Introduction

Risankizumab (RZB), a monoclonal antibody neutralizing interleukin (IL)-23p19, was evaluated for efficacy and safety of induction therapy in patients with moderately to severely active ulcerative colitis (UC) in a large phase 3 trial, INSPIRE (NCT03398148).

Aims & Methods

Eligible patients (18-80 years) with moderately to severely active UC (Adapted Mayo score of 5 – 9 points) and an endoscopic subscore of 2-3 (per central review) were enrolled. Patients were required to have a diagnosis of UC for at least 3 months prior to baseline, and demonstrated intolerance or inadequate response to conventional and/or advanced therapies (biologics, JAK inhibitors, and S1P receptor modulators). Patients (N=975) were randomized 2:1 to receive either RZB 1200 mg intravenously (IV) or placebo (PBO) at Weeks (Wks) 0, 4, and 8, stratified by baseline corticosteroid use (yes vs no), baseline Adapted Mayo score (≤ 7 vs > 7), and the number of advanced therapy failures (0, 1, >1). The primary endpoint was clinical remission (per Adapted Mayo score) at Wk 12 (see Table 1 for definitions). Key, ranked secondary endpoints included clinical response, endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI), and histologic-endoscopic mucosal remission (HEMR), which were measured at Wk 12, unless otherwise noted.

Results

Baseline characteristics were similar between treatment groups. Significantly more patients receiving RZB achieved clinical remission vs PBO (20.3% vs 6.2%, adjusted treatment difference 14.0% [95% CI, 10.0%-18.0%], P<.00001). All ranked secondary endpoints were met. RZB attained higher rates of clinical response (per Adapted Mayo score at Wk 12 and per Partial Adapted Mayo score at Wk 4), endoscopic improvement, endoscopic remission, HEMI, and HEMR compared to PBO (P<.00001 for all endpoints). Adverse event (AE) rates were 42.1% in RZB vs 49.7% PBO, serious AEs (2.3% vs 10.2%), severe AEs (2.5% vs 10.2%), AEs leading to discontinuation of study drug (0.6% vs 3.7%), and serious infections (0.6% vs 1.2%) were numerically lower in the RZB arm. No adjudicated major adverse cardiovascular events, adjudicated anaphylaxis, or serious hepatic events were reported. One death occurred in the RZB group due to COVID-19 pneumonia.

Endpoints	PBO IV N=325 % h	RZB 1200 mg IV N=650% h	Treatment Difference vs PBO % [95% CI]
Primary Endpoint: Clinical remission per Adapted Mayo scorea Overall Advanced Therapy-naïve Advanced Therapy-IR	6.2 N=155; 8.4 N=170; 4.3	20.3 N=317; 29.7 N=333; 11.4	14.0 [10.0, 18.0]*** 21.3 [14.6, 27.9] 7.2 [2.6, 11.8]
Secondary Endpoints
Clinical response per Adapted Mayo scoreb	35.7	64.3	28.6 [22.3, 34.8]***
Clinical response per Partial Adapted Mayo score, Week 4c	30.5	52.2	21.8 [15.6, 28.1]***
Endoscopic improvementd	12.1	36.5	24.3 [19.3, 29.4]***
Endoscopic remissione	3.4	10.6	7.2 [4.2, 10.2]***
Histologic-endoscopic mucosal improvement (HEMI)f	7.7	24.5	16.6 [12.3, 21.0]***
Histologic-endoscopic mucosal remission (HEMR)g	0.6	6.3	5.6 [3.5, 7.7]***
All patients in this dataset were included here within the ITT population. Endpoints were assessed at Week 12 unless otherwise noted. a. Clinical Remission per Adapted Mayo score: Stool frequency subscore ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1 without friability b. Clinical Response per Adapted Mayo: Decrease from baseline ≥ 2 points and ≥ 30%, in addition to a decrease in RBS ≥ 1 or an absolute rectal bleeding score (RBS) ≤ 1 c. Clinical Response per Partial Adapted Mayo: Decrease from baseline ≥ 1 point and ≥ 30% a decrease in RBS ≥ 1 or an absolute RBS ≤ 1 d. Endoscopic Improvement: Endoscopic subscore of 0 or 1 without friability e. Endoscopic Remission: Endoscopic subscore = 0 f. Histologic-Endoscopic Mucosal Improvement (HEMI): Endoscopic subscore of 0 or 1 without friability and Geboes score ≤ 3.1 g. Histologic-Endoscopic Mucosal Remission (HEMR): Endoscopic subscore of 0 and Geboes score < 2.0 h. Results are based on non-responder imputation incorporating multiple imputation (NRI-MI) to handle missing data due to COVID-19 or due to geopolitical conflict in Ukraine or surrounding areas. ***P-value <.00001 vs PBO. P-value for treatment difference between RZB 1200 mg IV and PBO, using Cochran-Mantel­Haenszel (CMH) test for categorical endpoints, controlling for stratification factors. IR, inadequate response

Conclusion

In patients with moderately to severely active UC, RZB was superior to PBO as an induction therapy for clinical remission and all secondary clinical, endoscopic, and endoscopic-histologic endpoints. RZB was well-tolerated, and no new safety risks were observed.

Disclosure

Edouard Louis has received research grants from Janssen,Pfizer,andTakeda; received educational grants from AbbVie,Janssen,MSD,andTakeda; received speaker fees from AbbVie, Falk,Ferring,Hospira,Janssen,MSD,Pfizer,andTakeda; served on advisory boards for AbbVie, Arena,Celgene,Ferring,Galapagos,Gilead,Hospira,Janssen,MSD,Pfizer,andTakeda;andserved as a consultant for AbbVie.Remo Panaccione has received consulting fees, speaker fees, and researchsupportfromAbbVie,Abbott,Alimentiv(formerlyRobarts),Amgen,ArenaPharmaceuticals,AstraZeneca,BristolMyersSquibb,BoehringerIngelheim,Celgene,Celltrion,CosmosPharmaceuticals,Eisai,Elan, EliLilly,Ferring,Galapagos,Genentech,GileadSciences,GlaxoSmithKline,Janssen,Merck,Mylan,OppilanPharma,PandionPharma,Pfizer,Progenity,ProtagonistTherapeutics,Roche,SatisfaiHealth,Sandoz,Schering-Plough,Shire,Sublimity Therapeutics,TheravanceBiopharma,UCB,andTakedaPharmaceuticals.GarethParkeshas receivedconsultancyfeesfromAbbVie,Allergan,BMS,Celltrion,Ferring,Galapagos,Janssen,Napp Pharmaceuticals,Pfizer,SorrisoPharmaceuticals,Takeda,andTillotts.Receivedresearch fundingfrom AbbVie,andTakeda and is a director and shareholder in Ampersand Health.Laurent Peyrin-BiroulethasreceivedconsultingfeesfromAbbVie,Alimentiv,AlmaBioTherapeutics,Amgen, Applied Molecular Transport,Arena,Biogen,BMS,Celltrion,CONNECTBiopharm,CytokiPharma, Enthera,Ferring,FreseniusKabi,Galapagos,Genentech,Gilead,GossamerBio,GSK,HAC-Pharma, IAGImage Analysis,Index Pharmaceuticals,Inotrem, Janssen, Lilly,Medac, Mopac, Morphic, MSD,Norgine,Novartis,OM Pharma,ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune,Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; grants from Takeda, Fresenius Kabi, Celltrion; and lecture fees from: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac.Marc Ferrante has received speaker and/or consultant fees from AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Dr Falk, Eli Lilly, Ferring, Janssen-Cilag, Lamepro, Medtronic, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, Thermo Fisher, Truvion Healthcare and Viatris; Research Grants: AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda, and Viatris.Ken Takeuchi has received consulting fees from Thermo Fisher Diagnostics K.K.; has received research grants from AbbVie and Takeda; and has served as a speaker for AbbVie, Celltrion Healthcare, EA Pharma, Janssen, Kyorin, Mochida, Takeda, Tanabe Mitsubishi, and Zeria.Britta Siegmund has served as a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Falk, Galapagos, Janssen, Lilly, Pfizer, PredictImmune, and Takeda; and served as a speaker for AbbVie, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen,Pfizer, and Takeda.Phillip Levine, Jasmina Kalabic,Ezequiel Neimark, Kori Wallace, Su Chen, and Rachel Duan are AbbVie employees and may own AbbVie stock and/or options.Alessandro Armuzzi has received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, and Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi Tanabe, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda and Tigenix; and research grants from Biogen, MSD, Pfizer, and Takeda.Luc Biedermann has received lecture and consulting fees from Takeda, Sanofi, Abbvie, Falk, BMS, Pfizer and is on advisory boards for Abbvie, Amgen, BMS, Falk, Janssen, Pfizer, Takeda, Sanofi.Edward V. Loftus Jr. has received consulting fees from AbbVie, Alvotech, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene Corporation, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Iterative Scopes, Janssen, Morphic Therapeutic, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Sun Pharma, Surrozen, Takeda, and UCB; receives research support from AbbVie, Bristol Myers Squibb, Celgene Corporation, Genentech, Gilead Sciences, Gossamer Bio, Janssen, Pfizer, Receptos, Takeda, Theravance, and UCB; and is a shareholder of Exact Sciences.Gil Y. Melmed is a consultant for AbbVie, Arena, BI, BMS, Ferring, Fresenius Kalbi, Genentech, Gilead, Lilly, Janssen, Pfizer, Prometheus Labs, Samsung Bioepis, Takeda, and Techlab. He has received research grants from Pfizer.Stefan Schreiber has received consulting fees from AbbVie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Falk Pharma, Ferring, Galapagos/Gilead, Genentech/Roche, GlaxoSmithKline, IMAB Biophatrma, Lilly, MSD, Pfizer, Shire, HIKMA, and Takeda.Funding: AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Acknowledgements: AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial. Paulette Krishack, PhD of AbbVie Inc., provided medical writing assistance for the development of this publication.

Introduction

Interleukin (IL)-23 is a key driver in the pathogenesis of Crohn’s disease (CD). IL-23 is a heterodimer, consisting of p19 and p40 subunits encoded by IL-23A and -23R, respectively. Signaling through the IL-23 receptor complex leads to the transcription of effector cytokine genes, including IL-17A, -17F and -22. Risankizumab (RZB), a monoclonal antibody with specificity for IL-23p19 has demonstrated safety and efficacy for the treatment of CD.^1,2 Here we investigate if baseline (BL) IL-23 pathway gene expression (IL-17A, -17F, -22, -23R, and -23A) in CD patients (pts) is associated with clinical remission and endoscopic response at week (wk) 12 of induction in patients treated with RZB (see Table footnote for endpoint definitions).

Aims & Methods

RNA-sequencing was performed to examine IL-23 pathway gene expression at BL in intestinal biopsy samples (n=280) obtained from pts (n=160) in the 600 mg intravenous (IV) RZB arms of the ADVANCE and MOTIVATE induction studies.¹ Biopsies were taken from the site of active disease (colon [n=146] and/or ileum [n=134]). A linear model based differential expression was conducted between response and non-response using the co-primary endpoints of SF/APS clinical remission and endoscopic response at induction wk 12. Data were normalized using trimmed mean of M-values and log2 counts per million. P-values were adjusted using Benjamini-Hochberg method of multiple testing correction. Comparisons were performed between endoscopic responders or clinical remitters (R) and endoscopic non-responders or clinical non-remitters (NR) in all pts. Analyses were stratified by disease location and/or prior biologic response status.

Results

In the total cohort, IL-23A gene expression was higher at BL in clinical R versus (vs) NR (p=0.03) (see Table for results). However, this difference was only significant in patients with prior bio-failure (p=0.03). Additionally, no difference was observed in IL-23 pathway gene expression between endoscopic R vs NR. When stratifying by disease location, higher BL expression of IL-17A, -17F, -22 and -23A were observed in patients with colonic disease in clinical R vs NR with (p<0.05). This difference was observed in both bio-failure and non-bio-failure patients (p<0.05). No difference was observed between endoscopic R vs NR. In pts with ileal disease, no differences in IL-23 pathway gene expression were observed between clinical R versus NR. Higher BL expression of IL-17A and -17F, and lower BL expression of IL-23R, were demonstrated in endoscopic R vs NR at wk 12 (p<0.05). However this difference was only significant in bio-failure patients.

Conclusion

Endpoint	Patient Subgr​oups​​​​​	Baseline Gene Expression NR vs R Adjusted P-value (p<0.05 denoted in bold)
		IL-17A	IL-17F	IL-22	IL-23R	IL-23A
Clinical Remission at Week 12a	All Patients N=160 (62 R, 98 NR) Colonic Disease N=146 (56 R, 90 NR) Ileal Disease N=134 (47 R, 87 NR) Prior Bio-Failure N=113 (37 R, 76 NR) Without Prior Bio-Failure N=47 (25 R, 22 NR) Colonic Disease + Prior Bio-Failure N=101 (33 R, 68 NR) Colonic Disease + Without Prior Bio-Failure N=45 (23 R, 22 NR) Ileal Disease + Prior Bio-Failure N=94 (26 R, 68 NR) Ileal Disease + Without Prior Bio-Failure N=40 (21 R, 19 NR)	0.40 0.04 0.21 0.11 0.79 0.048 0.51 0.99 0.26	0.5 0.04 0.94 0.10 0.82 0.06 0.50 0.70 0.73	0.17 0.03 0.78 0.26 0.30 0.04 0.41 0.68 0.52	0.95 0.84 0.65 0.23 0.30 0.25 0.45 0.77 0.44	0.03 0.002 0.92 0.03 0.73 0.005 0.44 0.71 0.65
Endoscopic Response At Week 12b	All Patients N=160 (69 R, 91 NR) Colonic Disease N=146 (37 R, 109 NR) Ileal Disease N=134 (35 R, 99 NR) Prior Bio-Failure N=113 (23 R, 90 NR) Without Prior Bio-Failure N=47 (19 R, 28 NR) Colonic Disease + Prior Bio-Failure N=101 (20 R, 81 NR) Colonic Disease + Without Prior Bio-Failure N=45 (17 R, 28 NR) Ileal Disease + Prior Bio-Failure N=94 (18 R, 76 NR) Ileal Disease + Without Prior Bio-Failure, N=40 (17 R, 23 NR)	0.83 0.08 0.01 0.77 0.65 0.10 0.57 0.049 0.19	0.45 0.44 0.049 0.35 0.98 0.49 0.85 0.02 0.9	0.44 0.06 0.42 0.48 0.53 0.09 0.43 0.49 0.90	0.44 0.06 0.42 0.48 0.53 0.09 0.43 0.49 0.90	0.79 0.07 0.10 0.84 1.00 0.09 0.71 0.14 0.63
aAverage daily SF ≤ 2.8 and not worse than BL AND average daily AP score ≤ 1 and not worse than BL; bDecrease in SES-CD > 50% from BL (or for subjects with isolated ileal disease and a BL SES-CD of 4, at least a 2 point reduction from BL), as scored by central reviewer

Minimal differences in BL expression of IL-23 pathway genes were detected in the total cohort between clinical R vs NR and endoscopic R vs NR. Significant differences in BL expression of several IL-23 pathway genes were identified between clinical R and NR in pts with colonic disease. Shared and unique IL-23 pathway genes were significantly altered in pts with ileal disease between endoscopic R vs NR. However, these differences are unlikely to be clinically meaningful or predictive of response to RZB.

References

1. D’Haens G, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. The Lancet. 2022 May;399(10340):2015–30.
2. Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. The Lancet. 2022 May;399(10340):2031–46.

Disclosure

James Lindsay: Consultant and an advisory board participant for AbbVie, Atlantic Healthcare, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Napp, Pfizer, Shire, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Napp, Norgine, Pfizer, Shire, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, Shire and Takeda.
Bram Verstockt: Research support from AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares and Takeda. -Speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion and Viatris. Consultancy fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepont, Mylan, Inotrem, Ipsos, Janssen, Pfizer, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris.
Jean Frederic Colombel: Research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi,Takeda, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development
Valerie Pivorunas, Naim Al Mahi, Nizar Smaoui, F. Stephen Laroux, Kristina Kligys Kori Wallace, and Heath Guay are AbbVie employees and may own AbbVie stock and/or options.

Introduction

Given the natural history of Crohn’s disease (CD), the beneficial effects of treatments may wane over time and result in loss of response. Treatment escalation may aid in re-capturing clinical benefit and improving markers of inflammation. Upadacitinib (UPA) is an oral reversible Janus kinase inhibitor that demonstrated efficacy compared with placebo in 2 phase 3 induction studies and 1 maintenance study, U‑ENDURE, in CD^1-3 and is approved for patients with moderately to severely active CD.⁴ In this post hoc analysis, we evaluated the effect of UPA 30 mg therapy among patients who experienced loss of response to UPA 15 mg maintenance treatment or upon treatment withdrawal.

Aims & Methods

Patients who achieved clinical response (≥ 30% decrease in average daily very soft/liquid stool frequency [SF] and/or abdominal pain score [APS], neither worse than baseline) to 12 weeks of UPA 45 mg once daily (QD) induction therapy were re-randomized to receive UPA 30 mg, UPA 15 mg, or placebo QD in U‑ENDURE (NCT03345823). Beginning at week 4, patients who experienced loss of response and required medical treatment could receive open‑label (OL) UPA 30 mg QD. Loss of response was defined as having clinical symptoms (average daily very soft/liquid SF ≥ 4.0 and/or average daily APS ≥ 2.0) plus an objective marker of inflammation (protocol-specified criteria for high‑sensitivity C-reactive protein [hsCRP], fecal calprotectin [FCP], or Simple Endoscopic Score for CD). Outcomes were assessed at 12 and 24 weeks after initiation of OL UPA 30 mg QD therapy and included clinical remission and clinical response (both per CD Activity Index [CDAI] and SF/APS), enhanced clinical response, and FCP and hsCRP levels. Safety was also assessed. Analyses were based on as observed data without imputation.

Results

Patients who received OL UPA 30 mg QD therapy had, at baseline, a mean CD duration of 10 years, mean CDAI of 304, median hsCRP of 14.3 mg/L, and median FCP of 1550 µg/g; 83.5% had prior biologic failure. At 12 weeks after initiation of OL UPA 30 mg QD, regardless of group during blinded maintenance, 84.4%–87.6% of patients achieved SF/APS clinical response, 77.2%–78.9% achieved enhanced clinical response, 63.3%–71.3% achieved CDAI clinical response, and 46.7%–53.8% achieved SF/APS or CDAI clinical remission (Table). Reponses were sustained through 24 weeks. Median hsCRP and FCP levels decreased after initiation of OL UPA 30 mg QD therapy. Adverse event rates in either group were consistent with those in the overall population. One major adjudicated cardiovascular event in the placebo group and 2 events of non-melanoma skin cancer in the UPA 15-mg group were reported after receiving UPA 30 mg.

Table. Outcomes After Initiation of Open-Label Upadacitinib 30 mg Rescue Therapy
Outcome	Dose Escalation After Loss of Response to UPA 15 mg		Treatment Re-initiation After Loss of Response with PBO Withdrawal
	12 weeks	24 weeks	12 weeks	24 weeks
SF/APS	n = 90	n = 67	n = 145	n = 114
SF/APS clinical responsea Enhanced clinical responseb SF/APS clinical remissionc	76 (84.4) (77.0,91.9) 71 (78.9) (70.5,87.3) 43 (47.8) (37.5,58.1)	60 (89.6) (82.2,96.9) 59 (88.1) (80.3,95.8) 39 (58.2) (46.4,70.0)	127 (87.6) (82.2,93.0) 112 (77.2) (70.4,84.1) 77 (53.1) (45.0,61.2)	103 (90.4) (84.9,95.8) 95 (83.3) (76.5,90.2) 63 (55.3) (46.1,64.4)
CDAI	n = 90	n = 65	n = 143	n = 111
CDAI clinical responsed CDAI clinical remissione	57 (63.3) (53.4,73.3) 42 (46.7) (36.4,57.0)	46 (70.8) (59.7,81.8) 41 (63.1) (51.3,74.8)	102 (71.3) (63.9,78.7) 77 (53.8) (45.7,62.0)	81 (73.0) (64.7,81.2) 62 (55.9) (46.6,65.1)
hsCRP, mg/dL, median (range)	n = 87 4.4 (0.2,75.3)	n = 69 7.0 (0.2,116.0)	n = 147 3.7 (0.2,176.0)	n = 117 3.0 (0.2,75.4)
FCP, µg/g, median (range)	n = 79 715 (30,10901)	n = 55 655 (30,12425)	n = 143 416 (30,11235)	n = 107 356 (30,24853)
APS, abdominal pain score; CDAI, Crohn’s Disease Activity Index; FCP, fecal calprotectin; hsCRP, high-sensitivity C‑reactive protein; PBO, placebo; SF, stool frequency; UPA, upadacitinib. Unless otherwise noted, all results are presented as n (%) (95% CI). a≥ 30% decrease in average daily very soft or liquid SF and/or ≥ 30% decrease in average daily APS and both not greater than baseline. b≥ 60% decrease in average daily very soft or liquid SF and/or ≥ 35% decrease in average daily APS from baseline and both not greater than baseline, or clinical remission per SF/APS. cAverage daily very soft or liquid SF ≤ 2.8 and average daily APS ≤ 1.0 and both not greater than baseline. dDecrease of ≥ 100 points in CDAI from baseline. eCDAI < 150.

Conclusion

Among patients with CD who responded to UPA 45 mg induction therapy and subsequently lost response during maintenance when randomized to placebo or UPA 15 mg QD, most regained clinical response and many achieved clinical remission 12 weeks after initiating UPA 30 mg QD therapy. These improvements were sustained through 24 weeks. No new safety signals were observed.

References

1. Colombel JF, et al. Gastroenterology. 2022;162:S1394.
2. Loftus EV Jr. United European Gastroenterol J. 2022;10;103–104.
3. Panés J, et al. Am J Gastroenterol. 2022;117:S10.
4. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.

Disclosure

RP has received consultancy and/or speaking honoraria from Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead, GSK, JAMP Bio, Janssen, Lilly, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus, Protagonist, Roche, Sandoz, Satisfai Health, Shire, Sublimity, Takeda, Theravance, Trellus, Viatris, and Ventyx, and has received research funding from Abbvie, Janssen, Pfizer, and Takeda.
JOL has received consulting and/or speaker fees from AbbVie, Bristol-Myers Squibb, Celgene, Celltrion, Ferring, Galapagos, Gilead, GSK, Janssen, Lilly, Napp, Pfizer, Shire, Takeda, and Vifor Pharma; and investigator-led research grants from AbbVie, Gilead, Pfizer, Shire, and Takeda.
JP has received financial support for research from AbbVie and Pfizer; consultancy fees/honorarium from AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Robarts, Sanofi, Takeda, Theravance, and Wasserman; reports payment for lectures, including service on speaker bureaus, from Abbott, Ferring, Janssen, Pfizer and Takeda; and reports payment for development of educational presentations from Abbott, Janssen, Pfizer, Roche and Takeda.
PS has received honoraria for consulting and/or speaking activities from AbbVie, Ferring, Janssen, Lilly, Roche, Pfizer, and Takeda. He has served as an investigator for clinical trials sponsored by Abbvie, Gilead, Janssen, Pfizer, and Takeda.
MNR has been a principal investigator for studies sponsored by AbbVie.
MDM-A has received consulting and/or speaker fees from AbbVie, Galapagos, Janssen, Pfizer, Takeda, and Tillotts, and has received research funding from AbbVie, Janssen, and Pfizer.
FB has served as an investigator for clinical trials sponsored by AbbVie and Janssen.
APL, ED, SF, SA, and TF are employees or contractors of AbbVie, and may own AbbVie stock and/or stock options.
GD'H has received honoraria for consulting and/or speaking activities from AbbVie, Alimentiv, Boehringer Ingelheim, Celltrion, Ferring, Galapagos, GSK, Gossamer Bio, Janssen, Lilly, Pfizer, Progenity, Takeda, and Tillotts.
Funding
AbbVie Inc. funded this study 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 Lisa M Pitchford, PhD, of JB Ashtin, and funded by AbbVie.

Introduction

Treatment goals in ulcerative colitis (UC) include controlling inflammation, reducing symptoms, and achieving normalization of quality of life and mucosal healing (MH). Results from Phase 3 induction and maintenance trials (U‑ACHIEVE [NCT02819635] and U-ACCOMPLISH [NCT03653026]) showed rapid relief of UC symptoms (abdominal pain, bowel urgency, stool frequency, rectal bleeding), normalization of fatigue, and MH with upadacitinib (UPA) treatment. Many patients in the program had been exposed to multiple biologics prior to entry and there is a need to understand UPA treatment benefits patients based on disease severity, disease duration, and number of prior biologics used.

Aims & Methods

Patients achieving a clinical response after 8-week induction treatment with UPA 45 mg QD were enrolled in the maintenance trial and re-randomized 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or placebo (PBO) QD. The proportion of patients achieving efficacy outcomes were compared by disease severity (moderate vs severe based on adapted Mayo score), disease duration (by year quartiles), and prior biologic use (0, 1, or 2+) at induction week 8 and maintenance week 52. Outcomes included MH, defined as endoscopic score of 0 and Geboes histologic score <2.0, and complete symptom resolution with fatigue normalization (CSR-FN), defined as remission per partial adapted Mayo score (i.e., stool frequency subscore ≤1 and rectal bleeding subscore of 0), no bowel urgency, no abdominal pain and FACIT-Fatigue score ≥40.1.

Results

More biologic-naïve patients achieved MH normalization than biologic-experienced patients (Table 1). At week 8, 16.5% of biologic-naïve patients achieved MH with UPA 45 mg compared to 6.9%-9.1% of patients with prior experience of 1 or 2+ biologics. After 52 weeks of maintenance, 27.0% (UPA 30 mg) and 21.2% (UPA 15 mg) of biologic-naïve patients achieved MH at maintenance week 52, compared to 16.9%-18.8% (UPA 30 mg) and 12.2%-22.3% (UPA 15 mg) of biologic-experienced patients. Comparable rates of MH were observed regardless of disease severity and disease duration. Comparable rates of CSR-NF were observed regardless of disease severity, disease duration and prior biologic use. UPA 30 mg showed numerically higher efficacy rates vs UPA 15 mg at maintenance week 52.

Proportion of Patients Who Achieve Mucosal Healing and Complete Symptom Resolution with Fatigue Normalization with UPA treatment at Weeks 8 and 52: NRI-C
	Mucosal Healing					Complete Symptom Resolution and Fatigue Normalization
	Induction (Week 8)		Maintenance (Week 52)a			Induction (Week 8)		Maintenance (Week 52)a
n/N (%)	PBO N=328	UPA 45 mg N=660	PBO N=223	UPA 15 mg N=225	UPA 30 mg N=233	PBO N=328	UPA 45 mg N=660	PBO N=223	UPA 15 mg N=225	UPA 30 mg N=233
Moderate Severe	3/197 (1.5) 2/131 (1.5)	50/402 (12.5)* 30/258 (11.6)*	4/131 (3.1) 7/92 (7.8)	32/140 (23.0)* 10/85 (11.8)	33/139 (23.5)* 20/94 (21.1)*	15/197 (7.6) 7/131 (5.3)	95/402 (23.5)* 60/258 (23.3)*	15/131 (11.5) 11/92 (12.1)	35/140 (25.0)* 18/85 (21.2)	55/139 (39.7)* 35/94 (37.1)*
Disease Durationab Quartile 1 Quartile 2 Quartile 3 Quartile 4	1/83 (1.2) 2/91 (2.2) 2/70 (2.9) 0/84 (0)	29/164 (17.8)* 17/156 (10.9)* 17/177 (9.6) 17/163 (10.4)*	5/55 (9.1) 0/62 (0.3) 3/53 (5.7) 3/53 (5.8)	12/55 (21.8) 13/57 (23.1)* 8/54 (14.9) 9/59 (15.3)	12/64 (19.4) 19/57 (33.7)* 13/58 (22.9)* 8/54 (14.2)	6/83 (7.2) 6/91 (6.6) 7/70 (10.0) 3/84 (3.6)	36/164 (21.9)* 30/156 (19.2)* 50/177 (28.3)* 39/163 (23.7)*	5/55 (9.1) 5/62 (8.2) 9/53 (17.0) 7/53 (13.2)	15/55 (27.3)* 12/57 (21.1)* 11/54 (20.4) 15/59 (25.4)	22/64 (34.7)* 28/57 (49.1)* 20/58 (34.5)* 20/54 (36.7)*
Prior biologics 0 1 2+	3/153 (2.0) 2/69 (2.9) 0/106 (0)	51/311 (16.5)* 9/130 (6.9) 20/219 (9.1)*	8/102 (7.9) 0/49 (0.2) 3/72 (4.3)	24/114 (21.2)* 10/45 (22.3)* 8/66 (12.2)	32/117 (27.0)* 7/44 (16.9)* 14/72 (18.8)*	16/153 (10.5) 2/69 (2.9) 4/106 (3.8)	80/311 (25.7)* 40/130 (30.5)* 35/219 (16.0)*	17/102 (16.7) 3/49 (6.1) 6/72 (8.5)	31/114 (27.2) 13/45 (28.9)* 9/66 (13.6)	48/117 (40.8)* 13/44 (30.2)* 29/72 (40.3)*
*p≤0.05 for UPA vs PBO. NRI-C is non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19. Mucosal healing was defined as endoscopic score of 0 and Geboes histologic score <2.0. Complete symptom resolution with fatigue normalization (CSR-FN), defined as remission per partial adapted Mayo score (i.e., stool frequency subscore ≤1 and rectal bleeding subscore of 0), no bowel urgency, no abdominal pain and FACIT-Fatigue score ≥40.1. aThe maintenance study population comprises patients who achieved clinical response after UPA 45 mg QD 8-week induction treatment and were enrolled in the 52-week maintenance treatment period. bQuartiles for disease duration are Q1: (0, 2.7], Q2: (2.7, 5.8], Q3: (5.8, 11.2] and Q4: >11.2 years for induction, and Q1: (0,2.8], Q2: (2.8,6.1], Q3: (6.1,11.7] and Q4: >11.7 years for maintenance.

Conclusion

UPA demonstrated benefits in MH and CSR-NF regardless of disease severity, disease duration, and prior biologic use. Higher rates of MH at the end of induction and maintenance were observed in biologic-naïve vs biologic-experienced patients, suggesting additional benefits from using UPA early in the treatment pathway as a first-line advanced therapy.

Disclosure

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 Joann Hettasch, PhD, of Fishawack Facilitate, Ltd, part of Fishawack Health, and funded by AbbVie.
Disclosures
Edward V. Loftus Jr: served as a consultant for AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota, Iterative Scopes, Janssen, Morphic Therapeutics, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Sun Pharma, Takeda, and UCB; and received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, and UCB.
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.
Gareth Parkes received personal payments/honoraria/speaker fees and/or accepted travel grants or fellowships from AbbVie, Allergan, BMS, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts; and is a Director and Shareholder in Ampersand Health.
Ken Takeuchi has received consulting fees from Thermo Fisher Diagnostics K.K.; and research grants from AbbVie and Takeda; and has served as a speaker for AbbVie, Celltrion Healthcare, EA Pharma, Janssen, Kyorin, Mochida, Takeda, Tanabe Mitsubishi, and Zeria.
Si Xuan, James Crooks, Justin Klaff, and Yuri Sanchez Gonzalez are full-time employees of AbbVie and may hold AbbVie stock and/or stock options.
Silvio Danese has received consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB, and Vifor Pharma.

Introduction

Intravenous infliximab and vedolizumab are used as maintenance therapy for moderate to severe ulcerative colitis and Crohn’s disease. During maintenance therapy these drugs are administrated usually at every 6 to 8 weeks. In Finland, subcutaneous vedolizumab became available 2020 and subcutaneus infliximab 2021, making it possible to switch from infusions to injections. According to previous studies, subcutaneous administration of these drugs is equally effective as intravenous in treatment of inflammatory bowel disease (IBD). It has also been calculated that in most European countries switching from infusions to injections reduces costs.

Aims & Methods

At Hyvinkää hospital, a development project was performed 1.1.-31.12.2022 to switch all IBD patients on intravenous infliximab or vedolizumab therapy to injections. The median intravenous dose of infliximab was 500 mg (300-1000 mg) at a median interval of 8 weeks (6-10 weeks) and the standard dose of intravenous vedolizumab was 300 mg every 8 weeks. Standard doses on infliximab 120 mg and vedolizumab 108 mg every second week were used for subcutaneous therapy. Infliximab and vedolizumab trough levels were measured both during infusions and injections to ensure that the concentrations remained within therapeutic levels. We also wanted to calculate the average yearly drug costs per patient during infusions and injections and the impact on the day hospital burden.

Results

75 patients (mean age 43 years, range 19-76, 44 male, 31 female) switched from infliximab and 21 patients (mean age 52 years, range 21-77, 16 male, 5 female) from vedolizumab infusions to injections. The infliximab concentration was 8,1 ± 4,5 µg/ml during infusions and 14,8 ± 6,6 µg/ml during injections (n = 41), P < 0.001. The vedolizumab concentration was 15,2 ± 7,2 mg/m during infusions and 28,3 ± 14,3 mg/ml during injections (n = 15), P < 0.005. Four patients in the infliximab and two patients in the vedolizumab group interrupted therapy because of relapse or remission. Eleven patients in the infliximab and one in the vedolizumab group were inductions and their trough levels for infusions are not available. Follow-up is still going on and results for all drug concentrations are not yet available. The average yearly cost of infusions and injections per patient were 17556,20 € and 7481,76 € for infliximab (n = 75) and 22777,61 € and 13101,01 € for vedolizumab (n = 21), respectively. The reduction of day hospital visits was 517 in total (on average 6,9 visits per patient). 23 patients (mean age 49 years, range 17-81, 14 male, 9 female, 20 on infliximab and 3 on vedolizumab) wished to continue infusions.

Conclusion

The trough levels of infliximab and vedolizumab are significantly higher during injections than during infusions. Subcutaneous administration reduces costs compared to intravenous administration and considerably reduces the burden of day hospital visits. Further studies are needed to assess separate trough levels for subcutaneous administration of infliximab and vedolizumab and to make recommendations for optimal dosing of these drugs.

Introduction

Upadacitinib (UPA) is an oral, reversible Janus kinase (JAK) inhibitor that recently demonstrated efficacy compared with placebo (PBO) in 2 double-blind, multicenter induction studies, U-EXCEED (NCT03345836) and U-EXCEL (NCT01205776), and in a pre-specified primary analysis of 502 patients in the phase 3 maintenance study U-ENDURE (NCT03345823).^1-3 UPA is approved for the treatment of moderately to severely active Crohn’s disease (CD).^4,5 The current analysis evaluated the efficacy and safety of UPA in the full intent-to-treat maintenance population of U-ENDURE.

Aims & Methods

After 12 weeks of induction therapy, clinical responders (patients who achieved ≥ 30% decrease in average daily very soft/liquid stool frequency [SF] and/or ≥ 30% decrease in average daily abdominal pain score [APS] and both not worse than baseline) to UPA 45 mg were re‑randomized to 52 weeks of maintenance therapy with UPA 30 mg (UPA30), UPA 15 mg (UPA15), or placebo (PBO) once daily. Efficacy outcomes, including clinical remission per SF/APS, clinical remission per CD Activity Index (CDAI), endoscopic response, maintenance of clinical remission, clinical response per CDAI (CR-100), endoscopic remission, steroid-free clinical remission, and deep remission (clinical remission combined with endoscopic remission) were assessed through 52 weeks. Safety during U-ENDURE was documented. The efficacy analysis included all patients who were randomized and received ≥ 1 dose of study drug in U‑ENDURE.

Results

Among 673 patients included in this analysis (UPA30, n = 229; UPA15, n = 221; PBO, n = 223), all efficacy endpoints were achieved by a greater proportion of patients receiving UPA at either dose vs PBO at week 52 (Table). More patients receiving UPA achieved the co‑primary endpoints of clinical remission (per SF/APS: UPA30, 49.3%; UPA15, 33.9%; PBO, 15.2%; per CDAI: UPA30, 51.5%; UPA15, 36.2%; PBO, 15.2%; P < .0001 for both UPA doses vs PBO) and endoscopic response (UPA30, 40.7%; UPA15, 27.3%; PBO, 7.2%; P < .0001 for both doses vs PBO) over 52 weeks. Rates of any adverse events (AEs), serious AEs, and severe AEs were numerically lower with UPA compared with PBO. The rates of most AEs of special interest were similar between UPA and PBO, with the exception of higher rates of herpes zoster, neutropenia, and creatine phosphokinase elevation in the UPA30 group. Hepatic disorders (mostly transaminase elevations) were reported more frequently with UPA than PBO. One gastrointestinal perforation was reported in each of the three treatment groups. No deaths, active tuberculosis, lymphoma, nonmelanoma skin cancer, major adjudicated cardiovascular events, or venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were reported for any treatment arm.

Table. Achievement of Key Clinical and Endoscopic Outcomes During the Upadacitinib Maintenance Study at Week 52
Patients Achieving Outcome	PBO (n = 223)	UPA 15 mg (n = 221)	Adjusted difference vs PBO, % (95% CI)	UPA 30 mg (n = 229)	Adjusted difference vs PBO, % (95% CI)
Clinical endpoints Clinical remission, % Per CDAIa Per SF/APSb Maintenance of clinical remissionc, (%) Per CDAI Per SF/APS CR-100d, % Corticosteroid-free clinical remission per CDAIe, % Among all patients Among patients taking corticosteroids at induction baseline Corticosteroid-free clinical remission per SF/APSe, % Among all patients Among patients taking corticosteroids at induction baseline	15. 2 15.2 21.2 21.6 17.0 14.8 6.3 15.2 6.3	36.2*** 33.9*** 48.5*** 48.9*** 38.9*** 34.8*** 33.8*** 33.0*** 32.5***	21.9 (14.5–29.3) 19.2 (12.2–26.3) 28.9 (18.8–39.1) 28.2 (18.0–38.3) 22.4 (14.6–30.1) 21.0 (13.7–28.3) 29.2 (18.1–40.3) 18.3 (11.3–25.4) 28.0 (17.0–39.0)	51.5*** 49.3*** 66.7*** 60.7*** 52.8*** 50.7*** 44.7*** 48.0*** 42.4***	36.1 (28.4–43.7) 33.5 (26.0–41.0) 44.6 (34.5–54.8) 38.2 (27.9–48.4) 35.5 (27.7–43.3) 35.7 (28.0–43.3) 37.0 (25.8–48.2) 32.2 (24.7–39.7) 36.7 (25.9–47.5)
Endoscopic endpoints Endoscopic responsef, % Endoscopic remissiong, %	7.2 5.4	27.3*** 18.6***	20.6 (14.1–27.0) 13.7 (8.0–19.5)	40.7*** 30.6***	33.8 (27.1–40.4) 25.2 (18.8–31.6)
Composite endpoints Clinical remission per CDAI and endoscopic remissionh, % Clinical remission per SF/APS and endoscopic remissionh, %	3.6 4.1	15.0*** 14.1***	12.0 (6.8–17.2) 10.3 (5.2–15.5)	26.2*** 25.8***	22.6 (16.6–28.5) 21.4 (15.4–27.5)
APS, abdominal pain score; CDAI, Crohn’s Disease Activity Index; CR-100, clinical response 100; PBO, placebo; SF, stool frequency; UPA, upadacitinib. ***P < .001 vs PBO. aClinical remission per CDAI: CDAI < 150. bClinical remission per SF/APS: average daily very soft or liquid SF ≤ 2.8 and average daily APS ≤ 1.0 and both not greater than baseline. cMaintenance of clinical remission per CDAI or SF/APS: achievement of CDAI or SF/APS clinical remission among patients who had CDAI or SF/APS clinical remission at the end of induction. dCR-100: decrease of ≥ 100 in CDAI from baseline. eCorticosteroid-free clinical remission: Achievement of clinical remission per CDAI or SF/APS without corticosteroid use ≥ 90 days prior to week 52. fEndoscopic response: decrease in Simple Endoscopic Score for CD [SES-CD] > 50% from baseline of the induction study (or for patients with an SES-CD of 4 at baseline of the induction study, at least a 2 point reduction from baseline. gEndoscopic remission: SES-CD ≤ 4 and ≥ 2-point reduction from baseline, and no subscore > 1 in any individual variable.

Conclusion

Both UPA maintenance doses were more efficacious than PBO for achieving clinical and endoscopic endpoints and had a tolerable safety profile with no new safety signals. Response and remission rates were numerically higher for patients receiving UPA30 compared with UPA15. These results are consistent with published data³ and further support the use of UPA as maintenance therapy in this patient population.

References

1. Loftus E, et al. United European Gastroenterol J. 2022;10:OP129.
2. Colombel JF, et al. Gastroenterology. 2022;162:867f.
3. Panés J, et al. Am J Gastroenterol. 2022;117:S10.
4. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
5. Electronic Medicines Compendium. Rinvoq (upadacitinib) 30 mg prolonged-release tablets: summary of product characteristics. Updated March 16, 2023. Accessed March 27, 2023. https://www.medicines.org.uk/emc/product/12830/smpc/

Disclosure

MR has received research support from AbbVie, Janssen, and Takeda and unrestricted educational grants from AbbVie, Janssen, Pfizer, Salix, Shire, Takeda, and UCB; and has served on advisory boards and as a consultant for AbbVie, Allergan, Amgen, Celgene, Janssen, Miraca Labs, Pfizer, Seres, Takeda, and UCB.
SDL has served as a consultant for Cornerstones, Janssen, Lilly, Pfizer, and UCB; and received grant and research support from AbbVie, Arena, Celgene, Janssen, Shield Therapeutics, Takeda, Tetherex, and UCB.
RA has served as a speaker or consultant, or received research grants from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, MSD, Novartis, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda, and Tillotts Pharma.
EB has received speaking honoraria fees from AbbVie, Ferring, Janssen, and Takeda.
CR has received consultancy and/or speaking honoraria fees from AbbVie, Ferring, Galapagos, Janssen, Pfizer, and Takeda.
AAvB has served as a consultant or speaker for AbbVie, Arena, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda, Teva, Tramedico, Vifor, and Dutch Ministry of Health (ZonMW); received research grants from Ferring, Pfizer, and Teva; and has performed as principal investigator in studies sponsored by Abivax, Arena, Celltrion, Janssen, Pfizer, Roche, and Teva.
ED, APL, JL, TF, ZG, VPR, and SIA are employees of AbbVie and may own stock and/or options.
JP has received financial support for research from AbbVie and Pfizer; received lecture fee(s) from AbbVie, Ferring, Janssen, Takeda; and received consultancy fees from AbbVie, Arena Pharmaceuticals, Athos, Boehringer Ingelheim, Celltrion, Ferring, Galapagos, Genentech, GSK, Janssen, Mirum, Morphic, Origo, Pandion, Pfizer, Protagonist, Revolo, Robarts, Roche, Takeda, Theravance, and Wassermann.
Funding
AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of this 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 the authors thank the patients who participated in the study and all study investigators for their contributions. AbbVie funded the research for this study and provided writing support for this abstract. Medical writing assistance, funded by AbbVie, was provided by Spencer Hughes, PhD, of JB Ashtin.