Dual biologics therapy in a patient with severe asthma and chronic urticaria: a case report and review of the literature.

INTRODUCTION: The data on the use of dual biologics are scant, but a topic of current interest. CASE STUDY: In this report, the treatment regimen of a patient with two T helper 2 pathway-related comorbidities, severe asthma, and chronic spontaneous urticaria, was presented. RESULTS: Both urticaria and asthma symptoms of the patient could not be controlled entirely with monotherapy while both diseases could be controlled after omalizumab-mepolizumab dual treatment. No adverse events were observed after 6 months of dual biologics use. CONCLUSION: This report supports other publications in the literature involving the use of dual biologics and provides a summary of the literature.

Inhibition of KIT for chronic urticaria: a status update on drugs in early clinical development.

INTRODUCTION: Chronic urticaria (CU), including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), is a prevalent, enduring, mast-cell driven condition that presents challenges in its management. There is a clear need for additional approved treatment options beyond H1 receptor antagonists and the anti-IgE monoclonal antibody (mAb), omalizumab. One of the latest therapeutic strategies targets KIT, which is considered the primary master regulator for mast cell-related disorders. AREAS COVERED: This review provides a status update on KIT inhibiting drugs in early clinical development for CU. EXPERT OPINION: Whereas multi-targeted tyrosine kinase KIT inhibitors carry the risk of off-target toxicities, initial data from anti-KIT mAbs indicate significant potential in CSU and CIndU. The prolonged depletion of mast cells over several weeks by barzolvolimab could effectively control urticarial symptoms. Regarding safety, based on theoretical considerations and the available preliminary results, it is already evident that there may be more side effects compared to omalizumab. However, long-term safety data beyond 12 weeks are still lacking. The outcome of ongoing or planned clinical trials with several anti-KIT mAbs will need to demonstrate benefits compared to anti-IgE in CU or whether one approach is better suited for specific urticaria endotypes.

Comparing four immunosuppressive agents for chronic spontaneous urticaria-A network meta-analysis.

BACKGROUND: Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents. OBJECTIVE: The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU. METHODS: PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects. RESULTS: This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples. CONCLUSION: Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.

Biomarkers for Monitoring Treatment Response of Omalizumab in Patients with Chronic Urticaria.

Chronic urticaria (CU) is a debilitating skin disease affecting around 1% of the population. CU can be subdivided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Different pathophysiological mechanisms have been proposed to play a role in the development of CU, and these are also being investigated as potential biomarkers in the diagnosis and management of the disease. As of now the only assessment tools available for treatment response are patient reported outcomes (PROs). Although these tools are both validated and widely used, they leave a desire for more objective measurements. A biomarker is a broad subcategory of observations that can be used as an accurate, reproducible, and objective indicator of clinically relevant outcomes. This could be normal biological or pathogenic processes, or a response to an intervention or exposure, e.g., treatment response. Herein we provide an overview of biomarkers for CU, with a focus on prognostic biomarkers for treatment response to omalizumab, thereby potentially aiding physicians in personalizing treatments.

The Role of Adjuvant Therapy in the Management of Chronic Urticaria. / [Artículo traducido] El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea.

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitaminD, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.

PK/PD modeling to characterize placebo and treatment effect of omalizumab for chronic spontaneous urticaria.

The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous urticaria, which could elucidate its pathogenesis and treatment response. This study has two objectives; (1) characterize the population PK of omalizumab and its PD effect on IgE, and (2) develop a drug effect model of omalizumab in urticaria (via change in weekly itch severity score). The target-mediated population of PK/PD model incorporating omalizumab-IgE binding and turnover adequately described PK and PD of omalizumab. The effect compartment model and linear drug effect and additive placebo response adequately described placebo and treatment effects of omalizumab. Several baseline covariates were identified for PK/PD and drug effect models. The developed model has the potential to aid in understanding variability in PK/PD as well as response to omalizumab treatment.

The Role of Adjuvant Therapy in the Management of Chronic Urticaria.

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.

Differences between adult and pediatric chronic spontaneous urticaria from a cohort of 751 patients: Clinical features, associated conditions and indicators of treatment response.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common disease both in the pediatric and in the adult population. However, there are differences between the two patient populations with respect to etiological factors, comorbidities, and treatment responses. Our aim was to determine differences between pediatric and adult CSU in terms of clinical characteristics, laboratory parameters, comorbidities, response to treatment, and indicators of response. METHODS: A retrospective analysis of CSU patients was performed. Data regarding differences between pediatric and adult CSU patients were analyzed. Indicators of treatment response were determined separately in both pediatric and adult patients. RESULTS: Of 751 CSU patients (162 pediatrics and 589 adults), female dominancy (48.8% vs. 69.6%) and rate of angioedema (19.1% vs. 59.8%) were lower, and disease duration (5 months vs. 12 months) was shorter in pediatric patients. Anti-TPO positivity (24.7% vs. 9%), elevated CRP (46.5% vs. 11.1%), eosinopenia (38.5% vs. 18.1%), and skin prick test positivity (39.3% vs. 28.8%) were significantly more frequent in adult patients. Response to antihistamines was higher in the pediatric group, and only 7% used omalizumab versus 20.8% in the adults. The comparisons were also performed between <12-year and ≥12-year patients and yielded similar results. CONCLUSION: Pediatric CSU shows distinct characteristics such as lower incidence of angioedema and antithyroid antibodies, and it responds better to antihistamines. These suggest that CSU becomes more severe and refractory in adolescents and adults. Adolescent CSU shows features similar to adult CSU rather than pediatric CSU.

Chronic spontaneous urticaria after BNT162b2 mRNA (Pfizer-BioNTech) vaccination against SARS-CoV-2.

Background: The factors that trigger and exacerbate chronic spontaneous urticaria (CSU) are well known, but it is not unclear whether messenger RNA (mRNA) vaccination against severe acute respiratory syndrome coronavirus 2 can trigger new cases of CSU or a relapse of CSU after long-term remission. Objective: To study the clinical cases of patients with new-onset CSU and CSU in remission who relapsed within 3 months after BNT162b2 mRNA vaccination. Methods: All patients with a CSU diagnosis within 12 weeks of BNT162b2 mRNA vaccination were retrospectively identified and included in the new-onset CSU and the relapsed CSU groups. The first control group (CSU control group) retrospectively consisted of patients diagnosed with CSU in complete clinical remission for ≥ 6 months, with no CSU relapse after vaccination. The second control group (healthy control group) consisted of subjects who were fully vaccinated and without CSU, matched 1:2 for age and sex with patients with CSU. Results: Twenty-seven patients were included in the relapsed CSU group, 32 patients in the new-onset CSU group, 179 patients in the CSU control group, and 476 subjects in the healthy control group. The relapsed CSU and new-onset CSU groups had more allergic comorbidities overall (19 [70.4%] and 13 [40.6%], respectively) than the CSU control group and the healthy control group (50 [27.9%] and 110 [23.1%], respectively; p < 0.001). Multiple logistic regression analysis showed that a positive autologous serum skin test result, overall allergic comorbidities, and basopenia were positively associated with the probability of CSU relapse within 3 months after BNT162b2 mRNA vaccination (odds ratio [OR] 5.54 [95% confidence interval {CI}, 2.36-13.02], p < 0.001); OR 6.13 [95% CI, 2.52-14.89], p = 0.001; and OR 2.81 [95% CI, 1.17-6.72, p = 0.020, respectively). Conclusion: It is possible that BNT162b2 mRNA vaccination serves as a provoking and/or relapsing factor of CSU in individuals with allergic diseases and/or predisposed autoimmunity.