Introduction
The Phase 2 GALAXI 1 study evaluated the efficacy and safety of guselkumab (GUS), a human selective IL-23p19 subunit antagonist, in patients (pts) with moderate to severe Crohn’s disease (CD). Pts were randomized to GUS, ustekinumab (UST), or placebo (PBO) through Week (Wk) 48 without rerandomization after IV induction. Previously, we reported that pts who were in clinical response after IV induction had higher rates of clinical and endoscopic outcomes at Wk48 than the overall study population.1 In this post hoc analysis, we report outcomes for pts who did not achieve Wk12 clinical response based on CD activity index (CDAI) after IV induction.
Aims & Methods
Pts were randomized 1:1:1:1:1 to induction with GUS 200, 600, or 1200mg IV, UST ~6mg/kg IV, or PBO IV. At Wk12 (Wk8 for UST), pts were transitioned to maintenance dosing: GUS 200mg IV→100mg subcutaneous (SC) q8w, GUS 600mg IV→200mg SC q4w, GUS 1200mg IV→200mg SC q4w, UST ~6mg/kg IV→90mg SC q8w, PBO nonresponders→UST ~6mg/kg IV→90mg SC q8w, and PBO responders→PBO SC q4w. Clinical response (all time points) was defined as ≥100-point reduction from baseline in CDAI or CDAI <150. Other endpoints included clinical remission (CDAI <150), pt-reported outcome (PRO)-2 remission (unweighted CDAI components of average daily abdominal pain score ≤1 and average daily stool frequency ≤3, and no worsening from baseline), and endoscopic response (≥50% improvement from baseline in simple endoscopic score [SES]-CD or SES-CD ≤2). The study was not powered to evaluate between-group efficacy differences at Wk48; UST was used for reference.
Results
Table. Efficacy Outcomes Among Patients Not in Clinical Responsea at Week 12
|
|---|
Outcome, %b, c
| Week | Combined Guselkumab (N=63)
| Ustekinumab (N=21)
|
Clinical responsea
| 16 / 20 / 24
| 36.5 / 47.6 / 46.0
| 42.9 / 52.4 / 52.4
|
| 28 / 32 / 36
| 47.6 / 54.0 / 50.8
| 42.9 / 47.6 / 57.1
|
| 40 / 44
| 54.0 / 52.4
| 52.4 / 47.6
|
| 48
| 58.7
| 47.6
|
Clinical remissiond
| 48 | 41.3
| 33.3
|
PRO-2 remissione
| 48 | 42.9
| 23.8
|
Endoscopic responsef
| 48 | 31.7
| 23.8
|
AP=abdominal pain; CD=Crohn’s disease; CDAI=Crohn’s disease activity index; PRO-2=Patient-reported CDAI components of abdominal pain and stool frequency; SES-CD=Simple Endoscopic Score for Crohn’s Disease; SF=stool frequency.
a Clinical response was defined as ≥100-point reduction from baseline in CDAI or CDAI <150.
b Patients who had a prohibited change in concomitant CD medication, a CD-related surgery, or discontinued study agent due to lack of efficacy, or an adverse event of worsening CD prior to the designated analysis timepoint, were considered not to have achieved the endpoint.
c Patients who had insufficient data to calculate the outcome measure at the designated analysis timepoint were considered not to have achieved the endpoint.
d Clinical remission was defined as a CDAI <150.
e PRO-2 remission was defined as unweighted CDAI component of average daily AP pain score ≤1 and the unweighted CDAI component of average daily SF ≤3, and no worsening of AP or SF from baseline.
f Endoscopic response was defined as ≥50% improvement from baseline in SES-CD or SES-CD ≤2.
|
At Wk12, 63/185 (34.1%) GUS pts and 21/63 (33.3%) UST did not achieve CDAI clinical response. Among GUS Wk12 nonresponders, 46.0% were in clinical response by Wk24 (Table). Percentages of Wk12 nonresponders who went on to achieve outcomes at Wk48 in the GUS and UST groups, respectively, were as follows: clinical response, 58.7% and 47.6%; clinical remission, 41.3% and 33.3%; PRO-2 remission, 42.9% and 23.8%; and endoscopic response, 31.7% and 23.8% (Table).
Conclusion
Pts not responding to IV induction with GUS may benefit from continued SC dosing. Among pts who did not achieve clinical response at Wk12, continued treatment with GUS SC resulted in nearly half achieving clinical response at Wk24. At Wk48, a majority achieved clinical response, >40% achieved either clinical remission or PRO-2 remission, and >30% achieved endoscopic response.
References
1. Panés J, et al. UEG Journal 2022; 10 (Suppl 8).
Disclosure
RP reports consulting fees, speaker fees, or research support from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.
AA reports consulting fees from AbbVie, Takeda, Janssen, Bristol Myers Squibb/Celgene, Pfizer, Eli Lilly, Gilead, DiaSorin, and TLL Pharmaceuticals; reports speaker fees from Abbvie, Takeda, Janssen, Bristol Myers Squibb, and Pfizer; has served on advisory boards for Abbvie, Takeda, Janssen, Bristol Myers Squibb, Pfizer, Eli Lilly, and Gilead; has received research/education support from AbbVie, Janssen, Pfizer, Bristol Myers Squibb, and Takeda; and is the co-founder of IBD Horizons.
GRDH served as advisor for Abbvie, Ablynx, Amakem, Amgen, AM Pharma, Avaxia, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, DrFALK Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, Glaxo-Smith Kline, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Prometheus laboratories/Nestle, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor; and has received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts, and Vifor.
LS, NAT, AS, MEF, and ZY are employees of Janssen Research & Development, LLC and own stock/stock options.
EZ reports receiving research support and consulting fees from Janssen, AbbVie, Takeda, Neopharm, Celgene, and Pfizer.
SD reports receiving consulting fees from Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion Healthcare, Ferring, Gilead Sciences, Hospira, Inc., Janssen Research & Development, LLC, Johnson & Johnson Health Care Systems, Inc., Pfizer, Sandoz, UCB, and Vifor International Inc.
TH has performed joint research with Alfresa Pharma Co. Ltd., and EA Pharma Co. Ltd.; has received grant support from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Daiichi-Sankyo, Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., and JIMRO Co. Ltd; has received consulting fees from EA Pharma Co. Ltd., AbbVie GK, Celgene K.K., Janssen Pharmaceutical K.K., Pfizer Inc., and Nichi-Iko Pharmaceutical Co., Ltd; and has received lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Pfizer Inc.
