274. CLINICAL OUTCOMES OF PATIENTS WITH GIANT CELL ARTERITIS TREATED WITH TOCILIZUMAB IN REAL-WORLD CLINICAL PRACTICE
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Background: The GiACTA study demonstrated the superiority of subcutaneous tocilizumab (TCZ) plus prednisone vs prednisone alone in achieving sustained glucocorticoid (GC)-free remission in patients with giant cell arteritis (GCA) 1.We aimed to evaluate the effectiveness and safety of subcutaneous and intravenous TCZ in real-world clinical practice.Methods: We performed a retrospective analysis of GCA patients treated with TCZ at a single center (MGH) between 2010-2018.Time to disease relapse, number of relapses, prednisone use, and adverse events (AE) before and after TCZ initiation were assessed.Disease relapse was defined as the re-appearance of clinical manifestations of GCA (e.g., cranial symptoms) that required treatment modification.Results: A total of 60 GCA patients were included in the analysis (mean [SD] age of 69.3 [9.4] years; 71.7% female).The median (IQR) disease duration before TCZ use was 0.6 (0.2-1.6) years.Fifty-eight patients (96.7%) received concomitant prednisone (mean [SD] dose: 30 [18.3] mg daily) at the time of TCZ initiation.Patients received TCZ for a median (IQR) period of 0.5 (0.3-1.4) years.While not on TCZ treatment, 43 patients (71.7%) had 51 relapse (median [IQR] time to relapse 0.5 [0.3-0.7]years).On TCZ, 18 patients (30.0%) had 51 relapse (median [IQR] time to relapse 2.1 [0.6-2.6]years) (Table 1).Time to relapse was significantly longer after TCZ initiation than before TCZ (HR ¼ 0.22; 95% CI: 0.10 to 0.50; P ¼ 0.0003).Twenty-seven patients (46.6%) successfully tapered off prednisone during TCZ treatment.The incidence of AEs and serious AEs (SAE) was similar before and after TCZ initiation (Table 1).During TCZ treatment, however, 38 out of 81 AEs were considered related or possibly related to prednisone.An AE led to TCZ discontinuation in 5 patients.No deaths occurred during the study period. Conclusion:In this retrospective analysis, TCZ improved clinical outcomes in patients with GCA as indicated by a reduction in the incidence of relapses and by the ability to discontinue prednisone.The occurrence of AEs and SAEs (many due to GC) did not differ substantially while patients were on or off TCZ.These real-world findings support the previously reported efficacy and safety profile of TCZ in patients with GCA.Keywords:
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Introduction: Based on the known relevance of IL-6 in juvenile idiopathic arthritis (JIA) pathophysiology, tocilizumab has been investigated and approved for use in the treatment of systemic and polyarticular JIA. Tocilizumab is a humanized monoclonal antibody that inhibits signaling through both membrane bound and soluble IL-6R.Areas Covered: The purpose of this article is to summarize the available clinical data on the efficacy and safety of tocilizumab in JIA and to provide our opinion on the place of tocilizumab in current treatment regimens. A literature search for all relevant clinical trials and studies with regards to tocilizumab, JIA and IL-6 was performed through PubMed, in addition to a review of recent conference abstracts.Expert Opinion: Tocilizumab has an important and evolving role in controlling disease activity in patients with JIA. It has proven useful even in patients whose JIA has previously been refractory to other biologic disease modifying anti-rheumatic drugs (DMARDs) and also appears quite effective as monotherapy. Tocilizumab is relatively well tolerated amongst JIA patients, with systemic JIA patients experiencing more serious adverse events overall.
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Abstract: Giant cell arteritis (GCA) remains a medical emergency due to the threat of permanent sight loss. High-dose glucocorticoids (GCs) are effective in inducing remission in the majority of patients, however, relapses are common which lengthen GC therapy. GC toxicity remains a major morbidity in this group of patients, and conventional steroid-sparing therapies have not yet shown enough of a clinical benefit to change the standard of care. As the understanding of the underlying immunopathophysiology of GCA has increased, positive clinical observations have been made with the use of IL-6 receptor inhibitor therapies, such as tocilizumab (TCZ). This has led to prospective randomized control trials that have highlighted the safety and efficacy of TCZ in both new-onset and relapsing GCA. Keywords: giant cell arteritis, temporal arteritis, Horton disease, interleukin-6, tocilizumab, treatment
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The standard of care for patients with giant cell arteritis (GCA) is steroid therapy. However, prolonged courses of steroids often are required, leading to substantial steroid-associated complications. Until now, steroid-sparing immunosuppressive therapies have not been convincingly effective, but case series have suggested that the interleukin-6 receptor antagonist tocilizumab (Actemra) effectively treats patients with GCA.
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Background
Giant cell arteritis (GCA) is a vasculitis of large and medium sized arteries affecting people older than 50 years. Glucocorticosteroids (GC) are the mainstay of therapy but relapses are common, resulting in prolonged treatment course and adverse events. IL-6 correlates with disease activity of GCA and temporal artery biopsy samples show enhanced IL-6 production. Cases series and open label studies reported the efficacy of tocilizumab (TCZ) on symptoms and inflamamtory markers in GCA.Objectives
To report the French experience on the efficacy and safety of TCZ in patients with GCA and the evolution after treatment withdrawal.Methods
A retrospective multicenter study on patients treated with TCZ for their GCA was conducted. Treatment efficacy was evaluated at a clinical and biological level. Side effects and evolution after treatment withdrawal were also recorded.Results
Thirty-four patients (27 women and 7 males) aged 70.5±8.2 (mean±SD) were included. Diagnosis of GCA was based on the ACR criteria (30 patients) and/or on imaging abnormalities suggestive of GCA (8 patients). Giant cell disease was treated by GC and another immunosuppressant was added before TCZ introduction in 20/34 patients. Tocilizumab (8 mg/kg monthly) was introduced after a mean disease evolution of 18 months (0–107). It was efficient in all but 6 patients who still had mild symptoms while CRP was reduced from 40.4 mg/L to 1.5 mg/L (p<0,0001) and GC were tapered from 26.3 to 10.3 mg/day (p<0.0001). One patient died from a septic shock and 3 patients had to stop TCZ for adverse events. Among the 23 patients who stopped treatment (planned medical decision in 20 cases and side effects in 3 cases) eight patients experienced relapses that occurred after a mean of 3.5±1.3 months.Conclusions
TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA. However, side effects should be kept in mind in this population. Questions remain regarding the suspensive nature of this treatment and this should be specifically studied in future studies.Disclosure of Interest
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Abstract Background/Aims Giant cell arteritis (GCA) has been revolutionised by fast track pathways that ensure early secure diagnosis. The GiACTA study provided evidence for the beneficial role of tocilizumab in the treatment of GCA and encouraged us all to reconsider the role of corticosteroids. These data relate to real life experience of the use of tocilizumab, including current status of patients after completing the initial year of treatment. In Scotland, tocilizumab was initially used for patients with relapsing disease or steroid complications. However, since 2018, the Scottish Medicines Consortium has supported use from disease onset and it has become increasingly common to consider adding at diagnosis. Methods The case notes of 23 patients treated with tocilizumab were reviewed back to 2017. Patient demographics were collated including whether cranial (C) or large vessel vasculitis (LVV) variant. The diagnosis of GCA had to be confirmed by biopsy or imaging with GCA rheumatology clinic review. Any patients who discontinued tocilizumab prior to completing one year had the reason recorded. Duration on tocilizumab was intended to be one year. Data were reviewed to capture outcomes after treatment was withdrawn. Results 2 patients with non-relapsing disease discontinued tocilizumab within the first month due to early relative neutropenia (1.4). 5 of 21 patients who completed treatment have since had additional tocilizumab treatment. 1 patient with particularly severe relapsing disease and steroid complications remains on long term tapered tocilizumab monotherapy without attempt to stop (C and LVV). 4 patients (LVV=C) flared within 1-9 months (median 6 months) and resumed with steroids and subsequent tapers; all had commenced for relapsing disease. 1 patient (C), commenced on tocilizumab at diagnosis, opted for MTX when flared. 15 remaining patients are on no steroid, methotrexate or tocilizumab and are free of disease activity as yet, but undergoing monitoring for flare (12C 3 LVV variant). Conclusion Tocilizumab is effective, limits steroid exposure and is well-tolerated by patients. The most common reason for discontinuing tocilizumab was relative neutropenia (neutrophils 1-1.4). The majority of patients discontinued tocilizumab and have not yet flared off all treatment. Cranial variant was less associated with relapse after tocilizumab treatment versus LVV. New diagnoses appear less prone to relapse off tocilizumab than patients already known to have relapsing disease prior to using tocilizumab. Patients discontinuing tocilizumab benefit from ongoing monitoring to recognise the early stages of returning disease; this would need to be provided for at least one year. Patients discontinuing treatment, their GPs and carers need advice on routes to escalate concerns about returning symptoms. Fast track services need to provide a flare service in addition to a diagnosis pathway if there is to be safety, confidence and expert support for this patient group and primary care colleagues. Disclosure L.M.M. Hutton: Other; 2022 Roche educational grant to attend BSR.
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Giant cell arteritis is a systemic vasculitis of large vessels, manifesting mainly as temporal arteritis or large vessel vasculitis of the aorta and its branches. Glucocorticoid therapy is essential and so far had to be continued over a period of 1.5–2 years, resulting in relevant morbidity through adverse effects. With the approval of tocilizumab, an effective glucocorticoid sparing option is now available. In two randomized controlled trials, a profound reduction of cumulative glucocorticoid dose, prolonged relapse-free remission and reduced number of adverse events in the treatment groups have been demonstrated. Therefore, tocilizumab constitutes a novel therapeutic option in giant cell arteritis. Its differential role in different subgroups, timing of tocilizumab therapy and optimal treatment duration remain to be determined.
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Results Forty-two SJIA patients, 131 blood samplings were included in this study. Seventeen patients (40%) were treated with tocilizumab during the study. Serum IL-6 levels in patients without tocilizumab treatment significantly elevated in active disease with systemic features and arthritis [median (IQR) = 101.8 (303.2) pg/mL] when compared to active disease with only arthritis [median (IQR) = 4.5 (23) pg/mL], and remission on medication [median (IQR) = 1.5 (0.55) pg/mL], whereas serum IL-6 levels in patients with tocilizumab treatment were not different between groups but there were significantly different when compared to healthy children (p < 0.05). In addition, the correlation between serum IL-6 levels and JADAS-71 in patients without tocilizumab treatment (r = 0.71, p < 0.001) was stronger than patients with tocilizumab treatment (r = 0.42, p = 0.01). Serum sIL-6R levels in SJIA patients with and without tocilizumab treatment were significantly higher when compared to healthy children (p < 0.05). Interestingly, in patients with tocilizumab treatment, serum sIL-6R levels were extremely higher [median (IQR) = 1,110.3 (840.2) ng/mL] than patients without tocilizumab treatment [median (IQR) = 94.2 (82.7) ng/mL]. Conclusion The correlation between serum IL-6 levels and disease activity in patients without tocilizumab treatment was stronger than patients with tocilizumab treatment. In addition, serum sIL-6R levels in patients with tocilizumab treatment were extremely higher than patients without tocilizumab treatment.
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Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed.Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week.Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).
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