Ligelizumab for Chronic Spontaneous Urticaria Maurer, Marcus; Giménez-Arnau, Ana M; Sussman, Gordon ...
The New England journal of medicine,
10/2019, Letnik:
381, Številka:
14
Journal Article
Recenzirano
Odprti dostop
This dose–response trial of ligelizumab showed that approximately half the patients treated with 240 mg of ligelizumab had complete resolution of hives, as compared with only approximately one ...quarter of the patients treated with the recommended dose of omalizumab.
The capillary system immediately responds to many pathologies and environmental conditions. Accurate monitoring of its functioning often enables early detection of various diseases related to ...disorders in skin microcirculation. To expand the scope of capillaroscopy application, it is reasonable to visualize and assess blood microcirculation exactly in the areas of inflamed skin. Body vibrations, breathing, non-flat skin surface and other factors hamper the application of conventional capillaroscopes outside the nailfold area. In this paper, we propose an exoscope-based optical system for high-quality non-invasive computational imaging of capillary network in various areas of the body. Accurate image matching and tracking temporal intensity variations allow detecting the presence of blood pulsations, precise mapping of capillaries and photoplethysmogram acquisition. We have demonstrated the efficiency of the proposed approach experimentally by
mapping and analysis of microvessels in wrist, forearm, upper-arm, breast and hip areas. We believe that the developed system will increase the diagnostic value of video capillaroscopy in clinical practice.
Introduction Data 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. Aim: To understand disease burden, treatment algorithms, and outcomes of CSU in the Russian cohort of the AWARE study. Material and methods AWARE 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. Results Of 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. Conclusions The 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.
Ligelizumab for Chronic Spontaneous Urticaria Maurer, Marcus; Giménez-Arnau, Ana M.; Sussman, Gordon ...
New England journal of medicine/The New England journal of medicine,
10/2019, Letnik:
381, Številka:
14
Journal Article
Autoimmune chronic spontaneous urticaria (aiCSU) comes with high disease activity and poor response to treatment. Recently, elevated levels of IgG anti-thyroid peroxidase (aTPO) and low levels of ...total IgE were reported to be common in aiCSU.
To investigate how high aTPO and low IgE individually and combined are linked to features of aiCSU, including treatment responses.
We analyzed records of patients with CSU from 2 independent cohorts (n = 1120) for demographic, clinical, and laboratory parameters and treatment responses. Total IgE and aTPO were measured, and 4 markers of aiCSU were analyzed: autologous serum skin test, basophil activation test (BAT), and blood eosinophil and basophil counts. Cutoff values were greater than or equal to 34 kU/L (high aTPO) and less than 40 IU/mL (low total IgE).
One of 10 patients with CSU had both high aTPO and low IgE (aTPO↑IgE↓, 11%, n = 123). aTPO↑IgE↓ was linked to higher age at CSU onset, being female, angioedema, and shorter CSU duration. aTPO↑IgE↓ was associated with markers of aiCSU, that is, BAT and autologous serum skin test positivity, basopenia, and eosinopenia (P < .01 for all). Almost half the patients with aTPO↑IgE↓ (44%, 19 of 43) had a positive BAT result, the best single marker for aiCSU, versus 12% (43 of 344) of patients without aTPO↑IgE↓ (P < .001). Relative risk of showing BAT positivity for a patient with aTPO↑IgE↓ is 3.636 (95% CI, 2.382-5.551). Patients with aTPO↑IgE↓ showed low response rates to antihistamine treatment as compared with patients without aTPO↑IgE↓ (30% vs 47%; P = .01).
Our findings suggest that aTPO↑IgE↓ is a useful diagnostic marker for aiCSU in everyday clinical practice.
Background
Ligelizumab, a next‐generation, humanized anti‐immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms ...are inadequately controlled with standard‐of‐care therapy.
Objective
To evaluate the long‐term safety and re‐treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study.
Methods
This open‐label, single‐arm, long‐term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose‐finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post‐treatment for 48 weeks.
Results
Overall, ligelizumab was well‐tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment‐emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks.
Conclusion
The long‐term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re‐treatment efficacy was shown.
Trial Registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.
A total of 226 patients received ligelizumab 240 mg for 52 weeks. Overall, 84.1% of patients experienced at least one TEAE. After 52 weeks of treatment, 53.1% of patients had a complete response and 75.8% of patients had cumulative complete responses. The long‐term safety profile of ligelizumab 240 mg in patients was consistent with the core study and re‐treatment efficacy was shown.Abbreviations: BAS, basophil; CSU, chronic spontaneous urticaria; FcεRI, Fc epsilon receptor 1; IgE, immunoglobulin E; MC, mast cell; MoA, mechanism of action; TEAE, treatment‐emergent adverse event; UAS7, weekly urticaria activity score; UAS7 = 0, complete response; UAS7 ≤ 6, minimal disease activity
Display omitted
Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may ...occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment.
We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE).
The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022).
The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms.
The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.
Background
Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown.
Aim
...To analyze the course and features of CU during and after pregnancy.
Patients and methods
PREG‐CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47‐item questionnaire completed by CU patients, who became pregnant within the last 3 years.
Results
A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively.
Conclusions
These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy.
During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged; rate of angioedema decreased from 38.2% to 17.4%. CU exacerbations occurred most commonly in the third trimester (27.6%) or in the first trimester (22.8%). Of the patients whose urticaria improved during pregnancy, 50% experienced worsening after giving birth, whereas 33.6% and 16.4% reported no change. Abbreviations: CIndU, chronic inducible urticaria; CU, chronic urticaria; PREG‐CU, Pregnancy and Chronic Urticaria; UCARE, Urticaria Centers of Reference and Excellence
Background
Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease.
Objective
To analyse the treatment use by CU ...patients before, during and after pregnancy as well as outcomes of pregnancy.
Methods
PREG‐CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence network. Data were collected via a 47‐item‐questionnaire completed by CU patients who became pregnant during their disease course.
Results
Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication including standard‐dose second generation H1‐antihistamines (35.1%), first generation H1‐antihistamines (7.6%), high‐dose second‐generation H1‐antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new‐borns were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth.
Conclusion
Most CU patients used treatment during pregnancy especially second‐generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new‐borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy.
PDF
