectal bleeding
Abdominal cramps
Problems with activities
Finding a washroom | 6.3 (1.4)
6.3 (1.4)
6.2 (1.1)
6.0 (1.3)
6.1 (1.4) | 0.57
0.55
0.47
0.44
0.41 | 0.4 (1.6)
0.2 (1.6)
0.5 (1.4)
0.6 (1.4)
0.4 (1.4) | 0.19
0.10
0.28
0.42
0.27 |
aThe items ‘felt angry’ and ‘irritable’ had the same SES versus PBO; however, ‘felt angry’ had the larger change in mean score from baseline.
SES for comparison with PBO/FIL200→PBO was calculated as follows: mean differences/pooled SD.
SES for comparison with baseline was calculated as follows: mean change from baseline/(SD/√(2*(1−r))).
SES were categorized by Cohen’s thresholds (‘trivial’ [<0.2], ‘small’ [≥0.2–<0.5], ‘moderate’ [≥0.5–<0.8] and ‘large’ [≥0.8]).
FIL200→FIL200 treatment group = patients who responded to FIL200 during induction and were rerandomized to continue FIL200 during maintenance.
FIL200→PBO treatment group = patients who responded to FIL200 during induction and were rerandomized to PBO during maintenance.
FIL200, filgotinib 200 mg; IBDQ, Inflammatory Bowel Disease Questionnaire; PBO, placebo; r, Pearson correlation coefficient; SD, standard deviation; SES, standardized effect size; W10, week 10; W58, week 58. |
Conclusion
FIL200 treatment provides improvements in HRQoL versus PBO, with large SES seen for most IBDQ items, and the greatest improvements in items related to pain, social engagement and bowel urgency over 58 weeks. This analysis reveals the specific IBDQ items that drive the benefits to HRQoL of FIL and adds further evidence to that showing that FIL contributes to restoration of health through comprehensive disease control for patients with UC.1
References
1. Schreiber S et al. J Crohns Colitis 2023; https://doi.org/10.1093/ecco-jcc/jjad018
Disclosure
BF reports grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; and personal fees from Ablynx, ActoGeniX, AdMIRx, Inc., Akebia Therapeutics, Inc., Allergan, Atlantic Pharmaceuticals, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, Eli Lilly, enGene, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, gIcare Pharma, Gilead, Given Imaging, Gossamer Bio, GSK, Inception IBD, Inc., Ironwood Pharmaceuticals, Japan Tobacco Company, Kyowa Hakko Kirin Co. Ltd, Lexicon Pharmaceuticals, Lycera, Mesoblast, Millennium Pharmaceuticals, MSD, Nestlé, Nextbiotix, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus Therapeutics and Diagnostics, Protagonist, Qu Biologics, Salix Pharmaceuticals, Shire, Sienna Biopharmaceuticals, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts Pharma, UCB, Vertex Pharmaceuticals, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand Pharma and Zyngenia.
SV reports grants from AbbVie, Galapagos, J&J, Pfizer and Takeda; consulting and/or speaker fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia Biologics, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma and Zealand Pharma.
LP-B reports speaking fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech, Gilead, Janssen Pharmaceuticals, Medac Pharma, MSD, Pfizer, Sandoz, Takeda, Tillotts Pharma, Viatris and Vifor Pharma;grants from Celltrion, Fresenius Kabi and Takeda; and consulting fees from AbbVie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, CONNECT Biopharma, Cytoki Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, H.A.C. Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, medac Pharma, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharmaceutical, OSE