Introduction
PRA023 is a humanized monoclonal antibody against tumor necrosis factor–like cytokine 1A (TL1A), a key pro-inflammatory cytokine and pro-fibrosis regulator, in development for inflammatory bowel diseases. In a phase 2 double-blind, placebo-controlled study (ARTEMIS-UC) assessing the efficacy and safety of PRA023 induction treatment in adults with moderately to severely active ulcerative colitis (UC), a significantly greater proportion of patients who received PRA023 achieved the primary endpoint of clinical remission after 12 weeks. This post hoc analysis assessed the impact of PRA023 on health-related quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ-32).
Aims & Methods
Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore of ≥2, rectal bleeding subscore of ≥1, and history of insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies (≤4 advanced agents from ≤3 classes allowed) were stratified by prior biologic exposure and genetic-based diagnostic status and randomized 1:1 to placebo or intravenous PRA023 (1000 mg on day 1, and 500 mg at weeks 2, 6, and 10). IBDQ outcomes measures include: IBDQ response (score of ≥16-point from baseline), IBDQ remission (total score ≥170), and mean change from baseline in total and domain scores after 12 weeks of induction therapy. Score changes from baseline were compared among treatment groups, and the impact of prior advanced therapy exposure on IBDQ remission was assessed. Higher scores represent better quality of life.
Results
Of the 135 patients in the study, 60/67 (89.6%) in the placebo arm and 68/68 (100%) in the PRA023 arm completed the 12-week induction period. Baseline characteristics were similar between the treatment groups. Significantly greater proportions of patients in the PRA023 group achieved IBDQ response (82.4% PRA023 vs 49.3% placebo, ∆33.1%, p<0.0001) and IBDQ remission (51.5% PRA023 vs 19.4% placebo, ∆32.1%, p=0.0001) at week 12. Prior advanced therapy use did not affect the placebo-adjusted proportion of patients experiencing IBDQ remission in those who received PRA023 (Δ34.4% vs Δ30.0%, respectively, for prior and no prior advanced therapy). The total IBDQ score and all IBDQ domain subscores (bowel symptoms, systemic symptoms, emotional function, and social function) were significantly improved after 12 weeks of PRA023 induction treatment compared to placebo (Table 1).
Table 1. Inflammatory Bowel Disease Questionnaire (IBDQ) Outcomes with PRA023 Induction Therapy
| IBDQ outcomes | Placebo | PRA023 | % Difference vs placebo
(95% CI) | P value |
| IBDQ response (%, n/N)†‡ | 49.3 (33/67) | 82.4 (56/68) | 33.1 (17.2–46.8) | <0.0001 |
| IBDQ remission (%, n/N)‡ | 19.4 (13/67) | 51.5 (35/68) | 32.1 (16.0–45.9) | 0.0001 |
| -Prior advanced therapy | 18.8 (6/32) | 53.1 (17/32) | 34.4 (10.9–53.1) | - |
| -No prior advanced therapy | 20.0 (7/35) | 50.0 (18/36) | 30.0 (7.8–48.4) | - |
Change in IBDQ scores from BL, mean±SD
-Total score
| 20.8±37.59
| 48.6±34.85
| 26.8 (14.6–38.9)
| <0.0001
|
| -Bowel symptoms subscore | 7.1±12.27 | 17.2±11.79 | 9.4 (5.3–13.4) | <0.0001 |
| -Systemic symptoms subscore | 3.0±5.97 | 7.0±6.56 | 4.0 (2.0–6.0) | 0.0002 |
| -Emotional function subscore | 6.6±14.59 | 16.1±13.25 | 8.9 (4.3–13.5) | 0.0002 |
| -Social function subscore | 4.1±7.74 | 8.2±7.38 | 4.4 (2.0–6.8) | 0.0004 |
†Prespecified secondary endpoint.
‡Nonresponder imputation was applied to response and remission endpoints.
Abbreviations: BL, baseline; IBDQ, Inflammatory Bowel Disease Questionnaire.
P values are nominal except IBDQ response.
Conclusion
PRA023 significantly improved quality-of-life measures in patients with moderately to severely active UC, regardless of prior advanced therapy use. The greatest benefits were reported in the bowel symptoms and emotional function domains.
Disclosure
LPB has served as a consultant for or has received fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Eli Lilly and Company, Enterome, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Hikma, Index Pharmaceuticals, Inotrem, Janssen, MSD, Mylan, Oppilan Pharma, OSE Immunotherapeutics, Nestlé, Norgine, Roche, Pandion Therapeutics, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, sterna biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tillotts Pharma, and Vifor; has received grants from AbbVie, Fresenius Kabi, MSD, and Takeda; and has stock options from CTMA.
BES has served as a consultant for or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharma, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, GSK, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio and has received stock options from Ventyx Biosciences.
SD has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor and lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
DTR has served as a consultant for AbbVie, AltruBio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Chronicles, Corp/Syneos, ClostraBio, Connect Biopharma, Eco R1, Eli Lilly and Company, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido, Pfizer, Prometheus Biosciences, Reistone Biopharma, Seres Therapeutics, Takeda, Target RWE, and Trellus Health and has received grant support from Takeda, Helmsley Charitable Trust, and the Gastro-Intestinal Research Foundation.
DDN, QD, AM, and BD are employees and shareholders of Prometheus Biosciences.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, BIOJAMP, Bristol Myers Squibb, Celltrion Healthcare, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Prometheus Biosciences, Roche, and Sanofi; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; and research support from Ferring and Pfizer.
TER has been a speaker for Takeda Pharmaceuticals, Janssen, Pfizer, Bristol Myers Squibb, and Abbvie; has served on advisory boards for AbbVie, Ardelyx, Arena, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Ferring, Genentech/Roche, Gilead, Intercept, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Sanofi, and Takeda; and has been a shareholder for Iterative Scopes.
RP has been a consultant for Abbott, AbbVie, Abivax, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and Company, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB; has received speakers fees from AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; and has served on advisory boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Ventyx.
