Phase 4 Data Offer New Insights into TNF Non-responders Actively Switched to REMICADE
ATLANTA, GA, USA | November 8, 2010 | Patients with active moderate to severe rheumatoid arthritis (RA) inadequately responding to either etanercept (Enbrel®) or adalimumab (Humira®) and who were actively switched to REMICADE® (infliximab) demonstrated significant improvement from baseline at week 10, and sustained response through week 26 in an open label study. These week 26 results from the RESTART study were presented for the first time at the largest rheumatology medical meeting in the United States.
"These findings offer new insights into actively switching patients not responding to one TNF blocker to another therapy in the class, and in this case REMICADE," said Roy Fleischmann, MD, University of Texas/Southwestern Medical Center and lead investigator. "The data from the RESTART study show that there are patients switched to REMICADE who demonstrate immediate benefits, including improvements in disease activity and physical function."
Patients who had an inadequate response (as measured by Disease Activity Score (DAS) 28 of at least 3.6 and at least 6 swollen and 6 tender joints) while receiving methotrexate and either etanercept or adalimumab were maintained on their stable dose of methotrexate and were actively switched to REMICADE 3 mg/kg. Patients who did not achieve or lost response had their dose titrated by 2 mg/kg. At week 10, nearly half of REMICADE-treated patients (49.7 percent) achieved clinical response as evaluated by the European League Against Rheumatism (EULAR) response criteria. The EULAR response criteria are based on the assessment of disease activity using the DAS28 score, a statistically-derived index consisting of number of tender joints, number of swollen joints, erythrocyte sedimentation rate and global assessments of disease activity.
At week 26, improvements were sustained (51.8 percent) with REMICADE maintenance dosing. Similarly, improvements in American College of Rheumatology (ACR) 20, ACR 50 and ACR 70 scores were reported at week 10 and were sustained through week 26. Additionally, by week 26 of the study, more than half of patients demonstrated a clinical improvement, as evaluated by the EULAR response criteria, with 48.3 percent of patients previously treated with etanercept and 57.1 percent of patients previously treated with adalimumab achieving a EULAR response.
Patients in the study also sustained improvements in physical function, as measured by the Health Assessment Questionnaire (HAQ), improving 0.223 from baseline levels (p<0.001). HAQ assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and other activities of daily living), scoring their responses from 0 to 3.
About the RESTART Study
The Phase 4 multicenter, open-label, assessor-blinded, active switch study evaluated 197 patients with moderate to severe rheumatoid arthritis who had an inadequate response, assessed as having a DAS28 score of at least 3.6 and at least 6 swollen and 6 tender joints, to treatment with etanercept (N=120) or adalimumab (N=77). Patients were assigned to receive REMICADE 3 mg/kg at weeks 0, 2 and 6, typically 1 and 2 weeks following their last dose of etanercept or adalimumab, respectively. Dosage was increased by 2 mg/kg at 14 and/or 22 weeks for those who did not achieve or lost response. Improvements from baseline were assessed at weeks 10 and 26 evaluating EULAR response (the primary endpoint at week 10) and improvement in arthritis symptoms (ACR response), disease activity (DAS28 scores) and physical function (HAQ scores).
Treatment with REMICADE was generally well-tolerated with no new safety signals reported. At least one adverse event (AE) was reported in 70.4 percent of patients, with at least one serious AE reported in 4.9 percent of patients; 6.9 percent of patients experienced at least one infusion reaction.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory condition that is often characterized by symptoms that include pain, stiffness and inflammation, and in some cases, joint destruction and disability. The Arthritis Foundation estimates that approximately 1.3 million people in the United States are living with RA, the majority of whom are women. For more information visit the Arthritis Foundation.
About REMICADE
REMICADE was the first anti-TNF-alpha treatment to be approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. REMICADE has demonstrated broad clinical utility with indications in Crohn’s disease (CD), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), ulcerative colitis (UC), pediatric Crohn’s disease (PCD) and psoriasis (PsO). The safety and efficacy of REMICADE have been well established in clinical trials over the past 17 years and through commercial experience with more than one million patients treated worldwide.
In the U.S., REMICADE is approved for the following indications:
* Reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA, when administered in combination with methotrexate.
* Reducing signs and symptoms in patients with active AS.
* Reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active CD who have had an inadequate response to conventional therapy.
* Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD.
* Reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy.
* Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with PsA.
* Treatment of adult patients with chronic severe plaque PsO who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.
REMICADE is unique among available anti-TNF biologic therapies. It is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. REMICADE is a two-hour infusion administered every 4 or 8 weeks (indication-dependent), following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients may require as few as six treatments each year as maintenance therapy.
IMPORTANT SAFETY INFORMATION FOR REMICADE
Only your doctor can recommend a course of treatment after checking your health condition. REMICADE (infliximab) can cause serious side effects such as lowering your ability to fight infections. There are reports of serious infections caused by viruses, fungi or bacteria that have spread throughout the body, including tuberculosis (TB) and histoplasmosis. Some of these infections have been fatal. Your doctor should monitor you closely for signs and symptoms of TB during treatment with REMICADE.
Unusual cancers have been reported in children and teenage patients taking TNF-blocker medicines. A rare form of fatal lymphoma has occurred mostly in teenage or young adult males with Crohn’s disease or ulcerative colitis who were taking REMICADE and azathioprine or 6-mercaptopurine. For children and adults taking TNF blockers, including REMICADE, the chances of getting lymphoma or other cancers may increase.
You should discuss any concerns about your health and medical care with your doctor.
What should I tell my doctor before I take REMICADE?
You should let your doctor know if you have or ever had any of the following:
* Tuberculosis (TB) or have been near someone who has TB. Your doctor will check you for TB with a skin test. If you have latent (inactive) TB, you will begin TB treatment before you start REMICADE.
* Lived in a region where certain fungal infections like histoplasmosis or coccidioidomycosis are common.
* Infections that keep coming back, have diabetes or an immune system problem.
* Any type of cancer or a risk factor for developing cancer, for example, chronic obstructive pulmonary disease (COPD) or had phototherapy for psoriasis.
* Heart failure or any heart condition. Many people with heart failure should not take REMICADE.
* Hepatitis B virus (HBV) infection or think you may be a carrier of HBV.
* Nervous system disorders (like multiple sclerosis or Guillain-Barre syndrome).
Also tell your doctor about any medications you are taking, including vaccines or Kineret (anakinra), and if you are pregnant, plan to become pregnant or are nursing. Adults and children should not receive a live vaccine while taking REMICADE.
What should I watch for and talk to my doctor about before or while taking REMICADE?
The following serious (sometimes fatal) side effects have been reported in people taking REMICADE.
You should tell your doctor right away if you have any of the signs listed below:
* Infections (like TB, blood infections, pneumonia)—fever, tiredness, cough, flu, or warm, red or painful skin or any open sores. REMICADE can make you more likely to get an infection or make any infection that you have worse.
* Lymphoma, or any other cancers in adults and children.
* Heart failure—new or worsening symptoms, such as shortness of breath, swelling of your ankles or feet, or sudden weight gain.
* Reactivation of HBV—feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.
* Liver injury—jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe tiredness.
* Blood disorders—fever that doesn’t go away, bruising, bleeding or severe paleness.
* Nervous system disorders—numbness, weakness, tingling, changes in your vision or seizures.
* Allergic reactions during or after the infusion—hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills.
* Lupus-like syndrome—chest discomfort or pain that does not go away, shortness of breath, joint pain, rash on the cheeks or arms that gets worse in the sun. The more common side effects with REMICADE are respiratory infections (that may include sinus infections and sore throat), headache, rash, coughing and stomach pain.
* Psoriasis—new or worsening psoriasis such as red scaly patches or raised bumps on the skin that are filled with pus.
Please read important information about REMICADE, including full U.S. prescribing information and Medication Guide, at www.remicade.com.
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 Centocor Ortho Biotech, Inc.
Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology, and oncology. Built upon a pioneering history, Centocor Ortho Biotech harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care. For more information about Centocor Ortho Biotech, visit www.CentocorOrthoBiotech.com.
SOURCE: Centocor Ortho Biotech Inc.
