New efficacy and safety data from the Phase 3 QUASAR Induction Study evaluating the investigational use of TREMFYA® (guselkumab) in adults with moderately to severely active ulcerative colitis (UC) who had an inadequate response or intolerance to conventionalb and/or advanced therapies were released by Janssen Pharmaceutical Companies of Johnson & Johnson today. According to the results, improvements in symptomatic and histo-endoscopic outcome markers are both statistically significant and clinically meaningful.
The safety statistics were similarly in line with TREMFYA’s established safety profile when used for approved indications.1 These findings make up one of Janssen’s 17 oral and poster presentations at the conference, which will be held in Chicago, Illinois, from May 6–9, 2023. They were approved as a late-breaking oral presentation to the Digestive Disease Week® (DDW) Annual Meeting.
“Many people living with ulcerative colitis, especially those who have had inadequate response to other treatments, live with uncertainty and continue to experience debilitating symptoms,” said study author Jessica R. Allegretti, M.D., M.P.H., Medical Director, Crohn’s and Colitis Center at the Brigham and Women’s Hospital in Boston, Massachusetts, USA.
“Researchers are continuing to look into therapeutic options that may be able to provide relief for people at all stages of the disease, and these Phase 3 data represent an important step in the advancement of a new treatment for moderately to severely active ulcerative colitis,” according to the authors.
Results of the QUASAR Phase 3 Induction Study
Results from 701 patients who were randomized 3:2 to receive TREMFYA 200 mg intravenously (IV) or a placebo at weeks 0, 4, and 8 and followed up to week 12 show:
At Week 12, the study’s primary endpoint, a considerably higher percentage of patients receiving TREMFYA than placebo (22.6 percent versus 7.9 percent, p0.001, f=14.9 percent) did so.
At Week 4, 22.6 percent of TREMFYA patients and 12.9 percent of placebo patients, respectively, had achieved symptomatic remission (p0.001, 9.9 percent). At Week 12, 49.9% of patients had symptomatic remission compared to 20.7 percent of placebo recipients (p0.001, equals 29.4%);1
At Week 12, a higher percentage of TREMFYA-treated patients than placebo accomplished:
Clinical response (61.5% versus 27.9% for the placebo; p=0.001, equals 33.8%)1
Endoscopic improvement (268.8% versus 11.10% placebo [p0.001, =16.08%])1 Histo-endoscopic mucosal improvementk (23.5% versus 7.5% placebo [p0.001, =16.2%])1 Endoscopic normalization (15.0% versus 5.0% placebo; nominal p=0.001, =10.1%)Patients receiving TREMFYA typically had adverse events (AEs) at a rate similar to that of placebo.
Patients receiving TREMFYA experienced numerically fewer major adverse events (AEs) (2.9 percent TREMFYA versus 7.1 percent placebo) and AEs that resulted in discontinuation (1.7 percent TREMFYA against 3.9 percent placebo) than those receiving placebo1.
Overall, safety data through Week 12 were in line with TREMFYA’s approved indications’ known safety profile1.
According to Kavitha Goyal, M.D., Head of Global Medical Affairs, Gastroenterology, Janssen Global Services, LLC, “Results from the QUASAR study offer insights into the potential utility of TREMFYA for people living with this lifelong chronic condition and reinforce the known safety profile of TREMFYA observed in approved indications.” “Janssen continues to investigate IL-23 pathway science with TREMFYA for the treatment of complex immune-mediated diseases like ulcerative colitis, so that healthcare providers can have a range of treatment options that best fit patients’ needs and can bring them closer to the goal of remission.”
TREMFYA is the subject of ongoing Phase 3 studies for the treatment of individuals with inflammatory bowel illness, including Crohn’s disease (NCT03466411, NCT05197049) and ulcerative colitis (NCT04033445, NCT05528510).2,3,4,5
In the United States, TREMFYA is not authorized for the treatment of people with UC
A. The use of thiopurines or corticosteroids1
b. the use of tumor necrosis factor alpha antagonists, such as vedolizumab or tofacitinib1
c. the baseline modified Mayo score of 5 to 9, which includes a rectal bleeding subscore of 1 and an endoscopy subscore of 2 evaluated during central review of video endoscopy1
D. As a paid consultant for Janssen, Dr. Allegretti. For any work with the media, Dr. Allegretti has not received any payment.
E. The average age was 40.5 years; 43.1 percent of the population was female; the average UC duration was 7.5 years; the average modified Mayo score was 6.9; the average Mayo endoscopic subscore of 3 indicated severe illness; the average fecal calprotectin level was 1641 mg/kg; the average C-reactive protein level was 4.2 mg/L; and the average baseline oral corticosteroid use rate was 43.1 percent. Both therapy groups had similar baseline demographic and illness characteristics. Nearly half (47.4%) of the patients who were receiving a biologic for the first time had previously failed two or more advanced therapy classes for UC, showing extremely refractory disease. Approximately 50% of the patients were receiving a biologic for the first time.
F.Adjusted treatment difference using the Cochran-Mantel-Haenszel weight and the Wald statistic in 1f.
g. Clinical remission: A Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy, a Mayo stool frequency subscore of 0 or 1 and not increased from baseline.
h. Rectal bleeding subscore of 01 and a stool frequency subscore of 0 or 1 and not increased from baseline indicate symptomatic remission.
i. Clinical response: A modified Mayo score reduction of 30 percent and 2 points from baseline, with either a rectal bleeding subscore reduction of 1 point from baseline or a rectal bleeding subscore of 0 or 11.
j. Endoscopic improvement: A subscore of 0 or 1 for the endoscopy with no friability evident.
K. Histo-endoscopic mucosal improvement: Achieving both histologic (neutrophil infiltration in 5% of crypts, no crypt destruction, and absence of erosions, ulcerations, or granulation tissue, as measured by the Geboes grading system, i.e., Geboes score 3.1) and endoscopic (endoscopy subscore of 0 or 1, with no friability present on the endoscopy) improvement.
l. Endoscopic normalization: A subscore of 01 for endoscopy
About Digestive Disease Week® (DDW)
The largest international conference for specialists in gastroenterology, hepatology, endoscopy, and gastrointestinal surgery is known as Digestive Disease Week® (DDW). DDW is an in-person and online meeting from May 6–9, 2023, that is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT). More than 3,100 abstracts and hundreds of seminars on the most recent developments in GI research, medicine, and technology are presented during the meeting. Visit www.ddw.org for further details.
The QUASAR Study (NCT04033445) is discussed
The goal of the QUASAR study is to provide evidence for the safety and efficacy of guselkumab in the treatment of moderately to highly active UC. The study assesses the long-term TREMFYA therapy overall. At particular time points, the efficacy, safety, pharmacokinetics, immunogenicity, and biomarkers are evaluated.3 An evaluation of the effectiveness and safety of TREMFYA, an interleukin-23 p19 subunit antagonist, as induction therapy in patients with moderately to severely active UC who had an inadequate response or intolerance to conventional (e.g., thiopurines or corticosteroids) and/or advanced therapies (e.g., tumor necrosis factor-alpha antagonists, vedolizumab, or tofa), is being conducted as part of the 1
With regards to Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a catch-all name encompassing Crohn’s disease (CD) and ulcerative colitis (UC), two disorders that result in persistent GI tract inflammation.6 Long-lasting inflammation causes GI tract damage.6 Although the precise etiology of IBD is unknown, it could be due to a genetic predisposition or the immune system’s reaction to environmental factors.6 Constant diarrhea, abdominal pain, rectal bleeding, bloody stools, weight loss, and weariness are just a few of the symptoms that might occur.6
About Ulcerative Colitis
The large intestine, often known as the colon, is affected by the chronic disease ulcerative colitis (UC), in which the colon’s lining becomes inflamed and produces microscopic open sores or ulcers that secrete pus and mucus.7 It is the outcome of an overreactive immunological response.7 While there are many different symptoms, some include looser, more frequent bowel motions, chronic diarrhea, stomach pain, bloody stools, loss of appetite, weight loss, and exhaustion.8
About TREMFYA® (guselkumab)
The first fully human monoclonal antibody to be approved, TREMFYA was created by Janssen. It targets the p19 subunit of interleukin (IL)-23 and prevents it from interacting with the IL-23 receptor.9 Inflammatory illnesses like moderate to severe plaque psoriasis (PsO) and active psoriatic arthritis (PsA) are largely driven by IL-23.9 TREMFYA has received approval for the treatment of adult patients with active PsA as well as for the treatment of adults with moderate to severe plaque PsO who are candidates for systemic therapy (injections or pills) or phototherapy (treatment with ultraviolet light).
9 The treatment of moderate to severe plaque PsO in adults who are candidates for systemic therapy as well as the treatment of active PsA in adults who have had an insufficient response to or have been intolerable to a prior disease-modifying antirheumatic drug therapy are also approved uses for it in the EU.9
The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to TREMFYA®.
Important Safety Information
What is the most important information I should know about TREMFYA®?
TREMFYA® is a prescription medicine that may cause serious side effects, including:
Serious Reactions to Allergens. If you experience any of the signs of a severe allergic reaction listed below, stop using TREMFYA® and seek immediate emergency medical attention:
fainting, feeling lightheaded, and dizziness (low blood pressure)
Your face, eyelids, lips, tongue, or throat swelling, difficulty breathing, or tightness in your throat
chest constriction
itching, hives, and skin rash
Infections. TREMFYA® may reduce your immune system’s capacity to fight infections and raise your chance of contracting them. Before beginning TREMFYA® medication, your doctor should do an infection and tuberculosis (TB) check on you. If you have a history of TB or have active TB, your doctor may decide to treat you for TB first. During and after TREMFYA® therapy, your doctor should keep a close eye out for any TB signs and symptoms.
If you suspect you may have an infection or are exhibiting symptoms of an illness, such as:
muscular aches, chills, or a fever
weight loss cough warm, red, or painful skin or sores on your body other than psoriasis shortness of breath blood in your phlegm (mucus) burning in the urination or urinating more frequently than usual
If you have ever experienced a severe adverse response to guselkumab or any of the other ingredients in TREMFYA®, do not take it.
Inform your healthcare provider of all of your medical conditions prior to taking TREMFYA®, particularly if you:
experience any of the ailments or signs described in the section titled “What is the most important information I should know about TREMFYA®?”
possess an infection that won’t go away or keeps returning.
either they or a close friend or family member who has TB.
have recently had a vaccination or have one scheduled for them. Live vaccinations shouldn’t be given to you while you are getting TREMFYA® treatment.
are expecting or intend to get pregnant. The safety of TREMFYA® during pregnancy is unknown.
either currently breastfeed or want to do so. If TREMFYA® enters your breast milk is unknown.
All of the medications you use, including prescription and over-the-counter medications, vitamins, and herbal supplements, should be disclosed to your healthcare professional.
What potential negative effects could TREMFYA® have?
The negative effects of TREMFYA® could be really bad. What is the most crucial information regarding TREMFYA® that I need to be aware of?
Upper respiratory infections, headaches, injection site responses, joint discomfort (arthralgia), diarrhea, gastroenteritis, fungal skin infections, herpes simplex infections, and bronchitis are among the most frequent adverse effects of TREMFYA®.
These are not all of the potential TREMFYA® adverse effects. For medical advice about side effects, contact your doctor.
Follow your healthcare provider’s instructions for using TREMFYA® exactly.
Please read the entire prescribing information, including the TREMFYA® medication guide, and go through any concerns you have with your doctor.
You are urged to inform the FDA of any harmful side effects from prescription medications. Call 1-800-FDA-1088 or go to www.fda.gov/medwatch.
Regarding the Johnson & Johnson Janssen Pharmaceutical Companies
At Janssen, we’re working to eradicate disease in the future. We are the Pharmaceutical Companies of Johnson & Johnson, working assiduously to make that future a reality for patients all around the world by battling disease with science, enhancing access with inventiveness, and curing hopelessness with heart. Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension are the areas of medicine where we can have the most impact.
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