Subcutaneous Guselkumab Proves Efficacious for IBD
BERLIN — Induction therapy with subcutaneous guselkumab demonstrated significant efficacy in patients with moderately to severely active ulcerative colitis (UC), according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study. Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC. “The flexibility of a fully
BERLIN — Induction therapy with subcutaneous guselkumab demonstrated significant efficacy in patients with moderately to severely active ulcerative colitis (UC), according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the Inflammatory Bowel Disease (IBD) Unit at University Hospital of Nancy, Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2src25 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)-23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 4srcsrc mg subcutaneous guselkumab at weeks src, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 2srcsrc mg subcutaneous guselkumab at week 12 and then every 4 weeks or 1srcsrc mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 6src% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P <.srcsrc1).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P <.srcsrc1). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P=.srcsrc5).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 3src%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 3src% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of src or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P <.srcsrc1).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group compared with 41.8% in the placebo group (P <.srcsrc1). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group compared with 25.src% in the placebo group (P <.srcsrc1).
Turning to endoscopic improvement (ie, an endoscopic subscore of src or 1 with no friability), 37.3% of those in the guselkumab group overall compared with 12.9% of those in the placebo group achieved this endpoint (P <.srcsrc1).
“This is a treatment effect of over 2src%,” said Peyrin-Biroulet. “We know that when it is over 2src%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2src25 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (4srcsrc mg every 4 weeks followed by 1srcsrc mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, England, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting last October.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumabcompared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (2srcsrc mg) and 6src.src% (1srcsrc mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 2srcsrc-mg maintenance dose and in 44.3% on the 1srcsrc-mg maintenance dose compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 2srcsrc-mg guselkumab group and in 3src.4% in the 1srcsrc-mg guselkumab group compared with 6.src% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said.
Furthermore, data from the ASTRO study demonstrated similar data in the UC population, she added.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 2srcsrc mg subcutaneous guselkumab every 4 weeks or 1srcsrc mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” co-moderator, Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, told Medscape Medical News.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants from Takeda, Fresenius Kabi, Celltrion, Medac, and MSD; personal fees from AbbVie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Eli 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 other/support travel from AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Eli Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots.
Hart declared receiving grants from Takeda and personal fees from AbbVie, Amgen, Arena, AZ, Falk, Celltrion, Eli Lilly, Ferring, Genentech/Roche, GSK, Pfizer, Takeda, Napp, Pharmacosmos, Janssen (J&J), Bristol Myers Squibb, Gilead, and Galapagos.
Bamias declared receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as an advisor/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, J&J, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.
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