The Janssen Pharmaceutical Companies of Johnson & Johnson today announced efficacy and safety data for STELARA® (ustekinumab) in Crohn's disease (CD) and ulcerative colitis (UC),1-4 including data from the SEAVUE study, the first head-to-head study of biologic therapies in patients with CD, presented in a Clinical Science Late-Breaking Abstract Plenary session.1 SEAVUE data showed treatment with STELARA demonstrated high rates of clinical remission, corticosteroid-free remission, clinical response, and endoscopic response through one year in biologic-naïve patients with moderately to severely active CD, although the primary endpoint of statistical superiority versus adalimumab was not demonstrated.1 These head-to-head data are one of 20 abstracts Janssen presented from the Company's gastroenterology pipeline and portfolio at DDW Virtual 2021, which took place May 21-23.1-4
"As the first head-to-head study of biologic therapies in Crohn's disease, SEAVUE is filling an important knowledge gap in the gastrointestinal community," said Bruce E. Sands, M.D., M.S., Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Hospital and the Dr. Burrill B. Crohn Professor of Medicine (Gastroenterology), at the Icahn Institute for Medicine at Mount Sinai, and SEAVUE study principal investigator. "SEAVUE has generated data that confirm STELARA as an important option for people living with moderately to severely active Crohn's disease who are new to biologic therapy."
STELARA vs. adalimumab efficacy and safety in biologic-naïve CD patients through one year (Presentation #775d): The SEAVUE study examined a total of 386 patients with moderately to severely active CD. Patients were randomized 1:1 to treatment with STELARA approximately 6 mg/kg intravenous (IV) at baseline, then 90 mg subcutaneous (SC) every eight weeks (q8w), or treatment with adalimumab 160/80 mg SC at baseline/week two, then 40 mg SC every two weeks per the U.S. Food and Drug Administration-approved regimens without dose modifications. Results did not show statistically significant differences:
"Until now, there have been no head-to-head trials comparing the safety and efficacy of prescription biologics to treat Crohn's disease, a chronic condition that can cause persistent and debilitating symptoms which can have a profound impact on a person's daily life," said Andrew Greenspan, M.D., Vice President, Immunology Medical Affairs, Janssen Scientific Affairs, LLC. "Armed with this new clinical trial data, doctors have a compelling option in STELARA for appropriate patients living with Crohn's disease."
Safety of STELARA in IBD: Pooled Safety Analysis Through Five Years in CD and Two Years in UC (Presentation #129): Safety data from six Phase 2/3 studies in CD patients (through five years) and UC patients (through two years) treated with STELARA (2,575 patients with 3,960 patient-years [PYs] of follow-up) and placebo (1,390 patients with 916 PYs of follow-up) were pooled.
Results showed the STELARA safety profile was favorable and consistent with the previously reported safety profile in inflammatory bowel disease patients through one year and the well-established safety profile across all approved indications for STELARA. Rates for the number of events per 100 PYs of follow-up for AEs (390.70 PYs for STELARA vs. 488.75 PYs for placebo), serious AEs (21.57 PYs for STELARA vs. 29.57 PYs for placebo), infections (98.62 PYs for STELARA vs. 109.56 PYs for placebo), serious infections (4.17 PYs for STELARA vs. 5.35 PYs for placebo), malignancy (0.45 PYs for STELARA vs. 0.33 for placebo), and major adverse cardiac events (MACE) (.30 PYs for STELARA vs. 0.33 PYs for placebo) were similar between placebo and STELARA.
Long-term (Five-Year) Maintenance of Clinically Meaningful Improvement in Health-Related Quality of Life (HRQoL) in Patients with Moderate to Severe CD Treated with STELARA in the IM-UNITI Long-term Extension Study (Presentation #Sa576): Results of the long-term extension of the IM-UNITI placebo-controlled maintenance study showed treatment with STELARA 90 mg every 12 weeks (q12w) or 90 mg q8w was effective at maintaining improvements in HRQoL through five years (252 weeks) that were first achieved during STELARA induction therapy in patients with moderately to severely active CD.
The percentage of patients who achieved clinically meaningful improvements in the Inflammatory Bowel Disease Questionnaire (IBDQ)d total score at week 252 was 40.8 percent for STELARA 90 mg q12w and 43.2 percent for STELARA 90 mg q8w. Clinically meaningful improvement was also observed for both STELARA regimens in Medical Outcomes Study 36-Item Short Form (SF-36)e Physical and Mental component summary [PCS and MCS] scores.f SF-36 PCS scores were: STELARA 90 mg q12w, 37.5 percent; 90 mg q8w, 37.7 percent. MCS scores were: STELARA 90 mg q12w, 33.9 percent; 90 mg q8w, 31 percent during the same period.
The Real-World Effectiveness of STELARA in the Treatment of CD (Presentation #611):
A real-world, retrospective, multicenter, consortium study evaluated cumulative rates of clinical and endoscopic remission of STELARA is a total of 1,113 patients with CD, the largest real-world cohort assessing STELARA effectiveness to date. 90 percent of patients had prior anti-tumor necrosis factor (TNF) exposure and 64.5 percent had prior exposure to treatment with at least two prior biologics and a median follow-up of 386 days.
Results showed 40 percent of patients achieved clinical remission through 12 months. Cumulative rates of steroid-free, endoscopic, and radiographic remission at 12 months were 32 percent, 39 percent, and 30 percent, respectively. Rates of clinical and endoscopic remission were lower with an increasing number of prior biologic exposures. Notably, the greatest treatment effect of STELARA was seen in biologic-naïve patients with 63 percent and 55 percent of patients achieving clinical and endoscopic remission, respectively, by 12 months.
"We are pleased to continue to build upon and reinforce the strength of Janssen's gastroenterology portfolio with our promise to advance treatment options for patients living with inflammatory bowel disease," said Jan Wehkamp, M.D., Vice President, Gastroenterology Disease Area Leader, Janssen Research & Development, LLC. "The strong body of scientific evidence for STELARA is the result of our long-term commitment to studying STELARA comparatively and in a variety of clinical settings to provide doctors and their patients with data that can help inform treatment decisions."
a. Dr. Bruce Sands is a paid consultant for Janssen. He has not been compensated for any media work.
b. SES-CD evaluates the presence or absence of endoscopic healing of the intestinal mucosa. The SES-CD is scored based on four endoscopic variables (area of affected surface, presence and size of ulcers, extent of ulcerated surface, and presence of stenoses) in the five intestinal segments. The total SES-CD score range is 0–60, with each section ranging from 0 to 12 points.5
c. Clinically meaningful improvement is defined as an IBDQ change ≥16 points or change in SF-36 MCS or PCS score ≥5 points.3
d. IBDQ is a 32-item questionnaire with four dimensions (bowel symptoms, systemic symptoms, emotional function, and social function [total score 32 to 224]).3
e. SF-36 is a set of generic, coherent, and easily administered quality-of-life measures reliant upon patient self-reporting.6
f. PCS and MCS are each scored 0 to 100; higher scores indicate better quality of life.3
Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers, and academics in the fields of gastroenterology, hepatology, endoscopy, and gastrointestinal surgery. 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), DDW is a fully virtual meeting from May 21-23, 2021. The meeting showcases more than 2,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine, and technology. More information can be found at www.ddw.org.
SEAVUE is a Phase 3b, multicenter, randomized, blinded, active-controlled study to compare the efficacy and safety of STELARA to adalimumab in the treatment of biologic-naïve patients with moderately to severely active Crohn's disease. The study consists of screening (within 1 to 5 weeks prior to week 0), treatment phase (weeks 0 to 52), and follow-up phase (up to week 76). Study assessments include Crohn's Disease Activity Index (CDAI), video ileocolonoscopy; CD-related healthcare utilization; patient-reported outcomes (PROs); laboratory evaluations; biomarkers; review of concomitant medications and adverse events (AEs); and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants were randomly assigned to receive either ustekinumab or adalimumab. No participants were treated with placebo only.
IM-UNITI, a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study, evaluated the efficacy and safety of STELARA maintenance therapy in adult patients with moderate to severe Crohn's disease. Patients who had responded to a single IV dose of STELARA in the UNITI-1 or UNITI-2 induction studies were randomized equally to receive maintenance SC STELARA 90 mg q8w or q12w, or placebo. There were 1,281 patients enrolled in the maintenance study. In randomized patients who met loss of response criteria between weeks 8–32, a one-time dose adjustment to 90 mg q8w occurred. All patients completing week 44 were eligible to enter the long-term extension program, continuing their current regimen up to week 252.
About Crohn's disease
CD is one of the two main forms of inflammatory bowel disease, which affects an estimated three million Americans. CD is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet, or other environmental factors. Symptoms of CD can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss, and fever. There is currently no cure for CD.
About Ulcerative Colitis
More than five million people worldwide are living with CD and UC—commonly known as inflammatory bowel disease. UC affects nearly 907,000 people in the U.S., with approximately 38,000 new cases diagnosed each year. UC is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. It is the result of an abnormal response by the body's immune system. Symptoms vary but may include loose and more urgent bowel movements, persistent diarrhea, abdominal pain, bloody stool, loss of appetite, weight loss, and fatigue.
About STELARA® (ustekinumab)16
STELARA® (ustekinumab) is a fully human monoclonal antibody and is the first biologic treatment to selectively inhibit the interleukin (IL)-12 and IL-23 pathways. STELARA is approved in the United States for the treatment of 1) adults and children six years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy; 2) adult patients (18 years or older) with active psoriatic arthritis, used alone or in combination with methotrexate (MTX); 3) adult patients (18 years and older) with moderately to severely active Crohn's disease; 4) adult patients (18 years and older) with moderately to severely active ulcerative colitis.
The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA®.
IMPORTANT SAFETY INFORMATION
STELARA® is a prescription medicine that affects your immune system. STELARA® can increase your chance of having serious side effects including:
STELARA® may lower your ability to fight infections and may increase your risk of infections. While taking STELARA®, some people have serious infections, which may require hospitalization, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses.
You should not start taking STELARA® if you have any kind of infection unless your doctor says it is okay.
Before starting STELARA®, tell your doctor if you:
After starting STELARA®, call your doctor right away if you have any symptoms of an infection (see above). STELARA® can make you more likely to get infections or make an infection that you have worse. People who have a genetic problem where the body does not make any of the proteins interleukin 12 (IL–12) and interleukin 23 (IL–23) are at a higher risk for certain serious infections that can spread throughout the body and cause death. People who take STELARA® may also be more likely to get these infections.
STELARA® may decrease the activity of your immune system and increase your risk for certain types of cancer. Tell your doctor if you have ever had any type of cancer. Some people who had risk factors for skin cancer developed certain types of skin cancers while receiving STELARA®. Tell your doctor if you have any new skin growths.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
RPLS is a rare condition that affects the brain and can cause death. The cause of RPLS is not known. If RPLS is found early and treated, most people recover. Tell your doctor right away if you have any new or worsening medical problems including headaches, seizures, confusion, and vision problems.
Serious Allergic Reactions
Serious allergic reactions can occur. Stop using STELARA® and get medical help right away if you have any symptoms of a serious allergic reaction such as: feeling faint, swelling of your face, eyelids, tongue, or throat, chest tightness, or skin rash.
Cases of lung inflammation have happened in some people who receive STELARA® and may be serious. These lung problems may need to be treated in a hospital. Tell your doctor right away if you develop shortness of breath or a cough that doesn't go away during treatment with STELARA®.
Before receiving STELARA®, tell your doctor about all of your medical conditions, including if you:
Tell your doctor about all the medicines you take, including prescription and over–the–counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
When prescribed STELARA®:
Common side effects of STELARA® include nasal congestion, sore throat, and runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, stomach pain, diarrhea, and joint pain. These are not all of the possible side effects with STELARA®. Tell your doctor about any side effects that you experience. Ask your doctor or pharmacist for more information.
Please read the full Prescribing Information and Medication Guide for STELARA® and discuss any questions you have with your doctor.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1–800–FDA–1088.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where the disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
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Janssen Research & Development, LLC is a part of the Janssen Pharmaceutical Companies of Johnson & Johnson.