Refractory Chronic Spontaneous Urticaria Research Articles

Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study.

For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

Evaluating the efficacy and safety of biologic and oral drugs for refractory chronic spontaneous urticaria: Systematic review and network meta-analysis

Evaluating the efficacy and safety of biologic and oral drugs for refractory chronic spontaneous urticaria: Systematic review and network meta-analysis

Treatment options in refractory chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) patients sometimes do not respond to second-generation antihistamine, and 10-50% patients do not even respond to four-fold the usual dose of nonsedating H1 antihistamine, which further leads to repeated courses of oral corticosteroids to abate the symptoms. There are third-line agents approved by EAACI guidelines, which include omalizumab and cyclosporine. Certain patients are even resistant to the third-line agents. In this review, various other treatment options will be discussed in patients of refractory CSU. Recently, we demonstrated azathioprine as a possible third-line option, which was found noninferior to cyclosporine in antihistamine refractory CSU. There have been trials, studies, case series and reports, which suggest other putative options for refractory CSU management. Studies on the management of refractory CSU are accumulating thereby expanding the armamentarium of dermatologists and allergologist against difficult-to-treat urticaria patients.

The socio-economic burden of H1-antihistamine-refractory chronic spontaneous urticaria in Germany.

Data from the AWARE study (A Worldwide Antihistamine-Refractory chronic urticaria patient Evaluation) illustrate a substantial disease burden in German patients with H1-antihistamine (-H1-AH)-refractory chronic spontaneous urticaria (CSU). Detrimental effects on patients' quality of life, poor disease control and impairment in the ability to work and perform other daily activities are reported. Based on these findings, this study aims to quantify the epidemiological and socio-economic burden of H1-AH-refractory CSU in Germany. To determine the epidemiological burden of H1-AH-refractory CSU, the age- and gender-specific prevalence of CSU and the proportion of H1-AH-refractory patients in Germany anonymized data from the InGef research database have been used. In a second step, the socio-economic burden in terms of lost numbers of hours in paid and unpaid work was calculated by extrapolating the age- and gender-specific work productivity and activity impairment (WPAI) observed in AWARE to the H1-AH-refractory CSU population in Germany. Finally, productivity losses in paid and unpaid work were monetized using the human capital and the friction cost approach respectively. Moreover, socio-economic burden was calculated depending on symptom control of the patients (measured by urticaria control test [UCT]). In Germany, over 203,000 patients (20 years or older) had H1-AH-refractory CSU in 2018. The avoided lost paid and unpaid work hours attributable to H1-AH-refractory CSU summed up to over 100 million. Overall, the socio-economic burden of H1-AH-refractory CSU in monetary terms was evaluated at € 2.2 billion and the majority of this was due to unpaid work loss. Patients with poor disease control, as indicated by UCT score < 12, were more likely to suffer from high impairment than patients with controlled disease, resulting in a higher socio-economic burden. The results of our analyses picture the substantial socio-economic burden of H1-AH-refractory CSU and therefore the tremendous impact it has on daily lives of individuals and society overall.

Bilastine in Refractory Chronic Spontaneous Urticaria: Disease Control and Cytokine Modulation in an Open-label Prospective Study.

The treatment options for chronic spontaneous urticaria (CSU) primarily include second generation non-sedative antihistamine (SGAHs). Bilastine is a newer, nonsedating SGAH approved for urticaria in February 2019 by the Drugs Controller General of India. Its major advantages are in terms of superior efficacy, lack of drug interactions and adverse effects, including sedation, compared to conventional SGAHs. The role of cytokines in the pathogenesis of CSU is well known. However, there is a shortage of data regarding the change in serum levels of proinflammatory cytokines following H1 antihistamines. We conducted this trial to evaluate the role of bilastine in cytokine modulation and autoimmunity, thereby explaining its role in modifying the disease process in CSU. This prospective study was conducted in a tertiary institute in Kolkata on patients aged 12 years and above with a CSU >6 months. These patients had an unsatisfactory response, as per the Urticaria Activity Score 7 (UAS7), to previous antihistamine therapies in standard doses. Treatment effectiveness was determined by comparing the UAS7 at baseline with that at weeks 4, 8 and 12. Also, baseline serum interleukin-6 (IL-6) and IL-17 were compared with those at the end of the study, that is, 12 weeks. Thirty patients who matched the inclusion criteria and signed informed consent were included in the study. At the end of 12 weeks, 10% of patients (n = 3) achieved a complete treatment response (UAS = 0), whereas 43.33% of patients (n = 13) were labelled as having well-controlled urticaria (UAS <6). At 12 weeks, the mean UAS7 score (6.47 ± 4.45) was statistically significant compared to the baseline score (25.47 ± 7.74). The mean values of serum IL-6 (pg/ml) and IL-17 (pg/ml) at baseline were 5.96 ± 5.24 pg/ml and 6.96 ± 5.97 pg/ml, respectively. At the end of treatment, that is, 3 months, the mean values were reduced to 4.61 ± 4.56 pg/ml and 5.08 ± 3.87 pg/ml. The reduction was statistically significant for both serum IL-6 (P < 0.001) and IL-17 (P < 0.0001). We conclude that bilastine at a once-daily continuous dose of 40 mg for 3 months is safe and effective in CSU patients who are refractory to treatment at the standard doses of SGAHs. Improved symptomatic control with bilastine was also associated with better control over the inflammatory process, as suggested by the lowering of mean cytokine levels in our study.

Oral tofacitinib in refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a skin condition marked by the emergence of wheals on their own that persist for six weeks or more. CSU is quite common, affecting up to 1% of the population, and has a serious detrimental effect on a patient's health and quality of life. Antihistamines (AH) are currently the backbone of treatment for chronic urticaria (CU), however up to 40% of patients do not respond to even large (four-fold) daily dosages of AH. Tofacitinib is a small-molecule that inhibits intracellular signalling of several important cytokines involved in the inflammatory cascade and blocks JAK1/3. While there are reports of tofacitinib's positive effects in patients with mast cell activation disorder, there are none in those with urticaria. The aim of our study is to assess the efficacy of oral tofacitinib in refractory chronic spontaneous urticaria. 5 cases of refractory CSU between the age group of 20 to 40 years were included in our study and they were followed up for 6 months. The patients were started on oral tofacitinib 5mg twice a day. On every weekly follow-up, we used clinical assessment, urticaria activity score and urticaria control test to evaluate the treatment response The usage of oral tofacitinib significantly improves the clinical picture in refractory CSU. Although more research is required to determine Tofacitinib's effectiveness in CSU, our study raises the possibility that it could represent a novel therapeutic option for individuals with refractory CSU.

The effectiveness of omalizumab therapy in patients with chronic spontaneous urticaria: the experience of a single-centre study in Poland.

Omalizumab, which is a recombinant, humanised anti-immunoglobulin-E antibody, is the only approved drug for antihistamine refractory chronic spontaneous urticaria (CSU). It has been reported that it is an effective and safe drug, but the data about long-term effectiveness are still lacking. To perform a retrospective analysis of the patients with CSU treated with omalizumab at the dermatology department to assess effectiveness of omalizumab therapy in the single centre in Poland. A two-and-a-half-year retrospective analysis of patients with CSU undergoing the therapy with omalizumab was conducted. Patients' data were analysed for many factors such as age, gender, severity indexes (UAS7, DLQI), duration and effects of the treatment used. Sixty-one patients with CSU have been treated with omalizumab in the drug program. The number of female patients - 42 (68.9%) significantly dominated over the number of male patients - 19 (31.1%). The mean UAS7 during the first course of treatment declined from 33.2 to 2.8, during the second from 30.9 to 1.7 and during the third 32.7 to 2.5. In case of DLQI the mean scores decrease from 18 to 2.1 in the first cycle, from 16.9 to 1.9 in the second and from 18.6 to 1.1 in the third. Our study confirmed that omalizumab is an effective medicine in a long-term treatment which improves a physical as well as psychological condition of the patients with antihistamine-resistant CSU. To our knowledge, it is the first study in Poland that presents omalizumab effectiveness during three courses of treatment.

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials

Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. Novartis Pharma.

47 Bilastine in refractory chronic spontaneous urticaria: disease control and cytokine modulation in an open-label prospective study

47 Bilastine in refractory chronic spontaneous urticaria: disease control and cytokine modulation in an open-label prospective study

Comparative analysis of clinical efficacy and safety of omalizumab biosimilar in the treatment of patients with chronic spontaneous urticaria

BACKGROUND: Importance of optimizing strategy for treatment of chronic spontaneous urticaria is highly becoming relevance for the clinicians. Nowadays monoclonal antibodies are preferred option of treatment the refractory chronic spontaneous urticaria, main of that is omalizumab.&#x0D; AIM: to establish comparative analysis of the efficacy and safety of Genolair (JSC Generium, Russia) and Xolair (Novartis Pharma AG, Switzerland) in the treatment of patients with chronic spontaneous urticaria.&#x0D; MATERIALS AND METHODS: A 36-week, open parallel-group study was conducted. Were included 43 adult patients with chronic spontaneous urticaria who were resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines. All patients were divided into 2 groups: the main group (MG; n=18) ― patients who administrated Genolair; the comparison group (CG; n=25) ― patients who firstly administrated Xolair and then switching therapy to Genolair. Throughout the study period, patients completed questionnaires on the assessment of disease activity (UAS 7), urticaria control (UCT), quality of life index (DLQI). Additionally, the level of total IgE in blood serum was assessed. For statistical data processing, EXCEL 2010 and STATISTICA 7.0 software packages were used.&#x0D; RESULTS: After 4 weeks from the start of monoclonal antibody therapy, patients in both groups were responders to omalizumab. At the same time, there were no significant differences when comparing scores on the UAS 7, UCT scale between patients of the MG and the CG during the entire observation period (p 0.05). The change in treatment paradigm in CG also did not have a statistically significant effect on the indicators of urticaria activity and disease control (p 0.05). At the same time, the quality of everyday life changed more positively in the MG, which was reflected in a more pronounced change in the DLQI index at the time of the control assessment since 20 weeks of therapy (p=0.032). An increase in the level of total IgE in the blood serum of all patients with chronic spontaneous urticaria after the initiation of a course of immunobiological therapy was demonstrated, while there were no statistically significant intergroup differences in relation to changes in this laboratory parameter (p 0.05).&#x0D; CONCLUSION: During the treatment of patients with severe chronic spontaneous urticaria, resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines, comparable clinical efficacy and safety of the study drug Genolair and the reference drug Xolair were shown.

The challenge of omalizumab refractory chronic spontaneous urticaria and the relevance of suspecting Schnitzler syndrome without monoclonal gammopathy

Introduction: Schnitzler syndrome (SchS) is a rare autoinflammatory syndrome characterized by chronic urticaria and monoclonal gammopathy (MG). Clinical cases without monoclonal gammopathy have been recorded. Clinical Case: We report on the case of a 43-year-old female with chronic spontaneous urticaria refractory to omalizumab (OMZ) despite a dosage increase (600 mg/4 weeks). Additionally, she developed asthenia and episodes of arthralgias and fever predominantly in the evening. Laboratory re-evaluation revealed elevated inflammatory parameters and skin biopsy showed neutrophilic infiltration. Although MG was absent, SchS was the most likely diagnosis, as other differential diagnoses were excluded. Treatment was started with anakinra, with complete resolution of symptoms. Conclusion: We highlight the importance of specialized urticaria clinics and of reassessing the diagnosis in patients with refractory chronic urticaria. An autoinflammatory disease, such as SchS, could be the diagnosis, even without the presence of monoclonal gammopathy.

In-Vitro Evaluation of Immunomodulation Effects of Mesenchymal Stem Cell-Derived Exosomes in Refractory Chronic Spontaneous Urticaria

In-Vitro Evaluation of Immunomodulation Effects of Mesenchymal Stem Cell-Derived Exosomes in Refractory Chronic Spontaneous Urticaria

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment

BackgroundThe course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. ObjectiveOur aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. MethodsUrticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. ResultsThe authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). Study limitationsThe small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. ConclusionFear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

Existing and Investigational Medications for Refractory Chronic Spontaneous Urticaria: Safety, Adverse Effects, and Monitoring

Treatment of chronic spontaneous urticaria (CSU) is responsive to H1 antihistamines administered up to four times the recommended US Food and Drug Administration dose in approximately 50% of patients. However, when patients do not respond to these first-line agents, evidence-based guidelines using Grading of Recommendations, Assessment, Development, and Evaluations methodology have provided direction for second- and third-line treatments that can effectively treat patients with CSU. Some patients remain refractory to these advanced treatments; therefore, alternative treatments with a lower certainty of evidence may be necessary. Regardless of the therapies used to treat CSU patients, it is essential for clinicians to be knowledgeable about the mechanism of action, efficacy, and safety and monitoring recommendations of the treatments prescribed. This review provides a comprehensive review of the adverse effects and monitoring recommendations for agents in use for CSU treatment as well as those currently undergoing investigation for CSU treatment.

Effectiveness of Hydroxychloroquine and Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study

Chronic spontaneous urticaria (CSU) not controlled by optimized doses of antihistamines is referred to as refractory CSU. Add-on therapies recommended by guidelines include omalizumab, immunosuppressive, and anti-inflammatory agents. The objective of the study was to assess the real-world effectiveness of different add-on treatment options for refractory CSU in 2 large clinical practices. A retrospective chart review was conducted in 264 patients with refractory CSU not adequately controlled for ≥6 weeks with optimized doses of second-generation histamine-1 blockers. Omalizumab and hydroxychloroquine were the most frequently prescribed add-on therapies, allowing comparisons of clinical outcomes for these 2 agents. Complete response included absent or infrequent urticaria and patient satisfaction with treatment. Partial response was reduced hives, but requiring a second add-on therapy. Sustained response was complete response to an add-on therapy for ≥1 year. Omalizumab add-on treatment was significantly more likely to be associated with a complete response versus hydroxychloroquine. Complete sustained response at 1 year was observed in 82% (111 of 134) of patients on omalizumab and 66% (73 of 111) on hydroxychloroquine as the first add-on therapy (P < .01). Patients with thyroid disease had a poorer response to add-on treatments (45% responded vs 63%; P= .03). In patients with incomplete responses to first add-on interventions (n= 45), 65% and 62% subsequently had complete responses to omalizumab and hydroxychloroquine, respectively. Although omalizumab was superior, hydroxychloroquine achieved a complete response in two-thirds of treated patients. Given a favorable safety profile, hydroxychloroquine should be considered as an add-on treatment for refractory CSU.

Monoclonal Antibodies in Treating Chronic Spontaneous Urticaria: New Drugs for an Old Disease

Background: H1-antihistamines (H1AH) represent the current mainstay of treatment for chronic spontaneous urticaria (CSU). However, the response to H1AH is often unsatisfactory, even with increased doses. Therefore, guidelines recommend the use of omalizumab as an add-on treatment in refractory CSU. This paved the way for the investigation of targeted therapies, such as monoclonal antibodies (mAbs), in CSU. Methods: A literature review was conducted including papers published between 2009 and 2022 and ongoing trials about the efficacy and safety of mAbs as treatment for CSU. Results: Twenty-nine articles, a trial with preliminary results, and seventeen ongoing or completed clinical trials on the use of mAbs in CSU were included. Randomized controlled trials (RCTs), meta-analysis, and real-life studies have proven the effectiveness and safety of omalizumab as a third-line treatment in refractory CSU. However, a percentage of patients remain unresponsive to omalizumab. Therefore, other mAbs, targeting different pathways, have been used off-label in case series and others are under investigation in RCTs. Most of them have showed promising results. Conclusions: Omalizumab remains the best choice to treat refractory CSU. Although results from other mAbs seem to be encouraging to achieve symptom control in refractory CSU, thus improving patients’ QoL, RCTs are needed to confirm their effectiveness and safety.

Omalizumab for the management of refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a heterogeneous, systemic, primarily mast cell-driven disease with sudden appearance of wheals with or without angioedema with pruritus for more than 6 weeks. It affects 0.3%–0.6% of the general population. CSU is a complex immune-mediated disease due to induction of basophil and mast cell degranulation with more than one mechanism of auto-allergy Type I (mediated by specific immunoglobulin E (IgE) targeting auto-allergens as thyroperoxidase, etc.) and auto-immunity Type II (mediated by IgG auto-antibodies binding to alpha-subunit of high affinity IgE receptor [FcERI]) with increased expression of Type II cytokines and activation of coagulation cascade. Pruritus is due to sensory nerve activation by histaminergic pathway (Histamine receptors- H1R and H4R) and histamine-independent pathway (Substance P, Capsacin, and Reactive oxygen species, etc.). The international guidelines on CSU recommend to treat CSU until it is gone. The use of second-generation anti-histamine in effective dose as the first-line treatment and up-dosing of second generation (SgAH) up to four-fold is recommended in treatment-resistant patients. The humanized anti-IgE monoclonal antibody Omalizumab has been shown to have both excellent safety profiles as the only third-line treatment option in anti-histamine-resistant urticaria (approved by United States Food and Drug Administration in August, 2014). However, there are several questions to be answered with reference to the optimal dose, duration, and the rates of long-term remission with omalizumab. Other biologics as Ligelizumab are less well studied but have an important role in the specific type of omalizumab-resistant CSU. In this review, we will summarize the role of omalizumab in anti-histamine resistant CSU.

Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey.

The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU in clinical practice. A study-specific questionnaire was administered to a group of physicians (N.=21) with a specialist interest in CSU from different areas of Italy (group A) and also to other physicians (N.=25) who manage CSU only occasionally in their clinical activity (group B). In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

Efficacy and safety of omalizumab in Chinese patients with anti‐histamine refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous development of wheals, itching, and/or angioedema, for ≥6 weeks. In China, non‐sedating H1‐antihistamines (H1AH) are the recommended first‐line treatment, with escalation up to 4× the standard dose in symptomatic patients to achieve control. Treatment options for Chinese patients who remain symptomatic on H1AH treatment are limited. This 20‐week randomized, double blind, placebo‐controlled, parallel‐group study investigated the efficacy and safety of omalizumab as an add‐on therapy for the treatment of patients with CSU who remained symptomatic despite H1AH treatment in China. Adult patients (N = 418) diagnosed with refractory CSU for ≥6 months were randomized (2:2:1) to receive omalizumab 300 mg (OMA300), omalizumab 150 mg (OMA150) or placebo, subcutaneously, every 4 weeks. Primary outcome was change from baseline to week 12 in weekly itch severity score (ISS7). Safety was assessed by rates of adverse events (AEs). Demographic and disease characteristics at baseline were comparable across treatment groups. At week 12, statistically significant greater decreases from baseline were observed in ISS7 with OMA300 (least square mean difference [LSM]: −4.23; 95% confidence interval [CI]: −5.70, −2.77; p < 0.001) and OMA150 (LSM: −3.79; 95% CI: −5.24, −2.33; p < 0.001) versus placebo. Incidence of treatment‐emergent AEs over 20 weeks was slightly higher with OMA300 (71.3%) compared to OMA150 and placebo groups (64.7% and 63.9%, respectively). The incidences of serious AEs were balanced between groups. This study demonstrated the efficacy and safety of omalizumab in Chinese adult patients with CSU who remained symptomatic despite H1AH therapy.

Treating chronic urticaria refractory to H1-antihistamines in Russia: data from the AWARE study.

IntroductionData on burden and treatment outcomes of chronic spontaneous urticaria (CSU) in Russia are limited. Poor adherence to recommended treatments can lead to suboptimal management of CSU patients.AimTo understand disease burden, treatment algorithms, and outcomes of CSU in the Russian cohort of the AWARE study.Material and methodsAWARE was a global prospective, non-interventional study of chronic urticaria in the real-world setting. Adult patients with H1-antihistamines (H1AH)-refractory CSU for ≥ 2 months were included. Disease characteristics, quality of life (QoL), healthcare resource utilisation (HRU), and pharmacological treatments were observed during the 2-year study period.ResultsOf the 135 patients enrolled from Russia, 121 completed the study. Pre-baseline, ~37% of patients were managed with non-recommended treatments (33% treated with sedative H1AH; 4% with other non-recommended treatments) and 28.2% of patients were not treated for CSU. There was a reduction in the use of sedative H1AH during the study (0.9% of patients treated with sedative H1AHs at Year 2). Decreased disease activity was seen as early as 3 months and continued to improve over 2 years (Urticaria Activity Score over 7 days (UAS7): 20.2 at baseline (n = 124) to 10.1, 7.1, and 3.2 at month 3 (n = 118), 12 (n = 109), and 24 (n = 109), respectively). This corresponded with QoL improvements (dermatology life quality index (DLQI) score: 10.3 at baseline to 5.4, 3.6, and 2.3 at Month 3 (n = 75), 12 (n = 98), and 24 (n = 92), respectively), and reduced angioedema and hives throughout the study.ConclusionsThe burden of CSU in Russia is high, contributing to increased HRU. Guideline-recommended treatments and systematic escalation of therapy to achieve complete symptom control can improve management of patients with CSU.