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Marcus Maurer - One of the best experts on this subject based on the ideXlab platform.
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real life treatment of cholinergic urticaria with Omalizumab
The Journal of Allergy and Clinical Immunology, 2019Co-Authors: Sabine Altrichter, Aida Asady, Mati Chuamanochan, Henriette Knoth, Tatevik Ohanyan, Martin Metz, Marcus MaurerAbstract:Abstract Background Cholinergic urticaria (CholU), a frequent type of chronic inducible urticaria, presents with small itchy wheals upon physical exercise or passive warming. Omalizumab has been shown to be very effective in patients with chronic spontaneous urticaria. Whether or not Omalizumab is also effective in CholU is largely unknown. Aim To assess the effectiveness of Omalizumab treatment in CholU Method We assessed the effects of real life Omalizumab treatment at standard and higher than standard doses in CholU patients including their time to response, the effects on concomitant urticaria forms and links to clinical features. Results Of 16 CholU patients treated with Omalizumab, 11 (68%) reported a major or complete response, 2 patients reported a minor effect (13 %) and 3 patients (19%) showed no benefit. Omalizumab updosing led to complete response in 4 of 6 patients, who did not achieve controlled disease on standard dosed Omalizumab therapy, i.e. 300 mg/4wks. Time to onset of benefit was fast, and concomitant urticaria forms showed similar response patterns. Treatment effects were linked to patient gender, with better responses in female patients (p Conclusion Omalizumab treatment is effective in the majority of CholU patients, especially in female patients. Most non-responders to standard-dosed Omalizumab benefit from updosing. Our findings call for controlled clinical trials of Omalizumab and other IgE-targeted treatments in CholU.
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the clinical response to Omalizumab in chronic spontaneous urticaria patients is linked to and predicted by ige levels and their change
Allergy, 2018Co-Authors: Ragip Ertas, Kemal Ozyurt, Mustafa Atasoy, Tomasz Hawro, Marcus MaurerAbstract:BACKGROUND Omalizumab is an effective and well-tolerated treatment for chronic spontaneous urticaria (CSU). Markers and predictors of response are largely unknown, but needed to optimize Omalizumab treatment. Omalizumab targets IgE, and IgE levels may be linked to the effects of treatment. We evaluated whether response rates to treatment with Omalizumab in patients with CSU are linked to their baseline IgE levels, their IgE levels after Omalizumab treatment, and the ratio of on treatment IgE and baseline IgE levels. METHODS Chronic spontaneous urticaria (CSU) patients (n = 113) were treated with Omalizumab 300 mg/4 weeks for 12 weeks, when their treatment responses, that is, no, partial, or complete response, were assessed by use of the urticaria activity score, physician and patient visual analog scale, and treatment effectiveness score. Total IgE levels were measured before treatment (bIgE) with Omalizumab and 4 weeks thereafter (w4IgE). RESULTS Nonresponders to Omalizumab had significantly lower bIgE levels (17.9, 17.0-55.0 IU/mL) than partial responders (82.0, 46.2-126.5 IU/mL, P = .008) and complete responders (73.7, 19.45-153.8 IU/mL, P = .032). Nonresponders also had lower w4IgE levels and lower ratios of w4IgE/bIgE levels than partial and complete responders (P < .001). Nonresponse to Omalizumab was best predicted by patients' w4IgE/bIgE ratios, significantly better than by bIgE levels (P = .016). CONCLUSIONS In CSU, total IgE levels and their change predict the response to treatment with Omalizumab. The assessment of pre- and post-treatment IgE levels and their ratio may help to improve the management of CSU in patients who require Omalizumab treatment.
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effect of Omalizumab on angioedema in h1 antihistamine resistant chronic spontaneous urticaria patients results from x act a randomized controlled trial
Allergy, 2016Co-Authors: Petra Staubach, Martin Metz, Nadine Chapmanrothe, Christian Sieder, Matthias Brautigam, Janice Canvin, Marcus MaurerAbstract:Background Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. Objective The primary objective was to evaluate the efficacy of Omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. Methods X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to Omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Results Of the 91 patients randomized to Omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (Omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P < 0.001). There was a threefold improvement in angioedema-burdened days/week with Omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57–63 days with Omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema-specific QoL (P < 0.001). The adverse events reported are in line with the established safety profile of Omalizumab. Conclusion Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment.
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Omalizumab for the treatment of chronic spontaneous urticaria a meta analysis of randomized clinical trials
The Journal of Allergy and Clinical Immunology, 2016Co-Authors: Marcus Maurer, Tomasz Hawro, Zuotao Zhao, Ling Meng, Jifu WeiAbstract:Background Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a promising new treatment option. As of now, however, the efficacy and safety of different doses of Omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized. Objective We sought to assess the efficacy and safety of different doses of Omalizumab for the treatment of CSU in a meta-analysis of clinical trial results. Methods Suitable trials were identified by searching PubMed, Medline, Embase, and Web of Science databases and with the help of Omalizumab's manufacturers. Only double-blind, randomized, placebo-controlled studies with Omalizumab-treated versus placebo-treated patients with CSU were included in this analysis. Results We identified 7 randomized, placebo-controlled studies with 1312 patients with CSU. Patients treated with Omalizumab (75-600 mg every 4 weeks) had significantly reduced weekly itch and weekly wheal scores compared with the placebo group. Omalizumab's effects were dose dependent, with the strongest reduction in weekly itch and weekly wheal scores observed with 300 mg. Rates of complete response were significantly higher in the Omalizumab group (relative risk, 4.55; P Conclusion This meta-analysis provides high-quality evidence for the efficacy and safety of Omalizumab in patients with CSU and for treating these patients with 300 mg of Omalizumab every 4 weeks.
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similar efficacy with Omalizumab in chronic idiopathic spontaneous urticaria despite different background therapy
The Journal of Allergy and Clinical Immunology: In Practice, 2015Co-Authors: Thomas B. Casale, Marcus Maurer, Allen P. Kaplan, Jonathan A. Bernstein, Benjamin Trzaskoma, Sarbjit S Saini, Hubert Chen, C E H Grattan, Ana Gimenezarnau, Karin RosénAbstract:Background Data from the 3 Omalizumab pivotal trials in patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) represent the largest database of patients reported to date with refractory disease (Omalizumab, n = 733; placebo, n = 242). Objective The objective of this study was to compare results from ASTERIA I and II, which included only approved doses of H 1 -antihistamine as background therapy based on regulatory authority requirements, to those from GLACIAL, which permitted higher doses of H 1 -antihistamines as well as other types of background therapy, in a post hoc analysis. Methods Efficacy data from the placebo, Omalizumab 150-mg, and Omalizumab 300-mg treatment arms of ASTERIA I and II were pooled and analyzed (n = 162 and n = 160, respectively). The 300-mg treatment arm analyses were compared with the analysis of data from GLACIAL (n = 252) using analysis of covariance models. The key efficacy endpoint was change from baseline to week 12 in mean weekly itch severity score (ISS); other endpoints were also evaluated. Safety data were pooled from all 3 studies. Results Mean ISS was significantly reduced from baseline at week 12 in the pooled ASTERIA I and II Omalizumab 150- and 300-mg treatment arms and in the GLACIAL Omalizumab 300-mg arm. The weekly ISS reduction magnitude at week 12 was similar between the Omalizumab 300-mg groups in the ASTERIA I and II pooled and GLACIAL studies. Similar treatment effect sizes were observed across multiple endpoints. Omalizumab was well tolerated and the adverse-event profile was similar regardless of background therapy for CIU/CSU. The overall safety profile was generally consistent with Omalizumab therapy in allergic asthma. Conclusion Omalizumab 300 mg was safe and effective in reducing CIU/CSU symptoms regardless of background therapy.
Martin Metz - One of the best experts on this subject based on the ideXlab platform.
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real life treatment of cholinergic urticaria with Omalizumab
The Journal of Allergy and Clinical Immunology, 2019Co-Authors: Sabine Altrichter, Aida Asady, Mati Chuamanochan, Henriette Knoth, Tatevik Ohanyan, Martin Metz, Marcus MaurerAbstract:Abstract Background Cholinergic urticaria (CholU), a frequent type of chronic inducible urticaria, presents with small itchy wheals upon physical exercise or passive warming. Omalizumab has been shown to be very effective in patients with chronic spontaneous urticaria. Whether or not Omalizumab is also effective in CholU is largely unknown. Aim To assess the effectiveness of Omalizumab treatment in CholU Method We assessed the effects of real life Omalizumab treatment at standard and higher than standard doses in CholU patients including their time to response, the effects on concomitant urticaria forms and links to clinical features. Results Of 16 CholU patients treated with Omalizumab, 11 (68%) reported a major or complete response, 2 patients reported a minor effect (13 %) and 3 patients (19%) showed no benefit. Omalizumab updosing led to complete response in 4 of 6 patients, who did not achieve controlled disease on standard dosed Omalizumab therapy, i.e. 300 mg/4wks. Time to onset of benefit was fast, and concomitant urticaria forms showed similar response patterns. Treatment effects were linked to patient gender, with better responses in female patients (p Conclusion Omalizumab treatment is effective in the majority of CholU patients, especially in female patients. Most non-responders to standard-dosed Omalizumab benefit from updosing. Our findings call for controlled clinical trials of Omalizumab and other IgE-targeted treatments in CholU.
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clinical efficacy of Omalizumab in chronic spontaneous urticaria is associated with a reduction of fceri positive cells in the skin
Theranostics, 2017Co-Authors: Martin Metz, Petra Staubach, Andrea Bauer, Randolf Brehler, Janine Gericke, Michael Kangas, Joanna Ashtonchess, Philip Jarvis, Panayiotis Georgiou, Janice CanvinAbstract:Background. Treatment with Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of Omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of Omalizumab on levels of high affinity IgE receptor-positive (FceRI+) and IgE-positive (IgE+) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg Omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks. Changes in disease activity were assessed by use of the weekly Urticaria Activity Score (UAS7). Circulating IgE levels, basophil numbers and levels of expression of FceRI+ and IgE+ cells in the skin and in blood basophils were determined. Results. Patients receiving Omalizumab showed a significantly greater decrease in UAS7 compared with patients receiving placebo. At Week 12 the mean difference in UAS7 between treatment groups was -14.82 (p=0.0027), consistent with previous studies. Total IgE levels in serum were increased after Omalizumab treatment and remained elevated up to Week 12. Free IgE levels decreased after Omalizumab treatment. Mean levels of FceRI+ skin cells in patients treated with Omalizumab 300 mg were decreased at Week 12 compared with baseline in the dermis of both non-lesional and lesional skin, reaching levels comparable with those seen in healthy volunteers (HVs). There were no statistically significant changes in mean FcɛRI+ cell levels in the placebo group. Similar results were seen for changes in IgE+ cells, although the changes were not statistically significant. The level of peripheral blood basophils increased immediately after treatment start and returned to Baseline values after the follow-up period. The levels of FceRI and IgE expression on peripheral blood basophils were rapidly reduced by Omalizumab treatment up to Week 12. Conclusions. Treatment with Omalizumab resulted in rapid clinical benefits in patients with CSU. Treatment with Omalizumab was associated with reduction in FcɛRI+ and IgE+ basophils and intradermal cells.
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effect of Omalizumab on angioedema in h1 antihistamine resistant chronic spontaneous urticaria patients results from x act a randomized controlled trial
Allergy, 2016Co-Authors: Petra Staubach, Martin Metz, Nadine Chapmanrothe, Christian Sieder, Matthias Brautigam, Janice Canvin, Marcus MaurerAbstract:Background Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. Objective The primary objective was to evaluate the efficacy of Omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. Methods X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to Omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Results Of the 91 patients randomized to Omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (Omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P < 0.001). There was a threefold improvement in angioedema-burdened days/week with Omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57–63 days with Omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema-specific QoL (P < 0.001). The adverse events reported are in line with the established safety profile of Omalizumab. Conclusion Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment.
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retreatment with Omalizumab results in rapid remission in chronic spontaneous and inducible urticaria
JAMA Dermatology, 2014Co-Authors: Martin Metz, Tatevik Ohanyan, Martin K Church, Marcus MaurerAbstract:Importance Omalizumab has emerged as a novel and effective treatment option for patients with antihistamine-resistant chronic urticaria. It is unclear whether patients with recurrent urticaria symptoms after discontinuation of Omalizumab treatment can benefit from retreatment. Objective To assess the response of patients with chronic urticaria who receive Omalizumab retreatment. Design, Setting, and Participants Retrospective analyses were conducted of outpatients treated at an urticaria specialist center of a university hospital. Participants included 25 consecutive patients (aged 18-74 years; 18 women) with chronic spontaneous urticaria, chronic inducible urticaria, or both who showed complete response to Omalizumab treatment, experienced relapse after discontinuation of treatment, and received retreatment with Omalizumab. Interventions Subcutaneous treatment with Omalizumab (150-600 mg/mo). Main Outcomes and Measures Response after retreatment was assessed by the urticaria activity score in patients with chronic spontaneous urticaria and by trigger threshold testing (in patients with cold urticaria or symptomatic dermographism) and/or a carefully determined history (in patients with cholinergic urticaria, solar urticaria, or pressure urticaria). Adverse events were documented. Results All patients experienced complete response after retreatment. None of the patients reported relevant adverse events during Omalizumab treatment and retreatment. Conclusions and Relevance Omalizumab retreatment is effective and safe in patients with chronic urticaria who have benefited from initial Omalizumab treatment.
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Omalizumab is an effective and rapidly acting therapy in difficult to treat chronic urticaria a retrospective clinical analysis
Journal of Dermatological Science, 2014Co-Authors: Martin Metz, Tatevik Ohanyan, Martin K Church, Marcus MaurerAbstract:Abstract Background Omalizumab (anti-IgE) therapy is effective and safe in chronic urticaria (CU) in placebo-controlled clinical trials but real life clinical data are scarce. Objective To better understand the effects of Omalizumab in CU patients treated outside of clinical trials. Methods In this retrospective clinical analysis, we assessed responder rates, optimal dosage, response to up-/downdosing, time to relief of symptoms, rates of return and time of relapse after Omalizumab administration, and safety in 51 CU patients, 20 with chronic spontaneous urticaria (CSU) alone, 21 with different forms of chronic inducible urticaria (CindU) and 10 with both. Results Omalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients. When starting with 150 mg Omalizumab 4 weekly, only 2/15 CSU and 7/17 CindU patients required updosing to achieve complete remission. In CSU, 57% of complete responses occurred within week one, all on the first day. Relapses were 2–8 weeks in all but six patients, where they were Conclusion Clinical experience from more than 1250 injections in 51 patients over four years indicates that Omalizumab is a rapidly acting, highly effective and safe drug in CSU and CindU patients. Our observations in a real life clinical setting support the recommendation of current EAACI/GA 2 LEN/EDF/WAO guideline for the management of urticaria to use Omalizumab to treat urticaria patients.
Janice Canvin - One of the best experts on this subject based on the ideXlab platform.
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clinical efficacy of Omalizumab in chronic spontaneous urticaria is associated with a reduction of fceri positive cells in the skin
Theranostics, 2017Co-Authors: Martin Metz, Petra Staubach, Andrea Bauer, Randolf Brehler, Janine Gericke, Michael Kangas, Joanna Ashtonchess, Philip Jarvis, Panayiotis Georgiou, Janice CanvinAbstract:Background. Treatment with Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of Omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of Omalizumab on levels of high affinity IgE receptor-positive (FceRI+) and IgE-positive (IgE+) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg Omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks. Changes in disease activity were assessed by use of the weekly Urticaria Activity Score (UAS7). Circulating IgE levels, basophil numbers and levels of expression of FceRI+ and IgE+ cells in the skin and in blood basophils were determined. Results. Patients receiving Omalizumab showed a significantly greater decrease in UAS7 compared with patients receiving placebo. At Week 12 the mean difference in UAS7 between treatment groups was -14.82 (p=0.0027), consistent with previous studies. Total IgE levels in serum were increased after Omalizumab treatment and remained elevated up to Week 12. Free IgE levels decreased after Omalizumab treatment. Mean levels of FceRI+ skin cells in patients treated with Omalizumab 300 mg were decreased at Week 12 compared with baseline in the dermis of both non-lesional and lesional skin, reaching levels comparable with those seen in healthy volunteers (HVs). There were no statistically significant changes in mean FcɛRI+ cell levels in the placebo group. Similar results were seen for changes in IgE+ cells, although the changes were not statistically significant. The level of peripheral blood basophils increased immediately after treatment start and returned to Baseline values after the follow-up period. The levels of FceRI and IgE expression on peripheral blood basophils were rapidly reduced by Omalizumab treatment up to Week 12. Conclusions. Treatment with Omalizumab resulted in rapid clinical benefits in patients with CSU. Treatment with Omalizumab was associated with reduction in FcɛRI+ and IgE+ basophils and intradermal cells.
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effect of Omalizumab on angioedema in h1 antihistamine resistant chronic spontaneous urticaria patients results from x act a randomized controlled trial
Allergy, 2016Co-Authors: Petra Staubach, Martin Metz, Nadine Chapmanrothe, Christian Sieder, Matthias Brautigam, Janice Canvin, Marcus MaurerAbstract:Background Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. Objective The primary objective was to evaluate the efficacy of Omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. Methods X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to Omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Results Of the 91 patients randomized to Omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (Omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P < 0.001). There was a threefold improvement in angioedema-burdened days/week with Omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57–63 days with Omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema-specific QoL (P < 0.001). The adverse events reported are in line with the established safety profile of Omalizumab. Conclusion Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment.
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Omalizumab and the risk of malignancy results from a pooled analysis
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: William W Busse, R. Buhl, Mark D. Eisner, M Blogg, Carlos Fernandez Vidaurre, Jin Zhu, Janice CanvinAbstract:Background Since initial registration, the Omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of Omalizumab showed a numeric imbalance in malignancies arising in Omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. Objective We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of Omalizumab-treated patients. Methods This pooled analysis included data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, double-blind, placebo-controlled (RDBPC) trials. Results There were 11,459 unique patients in all clinical trials (7,789 received Omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 Omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for Omalizumab- and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. Conclusions In this pooled analysis no association was observed between Omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between Omalizumab therapy and malignancy is unlikely.
Thomas B. Casale - One of the best experts on this subject based on the ideXlab platform.
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Omalizumab effectiveness by biomarker status in patients with asthma evidence from prospero a prospective real world study
The Journal of Allergy and Clinical Immunology: In Practice, 2019Co-Authors: Thomas B. Casale, Benjamin Trzaskoma, William W Busse, Allan T Luskin, Robert S Zeiger, Ming Yang, Noelle M Griffin, Bradley E ChippsAbstract:Background Omalizumab has demonstrated efficacy in clinical trials of patients with asthma, but real-world data are needed. Objective To assess outcomes after Omalizumab initiation in patients with asthma in a real-world setting. Methods Patients aged 12 years and older with allergic asthma who were candidates for Omalizumab on the basis of physician-assessed need were enrolled in a US-based, prospective, single-arm, 48-week multicenter study, the Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab. Monthly assessments included exacerbations, health care utilization, asthma control test (ACT), and adverse events. At baseline, 6 months, and end of study, biomarkers (blood eosinophils and fractional exhaled nitric oxide) were collected and spirometry performed. Results Of 806 enrollees, 801 (99.4%) received Omalizumab and 622 (77.2%) completed the study. The exacerbation rate significantly improved from a mean of 3.00 ± 3.28 in the 12 months before baseline to 0.78 ± 1.37 through month 12 (P Conclusions Omalizumab initiation in patients with asthma resulted in improved exacerbation rates, reduced hospitalizations, and improved ACT scores compared with pretreatment values, regardless of biomarker status.
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similar efficacy with Omalizumab in chronic idiopathic spontaneous urticaria despite different background therapy
The Journal of Allergy and Clinical Immunology: In Practice, 2015Co-Authors: Thomas B. Casale, Marcus Maurer, Allen P. Kaplan, Jonathan A. Bernstein, Benjamin Trzaskoma, Sarbjit S Saini, Hubert Chen, C E H Grattan, Ana Gimenezarnau, Karin RosénAbstract:Background Data from the 3 Omalizumab pivotal trials in patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) represent the largest database of patients reported to date with refractory disease (Omalizumab, n = 733; placebo, n = 242). Objective The objective of this study was to compare results from ASTERIA I and II, which included only approved doses of H 1 -antihistamine as background therapy based on regulatory authority requirements, to those from GLACIAL, which permitted higher doses of H 1 -antihistamines as well as other types of background therapy, in a post hoc analysis. Methods Efficacy data from the placebo, Omalizumab 150-mg, and Omalizumab 300-mg treatment arms of ASTERIA I and II were pooled and analyzed (n = 162 and n = 160, respectively). The 300-mg treatment arm analyses were compared with the analysis of data from GLACIAL (n = 252) using analysis of covariance models. The key efficacy endpoint was change from baseline to week 12 in mean weekly itch severity score (ISS); other endpoints were also evaluated. Safety data were pooled from all 3 studies. Results Mean ISS was significantly reduced from baseline at week 12 in the pooled ASTERIA I and II Omalizumab 150- and 300-mg treatment arms and in the GLACIAL Omalizumab 300-mg arm. The weekly ISS reduction magnitude at week 12 was similar between the Omalizumab 300-mg groups in the ASTERIA I and II pooled and GLACIAL studies. Similar treatment effect sizes were observed across multiple endpoints. Omalizumab was well tolerated and the adverse-event profile was similar regardless of background therapy for CIU/CSU. The overall safety profile was generally consistent with Omalizumab therapy in allergic asthma. Conclusion Omalizumab 300 mg was safe and effective in reducing CIU/CSU symptoms regardless of background therapy.
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Safety and tolerability of Omalizumab
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2009Co-Authors: J. Corren, Thomas B. Casale, B.q. Lanier, R. Buhl, S. T. Holgate, Pablo JimenezAbstract:Summary Background Omalizumab (Xolair®) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. Objective To review clinical study data to assess the safety profile of Omalizumab. Methods We analysed the safety of Omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia. Results Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in Omalizumab-treated patients and 0.07% in control patients. No Omalizumab-treated patient developed measurable anti-Omalizumab antibodies. Post-marketing, based on estimated exposure of 57 300 patients (June 2003–December 2006), the frequency of anaphylaxis attributed to Omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with Omalizumab. Conclusion Data indicate that the proven efficacy of add-on Omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.
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Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed induced seasonal allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Thomas B. Casale, William W Busse, Joel N Kline, Zuhair K Ballas, Mark H Moss, Robert G Townley, Masoud Mokhtarani, Vicki Seyfertmargolis, Adam Asare, Kirk BatemanAbstract:Background Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis. Objectives We hypothesized that Omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT. Methods Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of Omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 μg Amb a 1) or placebo immunotherapy, then 12 weeks of Omalizumab or placebo plus immunotherapy. Results Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in Omalizumab patients. Patients receiving Omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of Omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both Omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044). Conclusion Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with Omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.
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the anti inflammatory effects of Omalizumab confirm the central role of ige in allergic inflammation
The Journal of Allergy and Clinical Immunology, 2005Co-Authors: Stephen T. Holgate, Thomas B. Casale, Jean Bousquet, Sally E Wenzel, Yamo Deniz, C ReisnerAbstract:Anti-IgE therapy with Omalizumab reduces serum levels of free IgE and downregulates expression of IgE receptors (FceRI) on mast cells and basophils. In the airways of patients with mild allergic asthma, Omalizumab reduces FceRI + and IgE + cells and causes a profound reduction in tissue eosinophilia, together with reductions in submucosal T-cell and B-cell numbers. In patients with seasonal allergic rhinitis, Omalizumab inhibits the allergen-induced seasonal increases in circulating and tissue eosinophils. Omalizumab decreases FceRI expression on circulating dendritic cells, which might lead to a reduction in allergen presentation, T H 2 cell activation, and proliferation. As a systemic anti-IgE agent, Omalizumab has demonstrated clinical efficacy in patients with moderate and severe allergic asthma and in those with seasonal and perennial allergic rhinitis, as well as in patients with concomitant allergic asthma and allergic rhinitis. The anti-inflammatory effects of Omalizumab at different sites of allergic inflammation and the clinical benefits of anti-IgE therapy in patients with allergic asthma and allergic rhinitis emphasize the fundamental importance of IgE in allergic inflammation.
M Blogg - One of the best experts on this subject based on the ideXlab platform.
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Omalizumab and the risk of malignancy results from a pooled analysis
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: William W Busse, R. Buhl, Mark D. Eisner, M Blogg, Carlos Fernandez Vidaurre, Jin Zhu, Janice CanvinAbstract:Background Since initial registration, the Omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of Omalizumab showed a numeric imbalance in malignancies arising in Omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. Objective We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of Omalizumab-treated patients. Methods This pooled analysis included data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, double-blind, placebo-controlled (RDBPC) trials. Results There were 11,459 unique patients in all clinical trials (7,789 received Omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 Omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for Omalizumab- and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. Conclusions In this pooled analysis no association was observed between Omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between Omalizumab therapy and malignancy is unlikely.
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asthma symptom re emergence after Omalizumab withdrawal correlates well with increasing ige and decreasing pharmacokinetic concentrations
The Journal of Allergy and Clinical Immunology, 2009Co-Authors: Raymond G Slavin, Caterina Ferioli, Stacey Tannenbaum, C Martin, M Blogg, Philip J LoweAbstract:Background Physicians have questioned whether Omalizumab can be discontinued or the dose reduced after clinical improvement is seen in patients with severe asthma. Objectives To examine the relationships among Omalizumab, free IgE, and clinical outcomes in a randomized, placebo-controlled trial in patients with severe persistent allergic asthma following a posology based on pretreatment total IgE and body weight. Methods A pharmacokinetic-pharmacodynamic binding model was used to calculate free IgE, Omalizumab, and total IgE concentrations during the 28-week treatment and 16-week follow-up of the INvestigation of Omalizumab in seVere Asthma TrEatment (INNOVATE) study. These were plotted against the mean changes in the total asthma symptom score, morning peak expiratory flow, and rescue medication use for physician-defined treatment responders and nonresponders. Results The model accurately fitted Omalizumab and free and total IgE, allowing reconstruction of the entire time course for each patient. Free IgE was rapidly suppressed below the 50 ng/mL (20.8 IU/mL) target, although there was a notable period before clinical measures stabilized. After treatment cessation, free IgE and Omalizumab returned toward baseline and, after a delay, asthma symptoms re-emerged. Model-derived Omalizumab and free IgE concentrations correlated well with changes in clinical outcomes, particularly in Omalizumab-treated responders. Asthma symptoms exhibited different correlations during response onset compared with response offset (hysteresis), indicative of physiological time delays between changes in IgE levels and pulmonary function. Conclusion Omalizumab and free IgE correlated well with clinical symptoms. Reducing Omalizumab doses below those in the dosing table cannot be recommended; the resulting increase in free IgE would cause a deterioration in asthma control.
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predicting and evaluating response to Omalizumab in patients with severe allergic asthma
Respiratory Medicine, 2007Co-Authors: J Bousquet, Marc Humbert, K F Rabe, H Fox, Kian Fan Chung, W Berger, G Ayre, Haixiao Chen, K Thomas, M BloggAbstract:Summary Background Omalizumab is a monoclonal antibody indicated for treatment of severe persistent allergic asthma inadequately controlled despite optimal controller therapy. We investigated whether patient selection could be targeted further. Methods Data from seven randomized controlled Omalizumab trials were analyzed to investigate whether pre-treatment patient baseline clinical characteristics could be identified that were predictive of a superior response to Omalizumab. We also studied whether patients who respond to Omalizumab following a course of treatment could be reliably identified. Univariate/multivariate analyses of INNOVATE data were performed to identify predictive baseline measures and further investigated in efficacy analyses of pooled data from seven studies. The best method of identifying responders to Omalizumab following treatment was determined by assessing the ability of various clinical response criteria to identify responders and discriminate patient exacerbation and other outcomes. Results Baseline total immunoglobulin E (IgE) was the only predictor of efficacy in INNOVATE. However, pooled analysis showed treatment benefits irrespective of IgE levels. In Omalizumab-treated patients, physician's overall assessment following a course of treatment identified 61% as responders and best discriminated treatment outcomes. Conclusion Baseline characteristics do not reliably predict benefit with Omalizumab. Physician's overall assessment after 16 weeks of treatment is the most meaningful measure of response to therapy.
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efficacy and tolerability of anti immunoglobulin e therapy with Omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis solar
Allergy, 2004Co-Authors: Antonio M Vignola, Marc Humbert, M Blogg, Jean Bousquet, Louis Philippe Boulet, S Hedgecock, H Fox, K SurreyAbstract:Background: Anti-IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety of Omalizumab in patients with concomitant moderate-to-severe asthma and persistent allergic rhinitis. Methods: This multicentre, randomized, double-blind, parallel-group, placebocontrolled trial evaluated the safety and efficacy of Omalizumab. A total of 405 patients (12–74 years) with a stable treatment (‡ 400 lg budesonide Turbuhaler � )a nd‡ 2 unscheduled medical visits for asthma during the past year or ‡ 3 during the past 2 years were enrolled. Patients received Omalizumab (‡ 0.016 mg/kg/IgE [IU/ml] per 4 weeks) or placebo for 28 weeks. Results: Fewer patients treated with Omalizumab experienced asthma exacerbations (20.6%) than placebo-treated patients (30.1%), P ¼ 0.02. A clinically significant (‡ 1.0 point) improvement in both Asthma Quality of Life Questionnaire and Rhinitis Quality of Life Questionnaire occurred in 57.7% of Omalizumab patients compared with 40.6% of placebo patients (P < 0.001). Omalizumab reduced Wasserfallen symptom scores for asthma (P ¼ 0.023), rhinitis (P < 0.001) and the composite asthma/rhinitis scores (P < 0.001) compared with placebo. Serious adverse events were observed in 1.4% of Omalizumab-treated patients and 1.5% of placebo-treated patients. Conclusion: Omalizumab is well tolerated and effective in preventing asthma exacerbations and improving quality of life in patients with concomitant asthma and persistent allergic rhinitis.
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efficacy and tolerability of anti immunoglobulin e therapy with Omalizumab in patients with poorly controlled moderate to severe allergic asthma
Allergy, 2004Co-Authors: Jon G Ayres, M Blogg, G Ayre, B Higgins, Edwin R Chilvers, H FoxAbstract:Background: Patients with poorly controlled asthma have greater morbidity and mortality. This study evaluated the efficacy and tolerability of Omalizumab in patients with poorly controlled, moderate-to-severe allergic asthma. Methods: This was a randomized, open-label, multicentre, parallel-group study. A total of 312 patients (12–73 years) receiving ≥400 μg/day (adolescent) or ≥800 μg/day (adult) inhaled beclomethasone dipropionate, or equivalent were included. Patients received best standard care (BSC) with or without Omalizumab [at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks] for 12 months. Results: The annualized mean number of asthma deterioration-related incidents was reduced from 9.76 with BSC alone (n = 106) to 4.92 per patient-year with Omalizumab (n = 206) (P < 0.001). Mean clinically significant asthma exacerbation rates were 2.86 and 1.12 per patient-year, respectively (P < 0.001). Omalizumab-treated patients (41.4%) required rescue medication <1 day/week compared with 20.7% for BSC alone (P < 0.001). Omalizumab improved absolute forced expiratory volume in 1 s (FEV1) compared with BSC alone (2.48 and 2.28l, respectively; P < 0.05) and reduced symptom scores relative to BSC alone (decrease of 6.5 and 0.7 respectively; P < 0.001). Omalizumab was well-tolerated. Conclusions: Omalizumab administered as add-on therapy to BSC benefits patients with poorly controlled, moderate-to-severe allergic asthma.
