Please read these Terms of Service (the “Agreement”) carefully. By using the Services (as defined below), you agree to this Agreement. We recommend that you print a copy of this Agreement for future reference. We retain the right to make changes, as outlined below.
This Agreement is between you and Janssen Biotech, Inc. (“Company” or “we” or “us” or “our”) concerning your use of the website located at https://remicadehcp.com (the “Site”) or the mobile software application in connection with which you are accessing this Agreement (the “App”) (collectively, the “Services”).
If you are not willing to accept the terms and conditions in the Agreement, we ask that you not access or use the Services or post or submit any materials on them or order any items from them. Please review our Privacy Policy located at https://remicadehcp.com/privacy-policy for details about what information we collect and how we use it.
This site is intended for and directed to residents of the United States and its territories. You affirm that you are of legal age to enter into this Agreement. This website (or app) is not intended for use by persons under the age of 18. If you are under 18 years old, you may not use this website (or app) or provide the Company with any personally identifiable information. If this site includes the ability to purchase products or services, in order to utilize the purchasing function, you must be the age of majority in your state.
If you are using the Services on behalf of, or for the benefit of, any organization with which you are associated, then you agree to the terms of this Agreement on behalf of yourself and such organization, and you confirm that you have the legal authority to bind such organization to this Agreement. References to “you” and “your” in this Agreement will refer to both you and any such organization.
1. Our Right to Make Changes. We may change this Agreement from time to time (for any reason, such as changes in the functions or services offered by this Site or to reflect a change in the law) by notifying you of such changes by any reasonable means and by making available a revised Agreement through the Services. Any such changes will not apply to any dispute between you and us arising prior to the date on which we posted the revised Agreement incorporating such changes or otherwise notified you of such changes. Your clicking or tapping “OK” or “Agree” (or a similar term) in connection with this Agreement or your use of the Services following any changes will constitute your acceptance of such changes. The “Last Updated” legend above indicates when this Agreement was last changed.
To the extent permitted by applicable law, we may, at any time and without liability, modify or discontinue all or part of the Services (e.g., to reflect changes in the relevant laws, to protect the security of the Services or to implement reasonable technical adjustments and improvements, to modify the services and functions provided by the Site); charge, modify or waive any fees required to use the Services where reasonably necessary; or offer opportunities to some or all users, at our sole discretion. We will seek to notify you by reasonable means of (i) any modifications that will have a material adverse effect on your use of the Services, taken as a whole; and (ii) any material increase in the fees charged by us to use the Services.
2. Information Disclaimer
The information, including any advice and recommendations provided as part of the Services is intended solely for educational and informational purposes. It is not intended as medical or healthcare advice, or to be used for medical diagnosis or treatment for any individual problem. It is also not intended as a substitute for professional advice and services from a qualified healthcare provider familiar with your unique facts. Always seek the advice of your doctor or other qualified healthcare provider regarding any medical condition and before starting any new treatment. Your use of the Services is subject to the additional disclaimers and caveats that may appear throughout the Services.
We assume no responsibility for any consequence relating directly or indirectly to any action or inaction you take based on the information, or other material provided as part of the Services. While we strive to keep the information provided by the Services to be accurate, complete, and up-to-date, we do not give any assurances, and will not be responsible for, any damage or loss related to the accuracy, completeness, or timeliness of the information provided as part of the Services.
3. Information Submitted Through the Services. Your submission of information through the Services is governed by our Privacy Policy, located at https://remicadehcp.com/privacy-policy.
4. Jurisdictional Issues. The Services may not be appropriate or available for use in some jurisdictions. Any use of the Services is at your own risk, and you must comply with all applicable laws, rules and regulations in doing so. We may limit the availability of the Services at any time, in whole or in part, to any person or geographic area that we choose, in our sole discretion, for valid reasons (e.g., to comply with relevant laws and regulatory requirements, to protect the security of the Services or to implement reasonable technical adjustments).
5. Acceptable Use and Rules of Conduct. You must not:
You are responsible for obtaining, maintaining and paying for all hardware, telecommunications and other services needed for you to use the Services.
6. Electronic Communications. The information communicated as part of the Services may constitute an electronic communication. When you communicate with us through the Services or via other forms of electronic media, such as e-mail, you are communicating with us electronically. You agree that we may communicate electronically, subject to local privacy and Anti-Spam laws, and that such communications, as well as notices, disclosures, agreements and other communications that we provide to you electronically, are equivalent to communications in writing and shall have the same force and effect as if they were in writing and signed by the party sending the communication.
7. Registration. You may need to register to use the Services. We may reject, or require that you change, any user name, password or other information that you provide. Your user name and password are for your personal use only. You are solely responsible for maintaining the confidentiality of your credentials and for restricting access to your mobile device, computer and/or other means of accessing the Services. We are not responsible for any use of your credentials caused by your failure to keep them confidential. You are solely responsible for all activities that occur under your account, either with or without your knowledge. You must promptly notify us of any unauthorized use of your credentials or account of which you become aware. We recommend that, to the extent you access the Services via a mobile device, you password protect said device.
You agree that any information you provide to us will be current, accurate and complete and that you will keep such information up to date by notifying us of any changes.
We reserve the right to terminate any account at any time in our sole discretion, including without limitation for any failure to comply with these Terms of Use, any fraud or abuse, or any misrepresentation that you or anyone using your account may make to us.
8. Profiles and Forums. You may be permitted to make available certain information or materials (each, a “Submission”) in connection with the Services, including on profile pages or interactive features. We have no control over and are not responsible for any Submissions, any use or misuse by any third party of Submissions or for your interactions with other users. Users are ultimately responsible for their own actions. If you choose to make your personal or other information publicly available through the Services, you do so at your own risk.
You acknowledge that any forums contain the opinions and views of other users. You acknowledge further that we are not responsible for the accuracy of any Submissions on the Site. You understand and agree that all Submissions are the sole responsibility of the person who posted the Submission. You understand and agree that you will evaluate, and bear all risks associated with, the use of any Submission, including any reliance on the accuracy, completeness or usefulness of such Submission.
9. Our Right to Use Submissions. Nothing in this Agreement transfers any ownership rights in your Submissions. For each Submission, you grant to us a worldwide, royalty-free, fully paid-up, non-exclusive, perpetual, irrevocable, transferable and fully sublicensable (through multiple tiers) license, without additional consideration to you or any third party, to reproduce, distribute, perform and display (publicly or otherwise), create derivative works of, adapt, modify, store and otherwise use, analyze and exploit such Submission, and to contact you about your Submission, in any format or media now known or hereafter developed, and for any purpose (including promotional purposes, such as testimonials and advertising).
We are free to use any ideas, concepts, know-how or techniques contained in or derived from any Submission for any purpose whatsoever, including developing, manufacturing and marketing products. Therefore, please do not submit or send to us any ideas, suggestion or materials that you wish to keep confidential or for which you expect to receive compensation. You will not have any claim against us with respect to any use or non-use of Submissions. When you submit Submissions, you understand that we will have the right, but not the obligation, to use, display and publish your name, photograph, likeness, voice, performance, biographical information and/or statements, throughout the world in perpetuity on the Services and on any affiliate or successor site or social media channels owned or operated by us or our affiliates. If we make use of any of these rights, you understand and agree that you shall not receive any other consideration, payment, notification or credit, nor will you have any approval over how we use them.
In addition, if you provide to us any ideas, proposals or suggestions (“Feedback”), we will deem such Feedback a Submission. You agree that Feedback is not confidential and that your provision of it is gratuitous, unsolicited and without restriction and does not place us under any obligation in respect of such Feedback.
You confirm that (a) you have all rights necessary to grant the licenses granted in this section, (b) your Submissions are complete and accurate, and (c) your Submissions and your provision of them to us are not fraudulent or otherwise in breach of any applicable law or any right of any third party. You further irrevocably waive (and consent to us performing any acts or omissions in relation to your Submissions and associated materials that may be inconsistent with) any “moral rights” or other rights with respect to attribution of authorship or integrity of materials regarding your Submission that you may have under any applicable law.
We may impose a maximum amount of storage for Submissions on the Services. We are not responsible for any loss or harm you may suffer as a result of any deletion or failure to store any messages, communications or other Submission associated with maintaining the maximum amount of storage.
10. Monitoring Use of the Service. We may (but have no obligation to) monitor, evaluate, alter or remove Submissions before or after they appear on the Services or analyze your access to or use of the Services. We may disclose information regarding your access to and use of the Services, the circumstances surrounding the transmission of Submissions, and personal information regarding users who make Submissions available, in each case in accordance with applicable law or a request by a court or law enforcement or other governmental authority, or otherwise in accordance with our Privacy Policy.
11. Your Right to Use the Services. You acknowledge that all intellectual property rights in the Services, including the Site and the App, belong to us or our licensors. You have no right in or to the Services other than the right to access them in accordance with this Agreement. Subject to your compliance with, and solely for the duration of, this Agreement: (a) you may view one copy of the Site on any single device, solely for your personal, non-commercial use; (b) we permit you, on a limited, non-exclusive, revocable, non-transferable, non-sublicensable basis, to install and use the App on a device that you own or control, solely for your personal, non-commercial use. The App is licensed (not sold) to you. If you fail to comply with this Agreement, you must immediately cease using the Services, and delete the App from your device. You are responsible for keeping your device secure and protecting it appropriately.
12. Company’s Proprietary Rights. We and our suppliers own the Services, which are protected by proprietary rights and laws, including all of our brand names, trademarks and service marks and any associated logos. All trade names, trademarks, service marks and logos (collectively, “Marks”) on the Services not owned by us are the property of their respective owners. You may not use our Marks in connection with any product or service that is not ours or in any manner that is likely to cause confusion. Nothing contained on the Services should be construed as granting any right to use any Marks without the express prior written consent of the owner.
13. Third Party Materials; Links. The Services may allow access to third-party information, products, services and other materials, including Submissions (collectively, “Third Party Materials”), and including any access via links. We do not control or endorse, and are not responsible for, any Third Party Materials. We have no obligation to monitor Third Party Materials, and we may block or disable access to any Third Party Materials at any time. Your access or use of Third Party Materials is at your own risk and is subject to any additional terms, conditions and policies applicable to such materials.
14. Additional Terms. Additional terms may govern certain features or content of the Services, such as offers, prize draws, competitions, contests and sweepstakes. By participating in any activity as part of the Services governed by additional terms, such as a prize draw, competition, contest or sweepstakes with Official Rules, you agree that you will be subject to those additional terms in addition to these Terms of Use.
15. Disclaimer of Warranties. To the fullest extent permitted under applicable law, the Services are made available to you on an “as is,” “where is” and “where available” basis, without any warranties or conditions of any kind, whether express, implied or statutory.
We disclaim all warranties with respect to the Services to the fullest extent permissible under applicable law, including the warranties of merchantability, fitness for a particular purpose, non-infringement and title.
To the fullest extent permissible under applicable law, and subject to any applicable terms and conditions or policies applicable to the use of Third Party Materials as set out in Section 13, Third Party Materials are made available to you on an “as is,” “where is” and “where available basis, without any warranties of any kind, whether express or implied. We disclaim all warranties with respect to Third Party Materials.
Without limiting the generality of the foregoing, to the fullest extent permissible under applicable law, we make no representation or warranty that the Services will be secure, that any user name, password or other security measure that you may use or allow others to use in connection with the Services will prevent unauthorized access to your Services account or related information, or that your Services account or related information will not be accessed or misused by any third party.
All disclaimers of any kind in this Agreement (including in this section and elsewhere in this Agreement) are made for the benefit of both Company and its affiliates and their respective shareholders, stockholders, directors, officers, employees, affiliates, agents, representatives, licensors, suppliers and service providers, and their respective successors and assigns collectively, the “Company Parties”.
While we take reasonable steps to try to maintain the timeliness, integrity and security of the Services, we cannot guarantee that they are or will remain updated, complete, correct or secure, or that access to them will be uninterrupted. The Services may include inaccuracies, errors and materials that conflict with this Agreement. Additionally, third parties may make unauthorized alterations to the Services. If you become aware of any such alteration, please use the link at Contact Us and provide a description of such alteration and its location on the Services.
16. LIMITATION OF LIABILITY.
Nothing in this agreement restricts, excludes or modifies or purports to restrict, exclude or modify any mandatory statutory consumer rights under applicable law.
With respect to any conditions, warranties or guarantees that cannot be excluded under applicable statutes, to the extent permitted by applicable law, our liability is limited (at our option) to the resupply or refund of the cost of the relevant portion of the Services.
To the fullest extent permitted under applicable law: (a) we will not be liable for any indirect, incidental, consequential, special, exemplary or punitive damages of any kind, or losses that were not reasonably foreseeable to you or us at the time you agreed to this Agreement, in each case arising out of or in connection with the Services or this Agreement, and under any contract, tort (including negligence), strict liability or other theory (collectively, “Indirect Losses”). Loss or damage is foreseeable if either it is obvious that it will happen or if, at the time the contract was made, both you and we knew it might happen.
Without limiting the foregoing, we will not be liable for indirect losses of any kind resulting from your use of or inability to use the Services or from any products or Third Party Materials, including from any Virus that may be transmitted in connection therewith.
The Company Parties do not exclude or limit in any way our liability to you where it would be unlawful to do so. This includes liability for death or personal injury caused by our negligence or the negligence of our employees, agents or subcontractors, for gross negligence or willful behavior, or for fraud or fraudulent misrepresentation.
Our maximum aggregate liability for all damages, losses and causes of action arising out of or in connection with the Services or this Agreement, whether in contract, tort (including negligence) or otherwise, will not exceed the greater of (a) the total amount, if any, paid by you to us to use the Services; and (b) ten United States dollars ($10).
All limitations of liability of any kind in this Agreement (including in this section and elsewhere in this Agreement) are made for the benefit of both Company and the Company Parties.
With respect to any conditions, warranties or guarantees that cannot be excluded under statute, to the extent permitted under applicable law, our liability is limited (at our option) to the resupply or refund of the cost of relevant services.
17. Third Party Claims. If we are sued by a third party as a result of your breach of this Agreement or your infringement of any Third Party Right, then, to the fullest extent permitted by applicable law, you will be responsible for all liabilities, damages, judgments, awards, losses, costs, expenses and fees (including attorneys’ fees) incurred by the Company Parties.
18. Termination. You may stop using the Services, and thereby terminate this Agreement, at any time. We may terminate or suspend your use of the Services if you do not comply with this Agreement, engage in any fraud or abuse, or if you or anyone using your account makes any misrepresentation to us. Where reasonable under the circumstances, we will provide you with at least twenty-four (24) hours’ prior notice of termination or suspension, provided that if we reasonably believe that you have materially breached this Agreement, we may immediately terminate or suspend you. Upon any termination or suspension, your right to use the Services will immediately cease, and we may, without liability to you or any third party, immediately deactivate or delete your user name, password and account, and all associated materials, without obligation to provide further access to such materials. Your obligations under this Agreement shall survive any expiration or termination of this Agreement.
19. Governing Law; Jurisdiction. Unless otherwise prescribed by applicable law, this Agreement is governed by and shall be construed in accordance with the laws of the State of New York, without regard to its principles of conflicts of law, and regardless of your location. All disputes between you and us arising out of or related to the Services or this Agreement, whether based in contract, tort, statute, fraud, misrepresentation or any other legal theory and including non-contractual disputes or claims, will be subject to the exclusive jurisdiction of the federal and state courts located in the State of New York, U.S.A., and you waive any jurisdictional, venue or inconvenient forum objections to such courts.
20. Filtering. Parental control protections (such as computer hardware, software or filtering services) are commercially available that may assist you in limiting access to material that may be harmful to or inappropriate for minors. Information identifying current providers of such protections (which we do not endorse) is available from https://en.wikipedia.org/wiki/Comparison_of_content-control_software_and_providers.
21. Information or Complaints. If you have a question or complaint regarding the Services, please use the link at Contact Us. California residents may reach the Complaint Assistance Unit of the Division of Consumer Services of the California Department of Consumer Affairs by mail at 1625 North Market Blvd., Sacramento, CA 95834, or by telephone at (916) 445-1254 or (800) 952-5210.
22. Copyright Infringement Claims. If you believe in good faith that materials available on the Services infringe your copyright, you may write to us by mail and request that we remove such material or block access to it. Please be precise about the identity and location of the allegedly infringing materials. If you believe in good faith that someone has wrongly filed a notice of copyright infringement against you, you may send us a written counter-notice. Notices and counter-notices must be sent through the link at Contact Us. In the United States, in addition to contacting us by clicking Contact Us, the Company’s Agent for complaints related to the Digital Millennium Copyright Act (DMCA) can be reached in writing at the following address:
Trademark Law Department
Johnson & Johnson
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
This address may also be used to contact us about copyright infringement claims in jurisdictions outside of the United States.
23. Export Controls. The Services are subject to U.S. export controls restrictions. We will not knowingly make the Services available to you if you are, and you confirm that you are, (a) located in, or a resident or a national of, any country subject to a U.S. government embargo or trade sanction (currently Cuba, Iran, Sudan, Syria, and the Crimea region of Ukraine) (see http://www.treasury.gov/resource-center/sanctions/Programs/Pages/Programs.aspx for more information on U.S. sanctions); or (b) on any of the U.S. government lists of restricted end users (for example, including the “Specially Designated Nationals” list available at http://www.treasury.gov/resource-center/sanctions/SDN-List/Pages/default.aspx).
24. Forward-Looking Statements. Statements appearing on the Services that concern us, our affiliates or our and their management and that are not historical facts are “Forward-Looking Statements.” Forward-Looking Statements are only predictions, and actual future events may differ materially from those discussed in any Forward-Looking Statement. Various external factors and risks affect our operations, markets, products, services and prices. These factors and risks are described in our current annual report filed with the SEC and in other filings we make with the SEC. You can access our most recent SEC filings via the SEC EDGAR system located at www.sec.gov, or you may obtain these filings directly from us at no charge. We disclaim any obligation or responsibility to update, revise or supplement any Forward-Looking Statement or any other statements appearing on the Services.
25. Other Important Terms. This Agreement does not, and shall not be construed to, create any partnership, joint venture, employer-employee, agency or franchisor-franchisee relationship between you and us. This Agreement is between you and us. Except as set forth in Sections 17, 18 and 27, no other person shall have any rights to enforce any of the terms of this Agreement. If any provision of this Agreement is found to be unlawful, void or for any reason unenforceable, that provision will be deemed severable from this Agreement and will not affect the validity and enforceability of any remaining provision. You may not assign, transfer or sublicense any or all of your rights or obligations under this Agreement without our prior written consent. We may assign, transfer or sublicense any or all of our rights or obligations under this Agreement without restriction. No waiver by either party of any breach or default under this Agreement will be deemed to be a waiver of any preceding or subsequent breach or default. Any heading, caption or section title contained herein is for convenience only, and in no way defines or explains any section or provision. All terms defined in the singular shall have the same meanings when used in the plural, where appropriate and unless otherwise specified. Any use of the term “including” or variations thereof in this Agreement shall be construed as if followed by the phrase “without limitation.” This Agreement, including any terms and conditions incorporated herein, is the entire agreement between you and us relating to the subject matter of this Agreement, and, in the absence of fraud, supersedes any and all prior or contemporaneous written or oral agreements or understandings between you and us relating to such subject matter. Notices to you (including notices of changes to this Agreement) may be made via posting to the Services or by e-mail (including in each case via links), or by regular mail. Without limitation, a printed version of this Agreement and of any notice given in electronic form shall be admissible in judicial or administrative proceedings based upon or relating to this Agreement to the same extent and subject to the same conditions as other business documents and records originally generated and maintained in printed form. Neither party will be responsible for any failure to fulfill any obligation due to any cause beyond its control.
26. Terms Required by Apple. In addition to your agreement with the foregoing terms and conditions, and notwithstanding anything to the contrary herein, the following provisions apply with respect to your use of any version of the App compatible with the iOS operating system of Apple Inc. (“Apple”). Apple is not a party to this Agreement and does not own and is not responsible for the App. Apple is not providing any warranty for the App except, if applicable, to refund the purchase price for it. Apple is not responsible for maintenance or other support services for the App and shall not be responsible for any other claims, losses, liabilities, damages, costs or expenses with respect to the App, including any third-party product liability claims, claims that the App fails to conform to any applicable legal or regulatory requirement, claims arising under consumer protection, privacy or similar legislation (including in connection with any use by the App of Apple’s HealthKit or HomeKit frameworks), and claims with respect to intellectual property infringement. Any inquiries or complaints relating to the use of the App, including those pertaining to intellectual property rights, must be directed to Company in accordance with the “Information or Complaints” section above. The license you have been granted herein is limited to a non-transferable license to use the App on an Apple-branded product that runs Apple’s iOS operating system and is owned or controlled by you, or as otherwise permitted by the Usage Rules set forth in Apple’s App Store Terms of Service, except that the App may be accessed and used by other accounts associated with the purchaser via Family Sharing or volume purchasing. In addition, you must comply with the terms of any third-party agreement applicable to you when using the App, such as your wireless data service agreement. Apple and Apple’s subsidiaries are third-party beneficiaries of this Agreement and, upon your acceptance of the terms and conditions of this Agreement, will have the right (and will be deemed to have accepted the right) to enforce this Agreement against you as a third-party beneficiary thereof; notwithstanding the foregoing, Company’s right to enter into, rescind or terminate any variation, waiver or settlement under this Agreement is not subject to the consent of any third party.
© Janssen Biotech, Inc. 2020 unless otherwise noted. All rights reserved.
Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.
Reported infections include:
The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.
Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including REMICADE®. These cases have had a very aggressive disease course and have been fatal. The majority of reported REMICADE® cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.
In clinical trials of all TNF blockers, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF blockers, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF blockers in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including REMICADE®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with REMICADE® compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between REMICADE® and cervical cancer cannot be excluded. Periodic screening should continue in women treated with REMICADE®.
The use of REMICADE® at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. REMICADE® is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of REMICADE® or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).
TNF blockers, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating REMICADE®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
In a randomized, placebo-controlled study in patients with moderate or severe heart failure (NYHA Functional Class III/IV), higher mortality rates and a higher risk of hospitalization were observed at Week 28 at a dose of 10 mg/kg and higher rates of cardiovascular events were observed at both 5 mg/kg and 10 mg/kg. There have been postmarketing reports of new onset and worsening heart failure, with and without identifiable precipitating factors. Patients with moderate or severe heart failure taking REMICADE® (≤5 mg/kg) or patients with mild heart failure should be closely monitored and treatment should be discontinued if new or worsening symptoms appear.
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.
REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Anaphylaxis, acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Medications for the treatment of hypersensitivity reactions should be available.
Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of REMICADE® infusion. Cases of transient visual loss have been reported during or within 2 hours of REMICADE® infusion. Monitor patients during infusion and if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.
TNF blockers, including REMICADE®, have been associated with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering REMICADE® in patients with these disorders and consider discontinuation if these disorders develop.
Concurrent use of REMICADE® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as REMICADE® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
Treatment with REMICADE® may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
Prior to initiating REMICADE®, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with REMICADE® due to the possibility of clinical infections, including disseminated infections.
At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to REMICADE®.
In clinical trials, the most common adverse reactions occurring in >10% of REMICADE®-treated patients included infections (eg, upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.
For more information, please see the full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion.
References: 1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247. 2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.
cp-62063v2
REMICADE® is indicated for:
Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.
Reported infections include:
The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.
Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including REMICADE®. These cases have had a very aggressive disease course and have been fatal. The majority of reported REMICADE® cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.
In clinical trials of all TNF blockers, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF blockers, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF blockers in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including REMICADE®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with REMICADE® compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between REMICADE® and cervical cancer cannot be excluded. Periodic screening should continue in women treated with REMICADE®.
The use of REMICADE® at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. REMICADE® is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of REMICADE® or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).
TNF blockers, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating REMICADE®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
In a randomized, placebo-controlled study in patients with moderate or severe heart failure (NYHA Functional Class III/IV), higher mortality rates and a higher risk of hospitalization were observed at Week 28 at a dose of 10 mg/kg and higher rates of cardiovascular events were observed at both 5 mg/kg and 10 mg/kg. There have been postmarketing reports of new onset and worsening heart failure, with and without identifiable precipitating factors. Patients with moderate or severe heart failure taking REMICADE® (≤5 mg/kg) or patients with mild heart failure should be closely monitored and treatment should be discontinued if new or worsening symptoms appear.
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.
REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Anaphylaxis, acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Medications for the treatment of hypersensitivity reactions should be available.
Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of REMICADE® infusion. Cases of transient visual loss have been reported during or within 2 hours of REMICADE® infusion. Monitor patients during infusion and if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.
TNF blockers, including REMICADE®, have been associated with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering REMICADE® in patients with these disorders and consider discontinuation if these disorders develop.
Concurrent use of REMICADE® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as REMICADE® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
Treatment with REMICADE® may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
Prior to initiating REMICADE®, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with REMICADE® due to the possibility of clinical infections, including disseminated infections.
At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to REMICADE®.
In clinical trials, the most common adverse reactions occurring in >10% of REMICADE®-treated patients included infections (eg, upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.
For more information, please see the full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion.
References: 1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247. 2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.
cp-62063v2
REMICADE® is indicated for:
Targan et al conducted a multicenter, randomized, double-blind trial in 108 patients with moderately to severely active CD (baseline CDAI ≥220 and ≤400) unresponsive to conventional therapy. Patients were randomized to receive a single infusion of placebo (n=25) or REMICADE® 5 mg/kg IV (n=27), 10 mg/kg IV (n=28), or 20 mg/kg IV (n=28). The primary endpoint was clinical response at Week 4.5
Note: The recommended dose of REMICADE® is 5 mg/kg given as an IV induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg IV every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn’s disease.1
ACCENT I is a 1-year, multicenter, randomized, double-blind trial of REMICADE® in 545 patients with moderately to severely active CD (CDAI ≥220 and ≤400). All patients received an initial dose of REMICADE® 5 mg/kg IV. Patients were then randomized based on clinical response at Week 2 to 1 of 3 treatment groups through Week 541,6:
The coprimary endpoints of the trial were the proportion of patients responding at Week 2 who were in remission at Week 30 and time to loss of response through Week 54.1,6
Note: The recommended dose of REMICADE® is 5 mg/kg given as an IV induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg IV every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn’s disease.1
Results from SONIC, a multicenter, randomized, double-blind, controlled, phase IIIb trial of 508 patients with moderately to severely active CD (baseline CDAI ≥220 and ≤450). At baseline, mean CDAI score for all patients was 287; median duration of CD ranged from 2.2 to 2.4 years. Patients were randomly assigned to 1 of 3 treatment groups through Week 30. In the primary study phase, patients received REMICADE® 5 mg/kg or placebo infusions at Weeks 0, 2, 6, 14, and 22; patients also received AZA capsules at a dose of 2.5 mg/kg/day or placebo capsules daily through Week 30. Patients completing treatment through Week 30 (main study) were eligible to enter the study extension if, in the opinion of the investigator, the patient could benefit from continued treatment. Patients eligible for participation in the extension (N=280) continued to receive their initial treatment through Week 50. The Week-50 analysis included patients who did not enter the study extension. These patients were assumed nonresponders and not to be in steroid-free remission at Week 50. The primary endpoint of the study was the proportion of patients in corticosteroid-free remission at Week 26. Secondary endpoints included mucosal healing at Week 26 and corticosteroid-free remission at Week 50. Monitoring for adverse events was performed through Week 54.
REACH (A Randomized, multicenter, open-label study to Evaluate the safety and efficacy of Anti-TNF-α Chimeric monoclonal antibody in pediatric subjects with moderate to severe Crohn's disease) was a controlled trial that evaluated the safety and efficacy of REMICADE® in 112 pediatric patients aged 6 to 17 years with moderately to severely active CD. All patients received induction dosing of 5 mg/kg IV REMICADE® at Weeks 0, 2, and 6. At Week 10, 103 patients were randomized to a maintenance regimen of REMICADE® 5 mg/kg IV given either every 8 weeks or every 12 weeks. Induction of clinical response, the primary endpoint, was evaluated 10 weeks after the 3-dose induction regimen (Weeks 0, 2, and 6). At Week 54, clinical response, clinical remission, and change from baseline in average daily corticosteroid use were evaluated as secondary efficacy endpoints.5
Note: REMICADE® 5 mg/kg IV every 12 weeks is not an approved maintenance dose for REMICADE®.1
The safety and efficacy of REMICADE® were evaluated in the Active Ulcerative Colitis Trial (ACT 1) (N=364), a randomized, double-blind, placebo-controlled, multicenter trial conducted in patients with moderately to severely active ulcerative colitis who had an inadequate response or were intolerant to conventional therapy. Patients presented with a Mayo score between 6 and 12, and an endoscopy subscore of ≥2. Prior failed or intolerable therapies in ACT 1 included oral corticosteroids, 6-mercaptopurine (6-MP), or azathioprine (AZA). Patients were randomized to the following treatment groups: REMICADE® 5 mg/kg IV (n=121), REMICADE® 10 mg/kg IV (n=122), or placebo (n=121). Infusions were administered at Weeks 0, 2, and 6, and every 8 weeks thereafter through Week 46.5
Final efficacy evaluations were completed 8 weeks following the last infusion. Concomitant treatment with stable doses of aminosalicylates, corticosteroids, and/or immunomodulators was permitted throughout the study. Of patients receiving steroids at baseline, tapering was allowed beginning at Week 8. The primary efficacy endpoint was clinical response at Week 8; secondary endpoints included clinical remission and mucosal healing.5
Note: The recommended dose of REMICADE® is 5 mg/kg given as an IV induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg IV every 8 weeks thereafter for the treatment of adult patients with moderately to severely active ulcerative colitis.1
The safety and efficacy of REMICADE® were evaluated in ACT 2 (N=364) (ACT=Active Ulcerative Colitis Trial), a randomized, double-blind, placebo-controlled, multicenter trial conducted in patients with moderately to severely active ulcerative colitis who had an inadequate response or were intolerant to conventional therapy. Patients presented with a Mayo score between 6 and 12, and an endoscopy subscore of ≥2. Prior failed or intolerable therapies in ACT 2 included oral corticosteroids, 6-mercaptopurine (6-MP), or azathioprine (AZA) and/or aminosalicylates. Patients were randomized to the following treatment groups: REMICADE® 5 mg/kg IV (n=121), REMICADE® 10 mg/kg IV (n=120), or placebo (n=123). Infusions were administered at Weeks 0, 2, and 6, and every 8 weeks thereafter through Week 22.5
Final efficacy evaluations were completed 8 weeks following the last infusion. Concomitant treatment with stable doses of aminosalicylates, corticosteroids, and/or immunomodulators was permitted throughout the study. Of patients receiving steroids at baseline, tapering was allowed beginning at Week 8. The primary efficacy endpoint was clinical response at Week 8; secondary endpoints included clinical remission and mucosal healing.5
Note: The recommended dose of REMICADE® is 5 mg/kg given as an IV induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg IV every 8 weeks thereafter for the treatment of adult patients with moderately to severely active ulcerative colitis.1
The REMICADE® Pediatric Ulcerative Colitis (UC) trial was a multicenter, phase 3, randomized, open-label, parallel-group trial to evaluate the safety and efficacy of REMICADE® in pediatric patients aged 6 to 17 years with moderately to severely active UC (N=60; Mayo score of 6 to 12; endoscopic subscore ≥2) and an inadequate response to conventional therapies. The primary objectives of the study were to evaluate clinical response after a 3-dose induction regimen of REMICADE® 5 mg/kg IV and the safety of REMICADE® during induction and maintenance regimens. Secondary objectives included the evaluation of 2 REMICADE® maintenance dosing regimens (every 8 weeks and every 12 weeks) in maintaining remission, as measured on the Pediatric Ulcerative Colitis Activity Index (PUCAI); the efficacy of a 3-dose regimen of REMICADE® in the induction of clinical remission, as measured by the Mayo score; and the induction of remission, as measured on the PUCAI.1,5
All patients received induction dosing of REMICADE® 5 mg/kg IV at Weeks 0, 2, and 6. Patients who did not respond to REMICADE® at Week 8 received no further REMICADE® and returned for safety follow-up. At Week 8, 45 patients were randomized to a maintenance regimen of REMICADE® 5 mg/kg IV given either every 8 weeks through Week 46 or every 12 weeks through Week 42.1,5
Note: REMICADE® 5 mg/kg IV every 12 weeks is not an FDA-approved maintenance dosing regimen for REMICADE® in the treatment of pediatric patients with moderately to severely active UC.1
EXPRESS evaluated 378 patients with moderate to severe plaque psoriasis. These patients had ≥10% body surface area (BSA) involvement, a Psoriasis Area and Severity Index (PASI) score of ≥12, and were candidates for systemic or phototherapy. Patients were randomized to placebo or REMICADE® (infliximab) at a dose of 5 mg/kg IV at Weeks 0, 2, and 6 (induction therapy), followed by maintenance therapy (5 mg/kg IV) every 8 weeks. At Week 24, the placebo group crossed over to REMICADE® induction (5 mg/kg IV), followed by maintenance therapy (5 mg/kg IV) every 8 weeks. Patients randomized to REMICADE® continued to receive REMICADE® 5 mg/kg IV every 8 weeks through Week 46. The primary endpoint was the proportion of patients achieving ≥75% improvement in PASI from baseline to Week 10.
EXPRESS II evaluated 835 patients with moderate to severe plaque psoriasis. These patients had ≥10% body surface area (BSA) involvement, a Psoriasis Area and Severity Index (PASI) score of ≥12, and were candidates for systemic therapy or phototherapy. Patients were randomized to placebo or REMICADE® (infliximab) at doses of 3 mg/kg IV or 5 mg/kg IV at Weeks 0, 2, and 6 (induction therapy). At Week 14, patients in the REMICADE® arms continued on their original dose but were randomized to either an every 8 week scheduled maintenance therapy or an as needed (PRN) maintenance therapy through Week 46. Patients randomized to the PRN maintenance therapy group received their original REMICADE® dose when baseline improvement in PASI was <75% and received placebo if PASI improvement was ≥75%. Maintenance visits occurred monthly. At Week 16, the placebo group crossed over to REMICADE® induction therapy (5 mg/kg IV), followed by a maintenance therapy every 8 weeks. The primary endpoint was proportion of patients achieving PASI 75 at Week 10.
SPIRIT evaluated 249 patients with plaque psoriasis. These patients had ≥10% body surface area (BSA) involvement, a Psoriasis Area and Severity Index (PASI) score of ≥12, and had previously received either psoralen plus ultraviolet A treatment (PUVA) or other systemic therapy for their psoriasis. Patients were randomized to either placebo or REMICADE® (infliximab) at doses of 3 mg/kg IV or 5 mg/kg IV at Weeks 0, 2, and 6 (induction therapy). At Week 26, patients with a static physician’s global assessment (sPGA) score of moderate or worse (≥3 on a scale of 0 to 5) received an additional dose of the randomized treatment. The primary endpoint was the proportion of patients achieving ≥75% improvement in PASI from baseline at Week 10.
ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy), a 24-week, multicenter, double-blind, placebo-controlled, randomized, phase 3 study in 279 adult patients with active ankylosing spondylitis according to the modified New York criteria for ≥3 months, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain assessment score ≥4 on a Visual Analog Scale (VAS), each on a scale of 0-10. The primary endpoint was the proportion of patients with a 20% improvement response according to the criteria of the ASAS International Working Group. Patients were randomized to 1 of 2 treatment groups in a 3:8 ratio: placebo (n=78) or REMICADE® 5 mg/kg (n=201) infused at Weeks 0, 2, 6, 12, and 18. Concurrent stable treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and tramadol was permitted during the study. Patients were not permitted to be on any disease-modifying antirheumatic drugs (DMARDs) or systemic corticosteroids.
IMPACT 2 (Induction and Maintenance Psoriatic Arthritis Clinical Trial 2): a randomized, double-blind, placebo-controlled, multicenter, phase 3, parallel-group study of REMICADE® in 200 adult patients with active PsA for at least 6 months who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients had active articular disease (≥5 swollen and tender joints each), psoriatic target skin lesion (≥2 cm in diameter), and either C-reactive protein (CRP) ≥1.5 mg/dL or morning stiffness lasting ≥45 minutes. Stable methotrexate (MTX) doses of ≤25 mg/week at study entry and stable oral corticosteroid doses equivalent to ≤10 mg/day of prednisone were permitted. During the 24-week, double-blind phase, patients received either REMICADE® 5 mg/kg IV (n=100) or placebo (n=100) at Weeks 0, 2, 6, 14, and 22. At Week 16, placebo patients with <10% improvement in swollen and tender joint counts were switched to active treatment and received REMICADE® 5 mg/kg IV at Weeks 16, 18, 22, 30, 38, and 46. At Week 24, all patients receiving placebo crossed over to active treatment and received REMICADE® 5 mg/kg IV (n=91) at Weeks 24, 26, 30, 38, and 46. Primary endpoints included the proportion of patients with ACR20 response at Week 14 and the change from baseline in total modified van der Heijde-Sharp (vdH-S) score at Week 24. Improvement in Psoriasis Area and Severity Index (PASI) was evaluated in psoriatic arthritis patients with baseline body surface area (BSA) ≥3% (n=87, placebo; n=83, REMICADE®).
START (Safety Trial for Rheumatoid Arthritis with REMICADE® Therapy): a 54-week, randomized, multicenter, double-blind, 3-arm, parallel-group, phase 3 study of the safety of REMICADE® in combination with methotrexate (MTX) in adult patients with moderately to severely active RA. Moderately to severely active RA was defined as ≥6 swollen (out of 66 total) and ≥6 tender joints (out of 68 total) for ≥3 months prior to screening. Patients were receiving MTX for ≥3 months before randomization and at a stable dose (≤25 mg/week) for ≥4 weeks before randomization. Patients could continue receiving other conventional disease-modifying antirheumatic drugs (DMARDs) as long as doses had been stable for ≥4 weeks. Doses of nonsteroidal anti-inflammatory drugs (NSAIDs) and oral corticosteroids must have been stable for ≥4 weeks prior to screening.
The primary objective was to assess the relative risk of serious infection within 22 weeks of initiating therapy with REMICADE® + MTX in subjects matching clinical practice demographics (including severity of disease, background DMARD use, and concomitant disease). Secondary objectives measured the safety and efficacy of dose-escalation regimens in patients with an incomplete response to the initial dose of REMICADE® 3 mg/kg every 8 weeks and the safety of REMICADE® + MTX after 1 year.
Patients (N=1084) were randomized in a 1:1:1 ratio to 1 of 3 treatment groups: placebo infusions through Week 14, followed by REMICADE® 3 mg/kg infusions every 8 weeks through Week 46 (Group 1, n=363); REMICADE® 3 mg/kg infusions every 8 weeks through Week 46, with dose escalation from Week 22 to 46 by 1.5 mg/kg increments, if the patient had an inadequate response (Group 2, n=360); and REMICADE® 10 mg/kg infusions every 8 weeks through Week 46 (Group 3, n=361). At Week 26, Group 2 and Group 3 patients received a placebo infusion in order to maintain treatment blind. The median dose of MTX was 15 mg/week.
ATTRACT (Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy): a 2-year, multicenter, double-blind, placebo-controlled, randomized, phase 3 study of REMICADE® with methotrexate (MTX) in 428 patients with moderately to severely active MTX-refractory established RA (MTX use ≥3 months). Moderately to severely active RA was defined as ≥6 swollen joints (out of 66 total) and ≥6 tender joints (out of 68 total) and ≥2 of the following:
Primary endpoints: reduction of signs and symptoms at 30 weeks, inhibition of structural damage at 54 weeks, and improvement in physical function at 102 weeks. Nearly 50% of patients had advanced disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids (≤10 mg/day) permitted at stable doses; no other disease-modifying antirheumatic drugs (DMARDs) allowed. There were 4 REMICADE® groups: 3 mg/kg IV q8 weeks + MTX (n=86), 3 mg/kg IV q4 weeks + MTX (n=86), 10 mg/kg IV q8 weeks + MTX (n=87), and 10 mg/kg IV q4 weeks + MTX (n=81); patients randomized to placebo + MTX (n=88).
ASPIRE (Active-controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset): a 54-week, multicenter, double-blind, active treatment-controlled, randomized, phase 3 study of REMICADE® with methotrexate (MTX) in 1004 MTX-naïve adult patients with moderately to severely active early RA (≥3 months and ≤3 years from date of diagnosis). Moderately to severely active RA was defined as ≥10 swollen joints (out of 66 total) and ≥12 tender joints (out of 68 total) and ≥1 of the following:
Concurrent stable treatment with corticosteroids (equivalent to ≤10 mg prednisone per day) and usual doses of nonsteroidal anti-inflammatory drugs (NSAIDs) were permitted. The coprimary endpoints were reduction of signs and symptoms, inhibition of structural damage, and improvement in physical function from baseline to Week 54. Patients were randomized into 1 of 3 treatment groups in a 5:5:4 ratio: REMICADE® 3 mg/kg IV + MTX (n=359), REMICADE® 6 mg/kg IV + MTX (n=363), and placebo + MTX (n=282). REMICADE® or placebo was infused at Weeks 0, 2, and 6, and every 8 weeks thereafter. MTX was started at 7.5 mg/week and gradually increased to 20 mg/week by Week 8. All patients were to maintain a target MTX dose of 20 mg/week for the duration of the trial, whenever possible.
Infusions every 8 weeks after 3 induction doses. REMICADE® is
administered by intravenous (IV) infusion over a period of not
less than
5 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
5 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
If response is lost, consider treatment with 10 mg/kg
IV1
Patients who do not respond by Week 14 are unlikely to
respond, and consideration should be given to discontinuing
REMICADE® in these patients1
Infusions every 8 weeks after 3 induction doses. REMICADE® is administered by intravenous (IV) infusion over a period of not less than 2 hours.1
5 mg/kg IV given at 0, 2, and 6 weeks
as
an induction regimen
5 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
Infusions every 8 weeks after 3 induction doses. REMICADE® is
administered by intravenous (IV) infusion over a period of not
less than
5 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
5 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
Infusions every 8 weeks after 3 induction doses. REMICADE® is
administered by intravenous (IV) infusion over a period of not
less than
5 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
5 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
Infusions every 8 weeks after 3 induction doses. REMICADE® is
administered by intravenous (IV) infusion over a period of not
less than
5 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
5 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
Infusions every 8 weeks after 3 induction doses. REMICADE® is
administered by intravenous (IV) infusion over a period of not
less than
3 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
3 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
REMICADE® should be given in combination with methotrexate.
For patients who have an incomplete response,
consideration may be given to adjusting the dose up to 10
mg/kg IV or treating as often as every 4 weeks, bearing in
mind that risk of serious infections is increased at higher
doses.
Infusions every 8 weeks after 3 induction doses. REMICADE® is
administered by intravenous (IV) infusion over a period of not
less than
5 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
5 mg/kg IV given every 8 weeks thereafter
as a maintenance regimen
REMICADE® can be used with or without methotrexate in active PsA.
Infusions every 6 weeks after 3 induction doses. REMICADE® is administered by intravenous (IV) infusion over a period of not less than 2 hours.1
5 mg/kg IV given at 0, 2, and 6 weeks
as an induction regimen
5 mg/kg IV given every 6 weeks thereafter
as a maintenance regimen
cp-129778v1
