Guide. Healthcare Professional Administration and Monitoring

Transcription

1 Healthcare Professional Administration and Monitoring Guide CIMZIA, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the response to disease-modifying antirheumatic drugs (DMARDs), including methotrexate, has been inadequate. CIMZIA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. CIMZIA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate.

2 CIMZIA CIMZIA for the treatment of rheumatoid arthritis (RA) is administered as a subcutaneous injection. This administration and monitoring guide provides information on the correct administration of CIMZIA and on the need for monitoring following treatment with CIMZIA. This CIMZIA administration and monitoring guide is one component of a set of educational tools available for CIMZIA : Patient Alert Card to be supplied to all patients treated with CIMZIA Patient Medication Guide to be supplied to all patients treated with CIMZIA Prescriber Guide to be supplied to all physicians prescribing CIMZIA Please contact the prescribing physician if you require any additional information on the safe administration of CIMZIA. After proper training in injection technique, patients may self-inject with CIMZIA if their physician determines that it is appropriate and with medical follow-up as necessary. A separate guide has been developed for patients that want to be trained in self-injection techniques. This guide is also designed to encourage appropriate self-injection and training techniques to patients and to advise patients on selfmonitoring for side effects and the appropriate action to be taken by the patient if these side effects arise. Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with significant morbidity and mortality. The disease is characterised by inflammation of the synovial joints, resulting in pain, swelling, and joint damage with secondary deformity and progressive disability, and chronic fatigue as well as impairment of patient physical function and health-related quality of life (HRQoL). Overview of CIMZIA CIMZIA is a recombinant, humanised antibody Fab fragment conjugated to polyethylene glycol (PEG). CIMZIA is a tumour necrosis factor alpha (TNFa) inhibitor with high affinity for human TNFa (a key pro-inflammatory cytokine with a central role in inflammatory processes). CIMZIA does not contain a fragment crystallisable (Fc) region, which is normally present in a complete antibody, and therefore does not fix complement or cause antibody-dependent cellmediated cytotoxicity in vitro. It does not induce apoptosis in vitro in human peripheral bloodderived monocytes or lymphocytes, or neutrophil degranulation. Indication for CIMZIA CIMZIA, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease-modifying antirheumatic drugs (DMARD) including MTX, has been inadequate. CIMZIA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. CIMZIA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with MTX. 2 3

3 Clinical Efficacy of CIMZIA CIMZIA was studied in 2367 patients with RA in controlled and open label trials for up to 57 months. The efficacy and safety of CIMZIA have been assessed in two randomised, placebo-controlled, double-blind trials in patients 18 years of age with active RA diagnosed according to American College of Rheumatology (ACR) criteria: RAPID 1 (52 week study), and RAPID 2 2 (24 week study). CIMZIA was administered subcutaneously in combination with oral MTX. Patients were required to have received MTX for a minimum of 6 months at a stable dose of at least 10 mg weekly for 2 months prior to inclusion in both trials. ACR Response A statistically significantly greater ACR 20 response was achieved from Week 1 in both clinical trials compared to placebo. ACR 50 response was statistically significantly greater from Week 2. Responses were maintained through Weeks 52 (RAPID 1) and 24 (RAPID 2). Of the 783 patients initially randomised to active treatment in RAPID 1, 508 completed 52 weeks of placebo-controlled treatment and entered the open-label extension study. Of these, 427 completed 2 years of openlabel follow-up and thus had a total exposure to CIMZIA of 148 weeks overall. The observed ACR20 response rate at this time point was 91%. Fatigue and Physical Function In RAPID 1 and RAPID 2: CIMZIA -treated patients reported significant improvements in physical function as assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI) as early as Week 1 through to the end of the study (Week 52, RAPID 1; Week 24, RAPID 2) compared to placebo. Improvements in physical function were maintained to at least 2 years in the open-label extension to RAPID 1. CIMZIA -treated patients reported significant improvements in tiredness (fatigue) as reported by the Fatigue Assessment Scale (FAS) as early as Week 1 through to the end of the study (Week 52, RAPID 1; Week 24, RAPID 2) compared to placebo. SF-36 In both clinical trials, CIMZIA -treated patients reported significantly greater improvements in the SF-36 Physical and Mental Component Summaries (PCS and MCS) and all domain scores indicating better health-related quality of life (HRQoL). Improvements in HRQoL were maintained to at least 2 years in the open-label extension to RAPID 1. Radiographic Response In RAPID 1, structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score (mtss) and its components, the erosion score and joint space narrowing (JSN) score, at Week 52, compared to baseline. CIMZIA patients demonstrated significantly less radiographic progression than patients receiving placebo at Week 24 and Week 52. In the placebo group, 52% of patients experienced no radiographic progression (mtss 0.0) at Week 52 compared to 69% in the CIMZIA 200 mg treatment group. Of the 783 patients initially randomised to active treatment in RAPID 1, 508 completed 52 weeks of placebo-controlled treatment and entered the open-label extension study. Sustained inhibition of progression of structural damage was demonstrated in a subset of 449 of these patients who completed at least 2 years of treatment with CIMZIA (RAPID 1 and open-label extension study) and had evaluable data at the 2-year time point. Productivity at Work and Home CIMZIA -treated patients reported statistically significant improvements in the Work Productivity Survey compared to placebo. CIMZIA Should Be Administered by Subcutaneous Injection CIMZIA must be administered subcutaneously. CIMZIA treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of RA. Patients should be given the Patient Alert Card. Contraindications for CIMZIA CIMZIA is contraindicated in: Patients with hypersensitivity to the active substance or to any of the excipients. Patients with active tuberculosis (TB) or other severe infections such as sepsis or opportunistic infections. Patients with moderate to severe heart failure (NHYA classes III/IV). Dose of CIMZIA The recommended starting dose of CIMZIA for adult patients with RA is 400 mg (as 2 injections of 200 mg each on one day) at weeks 0, 2 and 4. This is then followed by a maintenance dose of 200 mg every 2 weeks starting at week 6. MTX should be continued during treatment with CIMZIA where appropriate. Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment. How Is CIMZIA Supplied? CIMZIA is administered subcutaneously. CIMZIA is supplied as a prefilled syringe package. In each prefilled syringe package there are: 2 single-use, 1 ml prefilled glass syringe with a fixed 25 gauge needle, providing 200 mg (1 ml) of CIMZIA 2 alcohol swabs Each prefilled syringe contains 200 mg of CIMZIA. Each 200 mg dose requires 1 subcutaneous 1 ml injection. Each 400 mg dose requires 2 subcutaneous 1 ml injections. Pack size of 2 syringes and multipack containing 6 (3 packs of 2) syringes are available. Not all pack sizes may be marketed. 4 5

4 Storage of CIMZIA Refrigerate CIMZIA at 2 C to 8 C. Do not freeze CIMZIA. Do not use beyond the expiry date on container. The shelf-life for CIMZIA is 18 months. Keep the prefilled syringe in the outer carton in order to protect it from light. Keep the container out of the reach and sight of children Interaction With Other Medicinal Products Concomitant treatment with MTX, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics showed no effect on the pharmacokinetics of CIMZIA based on a population pharmacokinetics analysis. The combination of CIMZIA and anakarina or abatacept is not recommended. Before Injecting CIMZIA : Before administering CIMZIA you should contact the prescribing physician if the patient: Thinks they have an infection. Patients should not take CIMZIA if they have any kind of infection Is being treated for an infection Has signs of an infection, such as a fever, cough, or flu-like symptoms Has or has had hepatitis B Has any open cuts or sores on their body Gets a lot of infections or has infections that keep coming back Has HIV Has TB, or has been in close contact with someone with TB Was born in, lived in, or travelled to countries where there is more risk for getting TB Lives or has lived in certain parts of the world where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis) Has had any type of cancer Has heart failure. CIMZIA should not be used in patients with moderate to severe heart failure Has seizures, any numbness or tingling or a disease that affects their nervous system, such as multiple sclerosis Is scheduled to receive a vaccine Patients should not receive a live or attenuated vaccine while taking CIMZIA Is pregnant, planning to become pregnant, or breastfeeding CIMZIA has not been studied in pregnant or nursing women Is scheduled to undergo surgery or dental procedures A patient who requires surgery or dental procedures while on CIMZIA should be closely monitored for infections Is scheduled to undergo a coagulation assay CIMZIA may erroneously cause these tests to indicate prolonged clotting time when none exists Is allergic to any of the ingredients in CIMZIA Is taking Kineret (anakinra) or Orencia (abatacept) There may be a higher chance for serious infections when taking CIMZIA with these medications Do Not Use the CIMZIA Prefilled Syringe if: Any name other than CIMZIA is on the package and prefilled syringe label The expiry date on the container has passed (the expiry date refers to the last day of the month shown) The packaging is torn or if the tamper evident seals are missing or broken on the top and bottom of the carton when you receive it The prefilled syringe is frozen or has been left in direct sunlight The medicine in the prefilled syringe is not clear to pale yellow, or has large, coloured particles in it Preparing for Injection For each 200-mg injection, you will use: 1 prefilled syringe of CIMZIA with needle 1 alcohol swab CIMZIA may be injected into the patient s abdomen or thigh area. If administering more than one injection, each injection should be given at a different injection site, in the abdomen and thigh. Wash your hands thoroughly prior to injection. Take either 1 or 2 CIMZIA prefilled syringes and alcohol swabs out of the refrigerator for injection, depending on the prescribed dose. If there is still a prefilled syringe in the carton, put it back in the refrigerator right away. Let the medicine in the syringe come to room temperature before injection. This will take about 30 minutes. Do not try to warm up the syringe. Do not shake the prefilled syringe prior to use. Choosing and Preparing Injection Site Choose a different site on the abdomen and/or thigh each time. Never inject into areas where the skin is tender, bruised, red, or hard or where the patient has scars or stretch marks. Be sure to alternate the injection site between the patient s thighs and abdomen to avoid infection. You may find it helpful to keep notes of the patient s previous injection sites. Once the injection site has been selected, use an alcohol swab to wipe the site and the area around it. Be sure not to touch this area again until you re ready to inject. 6 7

5 Injecting Remove the needle cover by pulling straight up on the plastic ring. Take care not to touch the needle and do not allow the needle to touch any surface. Place the needle cover to the side. Hold the syringe so the needle is pointing up and lightly tap the syringe to force any air bubbles to the top. Press the plunger slowly until you expel any air. Stop when a small drop appears at the tip of the needle. With one hand, hold the syringe with the needle facing down; take care not to touch the needle with your fingers or allow it to touch any surface. With the other hand, gently pinch a fold of the patient s cleaned skin and insert the needle subcutaneously at about a 45-degree angle, with a one quick, short motion. Push the plunger to inject the solution. It can take up to 10 seconds to empty the syringe. When the syringe is empty, carefully remove the needle from the skin at the same angle at which it was inserted. Release the skin with the first hand. Press the clean cotton ball or gauze pad over the injection site for a few seconds. Instruct the patient not to rub the injection site. You may cover the injection site with small adhesive bandage if necessary. DO NOT re-use the syringe or re-cap the needle. Throw away the used prefilled syringe and needle in a special puncture-proof container. Disposing of Needles and Syringes Needles and syringes should be disposed of in a puncture-proof container ( sharps container). When the container is about two-thirds full, tape the lid closed. Dispose of the container in line with local requirements. Do not throw away the container in the trash or recycle. Unused Product or Waste Material Any unused product or waste material should be disposed of in line with local requirements. Failed Injection If the injection mechanism fails contact UCB Medical Information. Administration Errors Any administration errors with CIMZIA should be reported to the treating physician and the local representative of the Marketing Authorisation Holder (see the Summary of Product Characteristics for more information) or to the Pharmacovigilance Department of the Health Authority. Spillage If you spill any product during the injection please advise the treating physician and contact UCB Medical Information. Missed Dose If a patient misses a dose of CIMZIA they should receive the next dose as soon as they remember and then continue injecting subsequent doses every 2 weeks as originally instructed. Self-Administration by Patients After proper training in injection technique, patients may self-inject with CIMZIA if their physician determines that it is appropriate and with medical follow-up as necessary. A separate guide has been developed for patients that want to be trained in self-injection techniques. Injection Site Reactions In the placebo-controlled RA clinical trials, 6.4% of patients treated with CIMZIA developed injection site reactions (erythema, itching, haematoma, pain, swelling or bruising), compared to 6.5% of patients receiving placebo. Injection site pain was observed in 1.5% of patients treated with CIMZIA with no cases leading to withdrawal. Side Effects During or Shortly After Administration of CIMZIA Severe hypersensitivity reactions (including acute injection-related and delayed systemic hypersensitivity reactions) have been reported rarely following CIMZIA administration in trials. If severe reactions occur, administration of CIMZIA should be discontinued immediately and appropriate therapy instituted. There are limited data on the use of CIMZIA in patients who have experienced a severe hypersensitivity reaction towards another TNF antagonist; in these patients caution is needed. Monitoring of Patients and Important Safety Information About CIMZIA As with all anti-tnfs there are some potential undesirable effects with CIMZIA. It is therefore important that patients are monitored following the administration of CIMZIA in order to optimise the use of CIMZIA. For a full list of the undesirable effects with CIMZIA please refer to the Summary of Product Characteristics. In patients who will be self-injecting CIMZIA, this guide should be used to educate the patient on the need to self-monitor for side effects. The patient should be referred to the Patient Medication Guide for more information. 8 9

6 Risk of Serious Infections Serious infections (bacterial, viral and fungal), including sepsis, and TB (including miliary, disseminated and extrapulmonary disease), and opportunistic infections (e.g. histoplasmosis, nocardia, candidiasis) have been reported in patients receiving TNF antagonists including CIMZIA. In the placebo-controlled clinical trials, there were more new cases of serious infection in the CIMZIA treatment groups (0.06 per patient-year; all doses), compared with placebo (0.02 per patient-year). Some of these events have been fatal. Patients should be monitored closely for new serious infections including TB during and up to 5 months after treatment with CIMZIA, taking into account the long half-life of the product. The possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy should be considered. If active tuberculosis is diagnosed prior or during treatment, CIMZIA therapy must not be initiated or must be discontinued. Patients should be instructed to seek medical advice if signs/symptoms suggestive of TB occur during or after therapy with CIMZIA. These include: Recent or ongoing infections Previous or current history of respiratory system problems Night sweats or any other systemic features of TB Wasting/weight loss Patients should be instructed to seek medical advice in the following circumstances: Family or other contact history of persons with TB Vaccination history for TB Positive PPD test Recent foreign travel In case of serious infection or sepsis the treating physician should be contacted, who will consider discontinuation of CIMZIA. Hepatitis B Reactivation TNF inhibitors, including CIMZIA have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Patients should contact their doctor immediately if they experience any of the following symptoms: Feel unwell Poor appetite Tiredness Fever Skin rash Joint pain Malignancies (Including Lymphoma and Leukaemia) The potential role of TNF antagonist therapy in the development of malignancies is not known. In clinical trials with CIMZIA and other TNF antagonists, more cases of lymphoma and other malignancies have been reported among patients receiving TNF antagonists than in control patients receiving placebo. Furthermore, there is an increased background lymphoma risk in RA patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. Patients should be monitored for symptoms of lymphoma including: Swollen lymph nodes in the neck, underarms, groin, or other areas Excessive sweating, especially while sleeping at night Fever Severe itchiness Unintentional weight loss In an exploratory clinical trial evaluating the use of another TNF antagonist, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients. All patients had a history of heavy smoking. Therefore, caution should be exercised when using any TNF antagonist in COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. Patients should contact their doctor immediately if they experience any symptoms suggestive of malignancy. Congestive Heart Failure Worsening congestive heart failure (CHF) has been observed with TNF-blocking agents, including CIMZIA, and new onset CHF has been reported with TNF-blocking agents. Patients should be monitored for symptoms of CHF including: Cough Shortness of breath Swelling of feet and ankles Weight gain Patients should contact their doctor immediately if they experience any symptoms suggestive of CHF. Neurological Events TNF-blocking agents, including CIMZIA, have been associated in rare cases with new onset or exacerbation of demyelinating disease. Patients should be monitored for symptoms of demyelinating disease, especially multiple sclerosis including: Dizziness Numbness or tingling Problems with vision Weakness in the arms and legs Patients should contact their doctor immediately if they experience any of these symptoms

7 Haematological Reactions The development or worsening of cytopaenias has been reported with CIMZIA. Patients should be monitored for symptoms of cytopaenia. Patients should contact their doctor immediately if they experience any symptoms associated with blood problems including: Fever that doesn t go away easily Bruising very easily Bleeding very easily Looking very pale Auto-immunity, Lupus and Lupus-like Illness Treatment with CIMZIA may result in the formation of autoantibodies and, uncommonly, in development of a lupus-like syndrome (an auto-immune disease). Patients should contact their doctor immediately if they experience any symptoms associated with lupus-like syndrome including: Shortness of breath Joint pain Rash on the cheeks and arms that worsens with sun exposure Hypersensitivity Severe hypersensitivity reactions have been reported rarely following CIMZIA administration in trials. If severe reactions occur contact the treating physician immediately. Administration of CIMZIA should be discontinued immediately and appropriate therapy instituted. Please refer to the Summary of Product Characteristics for a full list of Undesirable Effects and for further information about CIMZIA. REFERENCES: 1. Keystone E, van der Heijde D, Mason D Jr, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008;58: Smolen J, Landewé RB, Mease P, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis. 2009;68: OXO, Good Grips and the associated logos are registered trademarks of Helen of Troy Limited and are used under license. CIMZIA is a registered trademark of UCB PHARMA, S.A. or its affiliates UCB Pharma, S.A., Belgium. All rights reserved. CZP-PRM CIMZIA, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the response to disease-modifying antirheumatic drugs (DMARDs), including methotrexate, has been inadequate. CIMZIA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. CIMZIA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate.