Introduction
Guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, has demonstrated efficacy in patients (pts) with ulcerative colitis (UC) treated with intravenous or subcutaneous (SC) induction. Here, we report efficacy and safety results of SC maintenance GUS through week (W)96 in ASTRO, a randomized, double-blind, placebo-controlled, treat-through phase 3 trial in pts with moderately to severely active UC.
Aims & Methods
Pts were randomized at W0 to receive GUS 400 mg SC q4w (x3)→GUS 100 mg SC q8w, GUS 400 mg SC q4w (x3)→GUS 200 mg SC q4W, or placebo SC. Pts who benefited from treatment (trt) at W24 were eligible for the study extension (SE) with trt to be continued through W248. Upon study unblinding after W48, placebo pts who were not rescued with GUS discontinued trt; therefore, placebo efficacy data are not reported. Symptomatic remission, UC PRO/SS assessments of bowel urgency and abdominal pain, and levels of inflammatory biomarkers C-reactive protein (CRP) and fecal calprotectin were assessed through W96 in pts who continued trt beyond W48. “As observed” and modified nonresponder imputation analyses are reported. A cumulative safety analysis through W96 included all treated pts at W0. No endoscopic or histologic outcomes were assessed at W96.
Results
A total of 235 pts who were randomized to GUS continued trt after W48. At W96, the proportion of pts in symptomatic remission was 81.9% and 82.8% (observed) and 64.2% and 71.3% (modified NRI) in the GUS 100 mg SC q8w and GUS 200 mg SC q4w trt arms, respectively (Table). A similar pattern was reported in the advanced therapy pt subgroups (Table). The majority of pts (observed) reported no bowel urgency (75.3%, 76.5%) and no abdominal pain (72.0%, 79.6%), and median CRP (1.10 mg/L, 1.50 mg/L) and fecal calprotectin (142 mg/kg, 136 mg/kg) levels at W96 were similar among pts in the GUS 100 mg SC q8w and GUS 200 mg SC q4w arms, respectively (Table). Treatment-emergent events per 100 PY through W96 following randomized GUS 100 mg SC q8w and GUS 200 mg SC q4w vs placebo SC trts were: AEs 266.34 and 274.05 vs 289.45, serious AEs 5.67 and 6.70 vs 30.71, AEs leading to discontinuation of drug 3.05 and 3.57 vs 14.89, and serious infections 0.87 and 1.34 vs 2.79, respectively.
Table. Symptom outcomes at W96 among patients who were randomized to GUS continued treatment after W48
| Guselkumaba |
| 400 mg SC q4w (x3)b → 100 mg SC q8w | 400 mg SC q4w (x3)b → 200 mg q4w |
Endpoint
| Observed
| Modified NRIc
| Observed
| Modified NRIc
|
Symptomatic remissiond
|
|
|
|
|
All pts
| 81.9% (77/94)
| 64.2% (77/120)
| 82.8% (82/99)
| 71.3% (82/115)
|
| ADT-IR | 71.4% (25/35)
| 53.2% (25/47)
| 70.6% (24/34)
| 53.3% (24/45)
|
| ADT-Naïve | 88.1% (52/59)
| 72.2% (52/72)
| 90.6% (58/64)
| 84.1% (58/69)
|
No bowel urgencye
| 75.3% (70/93)
| 58.3% (70/120)
| 76.5% (75/98)
| 65.2% (75/115)
|
No abdominal painf
| 72.0% (67/93)
| 55.8% (67/120)
| 79.6% (78/98)
| 67.8% (78/115)
|
Data are presented as % patients (n/N).
ADT, advanced therapy; ADT-IR, inadequate response to or intolerance of advanced therapy (TNFα antagonists, vedolizumab, ozanimod, or approved JAK inhibitors); AE, adverse event; NRI, nonresponder imputation; Q, question; Q4W, every 4 weeks; Q8W, every 8 weeks; SC, subcutaneous; UC, ulcerative colitis; UC-PRO/SS, Ulcerative Colitis-Patient-reported Outcome/Signs and Symptoms, W, week.
aAll randomized patients who received at least one dose of guselkumab (including a partial dose) at or after W48.
bGuselkumab 400 mg SC q4w at W0, W4, and W8.
cPatients who, prior to W96, had an ostomy or colectomy or discontinued study agent due to lack of efficacy or an AE of worsening of UC were considered not to have achieved any of the binary efficacy endpoints at W96. For patients who discontinued study agent due to COVID-19-related reasons (excluding COVID-19 infection) or regional crisis, their observed values were used, if available. Patients who discontinued study agent prior to W96 due to other reasons were considered not to have achieved any of the binary efficacy endpoints at W96. Patients with insufficient data to calculate a binary efficacy endpoint at W96 were considered not to have achieved the endpoint at W96.
dSymptomatic remission is defined as a stool frequency subscore of 0 or 1 and no increase from baseline, and a rectal bleeding subscore of 0.
eNo bowel urgency is defined as a rounded daily average (within 1 week) score of 0 in question (Q) 7 of the UC-PRO/SS.
Q7: In the past 24 hours, did you feel the need to have a bowel movement right away?
fNo abdominal pain is defined as a rounded daily average (within 1 week) score of 0 in question (Q) 8 of the UC-PRO/SS.
Q8: In the past 24 hours, did you feel pain in your belly? |
Conclusion
SC maintenance therapy following induction therapy demonstrated symptomatic and inflammatory biomarker improvements through 2 years of trt. The safety data was consistent with the established safety profile of GUS.
Disclosure
ML reports research support from Lilly, Pfizer, and Takeda; consulting for AbbVie, Bristol Myers Squibb, Intercept, Janssen (Johnson & Johnson), Lilly, Pfizer, Prometheus, Roivant, Takeda, and Target RWE.
LPB reports grants or contracts from Celltrion, Fresenius Kabi, Medac, MSD, and Takeda; consulting and/or payment or honoraria and/or data safety monitoring board or advisory board participation for AbbVie, Abivax, Adacyte, Alfasigma, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Kern Pharma, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, and Ysopia; and meeting attendance/travel support from AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, and Tillots.
TH reports research grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; and lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
JRA reports grant support from Janssen, Merck, and Pfizer; consultancy fees from AbbVie, Adiso, Bristol Myers Squibb, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer, Roivant, Celltrion, TrexBio, Shattuck Labs and Seres Therapeutics; payments for speaking from AbbVie, Bristol Myers Squibb, and Janssen; and is a steering committee member and investigator for Janssen.
YA, TB, KH, CH, HZ, and YM are employees of and may own stock in Johnson & Johnson.
DTR reports consulting and/or speaker fees and/or advisory board participation for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen (Johnson & Johnson), Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; and membership on the Board of Directors of Cornerstones Health, Inc. and on the Crohn’s & Colitis Foundation’s Board of Trustees.
SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.