Omalizumab In Chronic Spontaneous Urticaria Research Articles

Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria.

The monoclonal anti-immunoglobulin E (IgE) antibody, omalizumab, was the first drug approved for use in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who remain symptomatic despite H1 -antihistamine treatment. Omalizumab binds to free IgE, which lowers free IgE levels and causes FcεRI receptors on basophils and mast cells to be downregulated. It has been shown to improve symptoms of CIU/CSU, but its mechanism of action is not currently understood. Potential mechanisms in CIU/CSU include reducing mast cell releasability, reversing basopenia and improving basophil IgE receptor function, reducing activity of IgG autoantibodies against FcεRI and IgE, reducing activity of IgE autoantibodies against an antigen or autoantigen that has yet to be definitively identified, reducing the activity of intrinsically 'abnormal' IgE, and decreasing in vitro coagulation abnormalities associated with disease activity. However, none of these theories alone or in combination fully account for the pattern of symptom improvement seen with omalizumab therapy, and therefore, no one mechanism is likely to be the definitive mechanism of action. Additional research is needed to further clarify the involvement of omalizumab in relieving symptoms associated with the complex, multifactorial pathogenesis of CIU/CSU.

Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamines: an expert opinion.

Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or intermittent appearance of pruritic wheals (hives), angioedema, or both for six weeks or more, with no known specific trigger. The international EAACI/GA2LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation H1-antihistamines as first-line therapy. However, H1-antihistamine treatment leads to absence of symptoms in fewer than 50% of patients. Updosing of second-generation H1-antihistamines (up to fourfold) as recommended by the EAACI/GA2LEN/EDF/WAO urticaria guideline as second-line therapy, can improve response, but many patients remain symptomatic. Definitions of response are often subjective and a consensus is needed regarding appropriate treatment targets. There is also an unmet need for biomarkers to assess CSU severity and activity and to predict treatment response. The EAACI/GA2LEN/EDF/WAO urticaria guideline recommends add-on omalizumab, ciclosporin A (CsA), or montelukast third-line treatment in patients with an inadequate response to high-dose H1-antihistamines. Omalizumab is currently the only licensed systemic biologic for use in CSU. Both omalizumab and CsA are effective third-line CSU treatments; montelukast appears to have lower efficacy in this setting. Omalizumab carries a label warning for anaphylaxis, although no cases of anaphylaxis were reported in the phase III trials of omalizumab in CSU and it is generally well tolerated in patients with CSU. Omalizumab arguably has a better safety profile than CsA.

Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin

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 (FcεRI+) 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 FcεRI+ 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 FcεRI+ 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 FcεRI 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.

Omalizumab in patients with severe and refractory solar urticaria: A phase II multicentric study

Omalizumab in patients with severe and refractory solar urticaria: A phase II multicentric study

Mechanism of action of the therapy with omalizumab in chronic spontaneous urticaria: is there a role for autoimmunity?

Mechanism of action of the therapy with omalizumab in chronic spontaneous urticaria: is there a role for autoimmunity?

Cost-Utility of Omalizumab Compared With Standard of Care for The Treatment of Chronic Spontaneous Urticaria (Csu)

Chronic spontaneous urticaria (CSU) is characterised by rapid appearance of wheals, angioedema or both, with no obvious cause and with symptoms lasting for more than six weeks; CSU has a demonstrable negative impact on patient quality of life and societal productivity. The objective of this study was to assess the cost-utility of omalizumab compared with continued standard of care (SOC) for the treatment of patients with moderate or severe CSU with an inadequate response to SOC, from the UK societal perspective. A Markov model was developed, defined by five disease severity health states and three additional states for relapse, spontaneous remission and death. The model considered 6 month courses of omalizumab treatment, with re-treatment upon relapse (relapse definition: UAS7≥16) and early discontinuation of non-responders (definition of response: UAS7≤6). Clinical and cost inputs were derived from omalizumab trials and published sources; productivity inputs were informed by a non-interventional study and average earnings data. The base case considered a 20-year time horizon, and cost-utility was expressed as an incremental cost-effectiveness ratio (ICER). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7<16). In the base case analysis, the deterministic ICER was £3,183, with omalizumab being associated with increased costs and increased benefit relative to SOC. Probabilistic sensitivity analysis supported this result. Individual scenarios without early discontinuation of non-responders and adjusting the definition of response had little impact on Results(ICERs £4,409 and £5,304, respectively). Further sensitivity analyses demonstrated robustness of Resultsto changes in key model parameters and inputs. To our knowledge, this is the first economic evaluation of omalizumab in CSU from a UK societal perspective. Omalizumab was associated with consistently low ICERs across a range of different scenarios, demonstrating omalizumab to represent a treatment option with societal benefit for CSU in the UK.

Cost-Effectiveness Of Omalizumab In Chronic Spontaneous Urticaria In The Netherlands

Cost-Effectiveness Of Omalizumab In Chronic Spontaneous Urticaria In The Netherlands

Omalizumab for chronic spontaneous urticaria: a boon for sufferers, but there are unanswered questions.

Omalizumab for chronic spontaneous urticaria: a boon for sufferers, but there are unanswered questions.

Omalizumab in chronic spontaneous urticaria: patient-tailored tapering or planned discontinuation?

Omalizumab in chronic spontaneous urticaria: patient-tailored tapering or planned discontinuation?

Omalizumab in chronic spontaneous urticaria (CSU): experience in three cases

Background Chronic spontaneous urticaria (CSU) is more common in adults, especially middle-aged women. The condition resolves spontaneously within 6 months in 30 to 55% of patients but can persist for years in others. It has a devastating effect on the quality of life of those who experience it. Although the mechanisms are not fully elucidated, anti IgE recombinant humanized monoclonal (Omalizumab) has been recommended, according to the latest guidelines EAACI/GA2LEN/EDF & WAO, with encouraging results in management of refractory CSU as opposed to the usual and alternative therapies.