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Actemra and prednisone. Actemra Cuts Steroid Needs Even in Nonresponders |
Executive Summary - Clinical Review Report: Tocilizumab (Actemra) - NCBI Bookshelf - Publication types
Barbara Brody. People with moderate-to-severe rheumatoid arthritis RA often need to take a biologic drug as well as a glucocorticoid in order to get their disease activity under control.
Can people with RA taking the biologic drug tocilizumab Actemra and the glucocorticoid prednisone safely ditch the prednisone once they meet the criteria for low disease activity? The study, a randomized, controlled trial, followed patients who had reached remission or low disease activity while taking a combination of Actemra and prednisone.
Over the course of 24 weeks, one group of patients continued both drugs while the other slowly tapered off prednisone until they were no longer using it. The authors concluded that sticking with prednisone provided better disease activity control compared to tapering off it, but that the overall difference in disease activity scores DASESR in both the taper and non-taper groups was similar. All drugs, including Actemra — an interleukin 6 IL-6 inhibitor — have side effects, but patients tend to especially dislike taking gluticorticoids like prednisone.
Glucocorticoids are a type of steroid medication, and they often cause bothersome side effects including weight gain, acne, dizziness, and insomnia, as well as raise the risk of longer-term health problems like osteoporosis and diabetes.
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❿Actemra Cuts Steroid Needs Even in Nonresponders | MedPage Today.
Study record managers: refer to the Data Element Definitions if submitting registration or results information. This is a single center, open label study that will assess the efficacy and safety of 52 weeks of tocilizumab TCZ in combination with 8-weeks of prednisone in 30 patients with active giant cell arteritis GCA.
The primary endpoint of the study, sustained remission, will be assessed at week The definition of sustained remission contains 3 elements:. Prednisone taper over 8 weeks with a starting dose between 20 and 60 mg. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Diagnosis of GCA classified per the following criteria:. Inability, in the opinion of the investigator, to withdraw GC treatment through protocol-defined taper regimen due to suspected or established adrenal insufficiency. We're building a better ClinicalTrials. Check it out and tell us what you think!
Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information. Search for terms. Save this study. Warning You have reached the maximum number of saved studies Tocilizumab Plus a Short Prednisone Taper for GCA The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Listing a study does not mean it has been evaluated by the U. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Last Update Posted : July 26, See Contacts and Locations.
View this study on Beta. Study Description. This is an open-label pilot study of tocilizumab TCZ mg weekly administered subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone. Detailed Description:.
Completion of the pre-specified prednisone taper protocol Absence of disease flare relapse since the induction of remission by week 8. Drug Information available for: Prednisone Tocilizumab.
FDA Resources. Arms and Interventions. Tocilizumab is an interleukin-6 IL-6 receptor inhibitor. Outcome Measures. Primary Outcome Measures : Sustained remission [ Time Frame: 52 weeks ] Proportion of patients in sustained remission by week Number, nature and severity of adverse events by week Number and nature of serious adverse events by week Eligibility Criteria.
Information from the National Library of Medicine Choosing to participate in a study is an important personal decision.
Patients on methotrexate at screening will require discontinuation of this agent prior to baseline visit. Patients should be screened for latent TB and, if positive, treated according to local practice guidelines prior to initiating TCZ treatment. Patients treated for LTBI within 3 years are eligible.
Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials.
More Information. GCA Tocilizumab Prednisone. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Giant Cell Arteritis. Drug: Tocilizumab Drug: Prednisone. Phase 4. Study Type :. Interventional Clinical Trial. Estimated Enrollment :. Actual Study Start Date :. Estimated Primary Completion Date :. Estimated Study Completion Date :.
Experimental: Tocilizumab and prednisone TCZ mg administered by subcutaneous injection weekly for 52 weeks. Contact: Ana D Fernandes October 31, Key Record Dates.
❾-50%}Actemra and prednisone
Het medicijn waarmee de belangrijkste wisselwerkingen optreedt, is:Mag ik dit medicijn gebruiken als ik zwanger ben, wil worden of borstvoeding geef. U kunt dit middel veilig gebruiken. Het wordt al jarenlang gebruikt door zwangere vrouwen en vrouwen die borstvoeding geven, zonder nadelige gevolgen voor het kind.
Gebruikt u medicijnen op met of die u zonder die koopt. Wilt u helpen om de kennis over medicijngebruik tijdens zwangerschap en borstvoeding te vergroten.
Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. View in own window. Giant cell arteritis GCA is a systemic large-vessel vasculitis found almost exclusively in patients aged 50 years and older.
Symptoms typically resolve rapidly in response to corticosteroid therapy and if the patient is free of symptoms and abnormal laboratory parameters, the corticosteroid dose can be tapered gradually over the course of one to two years.
The long-term use of oral corticosteroid therapy introduces a host of adverse effects and increases the risk of bone fractures, worsening of diabetes and hypertension, thrombotic events, gastrointestinal bleeding, muscle weakness from myopathy, glaucoma, and cataracts.
Tocilizumab is an anti-human interleukin-6 IL-6 receptor monoclonal antibody that binds to and inhibits signalling through both soluble and membrane-bound IL-6 receptors. Tocilizumab is also approved in Canada for patients with polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis. Patients enrolled were either newly diagnosed or had relapsing disease and were receiving treatment with 20 mg to 60 mg of prednisone daily.
Patients were randomized to tocilizumab mg SC weekly or every other week both with a week prednisone taperplacebo with week prednisone taper, or placebo with week prednisone taper. Patients who experienced a disease flare or could not adhere to the taper due to ongoing disease activity stopped the protocol-defined tapering schedule and could receive escape prednisone.
A patient could have symptoms of GCA or elevated ESR and still be considered in remission if the investigator determined these symptoms were not severe enough to be classified as a disease flare.
Sustained remission the primary end point was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained from week 12 up to week The primary outcome analysis compared the proportion of patients in sustained remission at week 52 for each tocilizumab group versus the placebo plus week prednisone taper group. The key secondary outcome assessed noninferiority of each tocilizumab group versus the placebo plus week taper for the proportion of patients in sustained remission.
The GiACTA study was not adequately powered or of sufficient duration to evaluate longer-term GCA - and prednisone-related morbidities such as fractures and cardiovascular events, which are important to patients. Moreover, the available evidence was limited to a single RCT with a relatively small number of patients per treatment group 50 or For both tocilizumab dosage groups, the lower bound of the Similar results were observed in the analysis of patients who completed the study and were compliant with treatment.
Sensitivity analyses for the primary outcome suggested that the findings were generally robust. These data suggested no notable differences in sustained remission rate with tocilizumab versus placebo for relapsing GCA patients versus new-onset patients, although the data were limited by small sample sizes and no between-group comparisons or treatment-by-disease status interaction P values were reported. The median cumulative prednisone dose over the week blinded treatment period which included scheduled taper doses and all escape or commercial prednisone doses was 1, mg in both tocilizumab groups, 3, mg in the placebo plus week taper group, and 3, mg in the placebo plus week taper group.
The time-to-first-flare data suggested that flare may be delayed with weekly tocilizumab versus both placebo groups and for biweekly tocilizumab versus the placebo plus week taper group, with hazard ratios ranging from 0. However, the cumulative prednisone dose and time to first flare were secondary outcomes that were outside the statistical testing hierarchy and should be interpreted as exploratory.
However, the trial was not powered for patient-reported outcomes and the instruments used may not be responsive to change in GCA patients. The results were potentially biased due to the exclusion of post-escape data as these data were not missing at random and their exclusion may have violated the assumptions of the repeated measures model, although a post hoc analysis that included post-escape data yielded similar results.
All patient-reported outcomes were outside the statistical testing hierarchy and were limited by the extent of missing data. In terms of GCA -related morbidity, there were no new cases of permanent vision loss during the study. Most patients in all of the groups displayed signs and symptoms of GCA during the trial, though they did not always signal a disease flare. According to the clinical expert consulted for this review, the differences in sustained remission rate and prednisone exposure seen with tocilizumab treatment as compared with placebo with week or week prednisone taper were clinically meaningful.
However, it is unclear if the reductions in prednisone doses are generalizable, as corticosteroid tapering does not follow a standardized regimen in clinical practice.
Moreover it is unknown if the treatment effects will result in longer-term reductions in GCA -related morbidity such as stroke or corticosteroid-related morbidity such as fractures, diabetes, cardiovascular events, and cataractsas the trial was not powered, or of sufficient duration, to detect differences in these outcomes. Of note, the trial duration was limited to 52 weeks, and thus does not provide information on longer-term adverse events, although the safety profile of tocilizumab is generally known, as the drug is approved in Canada for rheumatoid arthritis and juvenile idiopathic arthritis.
According to the clinical expert consulted for this review, the first objective of the treatment of GCA is to control the signs and symptoms of the disease and to prevent complications such as visual loss and stroke. The second objective is to taper steroids to prevent the morbidities of chronic high- and moderate-dose steroids. There is no established protocol for steroid tapering. Methotrexate has not met the challenge. Tocilizumab is the first breakthrough in the treatment of GCA.
The data further support the hypothesis that tocilizumab treats the fundamental disease process. Total proof of the latter, the ability to avoid corticosteroids completely, will require a separate study. Moreover, evidence that tocilizumab can reduce longer-term GCA- or corticosteroid-related morbidity is lacking.
The clinical expert indicated that the methods of diagnosing a patient with GCA may be variable across centres due to the availability and access to diagnostic tools such as magnetic resonance angiography MRAcomputed tomography angiography CTAor positron emission scanning PET scanning. In the real world, obtaining such confirmation is problematic.
Access to temporal artery biopsy is not often timely and not all patients will be biopsy-positive. PET scanning is not available in most centres. MRA and CTA provide important diagnostic information, but timely access varies across Canada and making them an absolute requirement for trial entry adds substantial costs. Further, the sensitivity and specificity of imaging is not established. In addition, still to be established is the utility of imaging to confirm the definition of remission and the duration of therapy.
In the absence of biopsy and imaging information, the clinician depends on the clinical presentation and the presence of elevated acute-phase reactants. Thus, physician judgment that the patient has GCA, supported as much as possible by confirmatory tests, is the current standard of care. Any reimbursement criteria that includes an absolute requirement for a confirmatory test would limit access to those in need. A dedicated register of all Canadian patients treated with tocilizumab would be invaluable in answering important aspects of safety.
One trial, which evaluated the use of tocilizumab SC versus placebo in patients with active GCAmet the inclusion criteria for the systematic review. Statistically significantly more patients who received tocilizumab weekly or biweekly in combination with a week prednisone tapering regimen achieved sustained remission at 52 weeks than those on placebo.
Data on the cumulative prednisone dose and time to first flare also favoured tocilizumab versus placebo, although these outcomes should be interpreted as exploratory. The treatment effects observed were clinically important, but it is unclear if these benefits will result in longer-term reductions in GCA- or corticosteroid-related morbidity or mortality, which are important to patients. Few clinically important differences between tocilizumab and placebo in health-related quality of life were detected.
However, the study was not powered for these measures and the instruments used may not be responsive in patients with GCA. These analyses may also be biased due to the exclusion of data from patients who required escape prednisone therapy, and due to the extent of missing data.
The available evidence was limited to a single RCT with a relatively small number of patients per treatment group and treatment duration of 52 weeks. Missing doses during the taper were assumed to be the minimum-dose tablets from that pack.
Patients who received an increased dose of prednisone because they entered escape therapy were included in their originally assigned treatment group. There was no imputation of missing data. Source: Clinical Study Report. This information is based on information provided in draft form by the clinical expert consulted by CDR reviewers for the purpose of this review. The copyright and other intellectual property rights in this document are owned by CADTH and its licensors.
These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors. Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.
Turn recording back on. Help Accessibility Careers. Search term. Executive Summary. Introduction Giant cell arteritis GCA is a systemic large-vessel vasculitis found almost exclusively in patients aged 50 years and older. Potential Place in Therapy a According to the clinical expert consulted for this review, the first objective of the treatment of GCA is to control the signs and symptoms of the disease and to prevent complications such as visual loss and stroke.
Conclusions One trial, which evaluated the use of tocilizumab SC versus placebo in patients with active GCAmet the inclusion criteria for the systematic review. Infections were the most frequently reported adverse event in all treatment groups. In this Page.
Introduction Results and Interpretation. Other titles in this collection. Recent Activity. Clear Turn Off Turn On. Follow NCBI. Tocilizumab Actemra. For the treatment of giant cell arteritis GCA in adult patients. As per indication. Tocilizumab doses of mg administered via subcutaneous injection weekly plus week prednisone tapering. October 27, Hoffmann-La Roche Limited.
Comparing Actemra vs Prednisone ; A total of drugs are known to interact with Actemra: 48 major drug interactions ( brand and generic names); moderate. Tocilizumab plus prednisone was linked to a sixfold reduced risk for linked with failure to respond to tocilizumab (Actemra, Genentech). Comparing Actemra vs Prednisone ; A total of drugs are known to interact with Actemra: 48 major drug interactions ( brand and generic names); moderate. Treatment options for GCA are limited and guidelines state that therapy with prednisone or prednisolone should be initiated immediately upon suspicion of. No interactions were found between Actemra and prednisone. However, this does not necessarily mean no interactions exist. Always consult your healthcare. The primary endpoint of the study, sustained remission, will be assessed at weekTocilizumab Actemra may have positive effects in patients not showing clinical responses by allowing reductions in corticosteroids doses, according to a five-center French study appearing online in Rheumatology. The open, observational, retrospective study evaluated patients with rheumatoid arthritis Patients were started on tocilizumab from December to June Mean RA duration in the cohort was With corticosteroid doses noted at enrollment and at weeks four, eight, 12, and 24, the researchers analyzed changes in disease activity to identify factors associated with corticosteroids dose alteration.
Over a mean follow-up period of Mean disease activity scores decreased from 5. A total of 19 patients stopped treatment owing, variously, to side effects, treatment failure, pregnancy or surgery. By week 24, Corticosteroids were withdrawn completely in one patient at week four, three patients at week eight, eight patients at week 12, and 15 patients at week And it is possible that in patients treated with high-dose corticosteroids, the clinician's main objective is to reduce dosage rather than RA activity, the authors noted.
At week 24, there was a nonsignificant trend toward a greater reduction in corticosteroids dose in nonresponders to tocilizumab treatment than responders, with a mean decrease of 6. With initial corticosteroids doses higher in nonresponders, the authors suggested that patients on high initial doses likely had more severe disease that was less amenable to treatment. Given the significant corticosteroids sparing during the first months of treatment, even in nonresponders, the authors proposed that tocilizumab could have an important benefit despite the absence of clinical response as conventionally judged.
Addressing limitations, they noted the open observational design and the absence of a comparator, both inherent to real-life studies. Other limitations were the retrospective collection of data, even with the use of standardized case report forms, and the limited follow-up time. Diana Swift is a freelance medical journalist based in Toronto.
Source Reference: Fortunet C, et al "Tocilizumab induces corticosteroid sparing in rheumatoid arthritis patients in clinical practice" Rheumatology ; DOI: Share on Facebook.
Opens in a new tab or window. Share on Twitter. Share on LinkedIn. Disclosures This study received no funding.
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