Omalizumab In Chronic Spontaneous Urticaria Research Articles

Predicting the Speed of Response to Omalizumab in Chronic Spontaneous Urticaria

Introduction: Two distinct chronic spontaneous urticaria (CSU) endotypes, IgE-mediated autoallergic and IgG-mediated autoimmune, were defined based on the response patterns to omalizumab. However, the coexistence of IgE and IgG autoantibodies in a subset of patients might complicate the prediction of the treatment outcomes. This study aimed to evaluate the effectiveness and safety of omalizumab in CSU patients, focusing on the factors predicting the response patterns. Methods: This was a retrospective cross-sectional single-center study investigating CSU patients treated with omalizumab for at least 6 months between September 2015 and February 2023. Patients were evaluated regarding demographics, clinical findings, baseline laboratory parameters, treatment outcomes, and side effects. Early and late responders were defined depending on the time for response, within or after 3 months, respectively. Results: Among 82 patients, 75 (91.5%) responded to omalizumab during the first 6 months, classified as early (n = 51) and late responders (n = 24). The IgG anti-thyroid peroxidase (anti-TPO)/total IgE ratio was an independent predictor for determining the speed of response (p < 0.05). Of 29 patients who discontinued omalizumab, 19 (65.5%) experienced relapse with a good response to retreatment (n = 18/19, 94.7%). Early responders relapsed more frequently than late responders (77.3% vs. 28.6%) (p < 0.05). Only mild side effects were observed in a minority of patients (n = 8/82, 9.8%). Conclusion: Omalizumab is an effective and safe treatment in CSU. The IgG anti-TPO/total IgE ratio seems a valuable tool to predict the early and late responders, the former having a higher possibility of relapse upon drug withdrawal.

Comment on Manzoor, H. et al. Efficacy of Different Dosing Regimens of IgE Targeted Biologic Omalizumab for Chronic Spontaneous Urticaria in Adult and Pediatric Populations: A Meta-Analysis. Healthcare 2022, 10, 2579.

In December 2022, the paper "Efficacy of Different Dosing Regimens of IgE Targeted Biologic Omalizumab for Chronic Spontaneous Urticaria in Adult and Pediatric Populations: A Meta-Analysis" was published in the Healthcare journal [...].

Mapping the intellectual structure of the research of omalizumab in chronic spontaneous urticaria: A bibliometric analysis

BackgroundGuidelines for treating Chronic Spontaneous Urticaria (CSU) recommend using the IgE-targeted biologic Omalizumab in patients with antihistamine-refractory disease. ObjectiveTo present a bibliometric review of publications related to Omalizumab and CSU over the past two decades. MethodsPublications that are relevant from 2003 to 2022 were extracted from the Science Citation Index-Expanded (SCI-EXPANDED) in the Web of Science Core Collection (WoSCC) database as of January 8, 2023. We utilized CiteSpace (version 6.1.R3), VOSviewer (version 1.6.18), and the R package (version 4.2.1) to analyze and visualize the data. The R package bibliometrix (version 4.2.1) was also used. ResultsBetween 2003 and 2022, a total of 566 articles were published. Since 2014, there has been a rapid increase in publication outputs. According to the collaboration network, the most influential country/institute/scholar was the USA, Charité Universitätsmedizin Berlin, and Maurer Marcus, respectively. The study identified the Journal of Allergy and Clinical Immunology: In Practice as the most productive journal and the Journal of Allergy and Clinical Immunology as the most co-cited journal. The analysis of keywords revealed that high-frequency terms such as angioedema, IgE, treatment, anti-IgE, asthma, and atopic dermatitis were present. Moreover, recent studies in this area have mainly concentrated on biomarkers, Dupilumab, and COVID-19. ConclusionThere has been a growing interest in the use of Omalizumab in CSU in recent years. The current trending topics in this research are the identification of biomarkers and the development of new monoclonal antibodies for the treatment of CSU.

Comparative efficacy of ligelizumab versus omalizumab in chronic spontaneous urticaria

Comparative efficacy of ligelizumab versus omalizumab in chronic spontaneous urticaria

Interleukin-33, endothelin-1, and inflammatory parameters in chronic spontaneous urticaria

Background: Endothelin-1 (ET-1) and interleukin-33 (IL-33) can modulate the activation of mast cells and basophils in the pathophysiology of allergic diseases, interplaying with other mediators of “low-grade inflammation.” Objective: To compare ET-1, IL-33, the neutrophil-lymphocyte ratio (NLR), eosinophil-lymphocyte ratio (ELR), platelet-lymphocyte ratio (PLR), eosinophil-basophil ratio (EBR), systemic immune inflammation index (SII), and system inflammation response index (SIRI) in patients with chronic spontaneous urticaria (CSU) and are antihistamine sensitive (AHS), antihistamine resistant (AHR), omalizumab sensitive (OmS), and omalizumab resistant (OmR). Methods: A prospective observational study enrolled 68 consecutive patients with CSU diagnosed and managed according to the dermatology section of the European Academy of Allergology and Clinical Immunology (EAACI), the European Union funded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization guidelines. Patients with a urticaria control test score of &gt;12 are considered treatment sensitive, and ≤ 12 are considered resistant. The control group consisted of 20 sex-matched subjects without urticarial diseases. Total immunoglobulin E (IgE), antinuclear antibodies (ANA), thyroid stimulating hormone, antithyroid peroxidase, mean platelet volume (MPV), NLR, ELR, PLR, EBR, SII, SIRI, ET-1, and IL-33 were measured at the study entry and compared between the study groups. Results: Thirty AHS group, 38 AHR group, and 20 control group patients were included. The AHS, AHR, and control groups did not differ in demographic parameters, but the CSU groups were characterized by higher indicators of inflammation. In comparison with the AHS group, the AHR group was characterized by higher levels of IL-33 (p = 0.007), ET-1 (p = 0.032), C-reactive protein (p = 0.016), MPV (p = 0.002), and higher rates of positive ANA (p = 0.019). Of the 38 patients from the AHR group, 30 (79%) were included in the OmS group and 8 (21%) were included in the OmR group. The OmR group was characterized by higher levels of C-reactive protein (p = 0.022), EBR (p &lt; 0.001), higher rates of ANA (p = 0.004), and lower levels of ET-1 (p = 0.025) than the OmS group. Conclusion: Our study did not confirm NRL, PRL, SII, and SIRI, PLR as the biomarkers of treatment response to antihistamines and/or omalizumab in CSU. Higher blood levels of IL-33 and ET-1 characterize AHR CSU.

Elevated baseline soluble FcεRI may be linked to early response to omalizumab treatment in chronic spontaneous urticaria.

Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment in chronic spontaneous urticaria (CSU). Predictors of fast and good response for omalizumab treatment have not yet been identified and characterized. To evaluate whether soluble FcεRI (sFcεRI), a marker of IgE-mediated mast cell activation, predicts the time of response to omalizumab in CSU. Sera of 67 CSU patients were obtained before omalizumab treatment and analysed for sFcεRI levels by ELISA (2 ng/mL was used as cut-off for elevated sFcɛRI). Treatment response during the first 4 weeks was assessed with the urticaria activity score (UAS7), urticaria control test (UCT) and the rolling UAS7 (rUAS7). Elevated pre-treatment sFcɛRI levels were detected in more than 70% of patients with completely controlled disease (UCT = 16) and well-controlled disease (UCT = 12-15) and were significantly associated with disease control (χ2 = 4.94, p < 0.05). More than half of the patients (14/25) with low levels had poor disease control (UCT < 12). Of the patients who achieved complete and marked UAS7 response, respectively, 75% and 63% had elevated baseline sFcɛRI levels. Post-treatment UAS7 scores were lower in patients with elevated sFcɛRI levels reaching statistical significance at Week 3 (p < 0.05). Patients with elevated baseline sFcɛRI levels achieved rUAS7 ≤ 6 and = 0 earlier than those with lower levels (Days 9 vs. 13 and Days 12 vs. 14, respectively). Elevated sFcεRI serum levels predict early and good response to treatment with omalizumab, which may help to better design treatment options for CSU patients.

Omalizumab in Chronic Spontaneous Urticaria (CSU): Real-Life Experience in Dose/Interval Adjustments and Treatment Discontinuation.

Data on real-life experience with omalizumab dose/interval adjustments are still limited, as well as on omalizumab discontinuation. To evaluate efficacy and safety of omalizumab dose/interval adjustment in a Portuguese cohort of patients with chronic spontaneous urticaria (CSU) and to characterize those who discontinued omalizumab. A retrospective study of patients who started omalizumab for CSU at a Portuguese Urticaria Center of Reference and Excellence (UCARE) was conducted between 2009 and 2021. Response criteria were based on a weekly Urticaria Activity Score (UAS7) <7 points (partial: UAS7 7-15 points; nonresponders: UAS7 >15 points) and minimal important difference >10 points. A total of 138 patients were enrolled in the study; 83% of them were women, and the median age was 49 years (interquartile range: 40-58 years). On 300 mg q4 weeks, 96 (70%) patients were responders, 29 (21%) partial responders, and 13 (9%) nonresponders. After dose/interval adjustments (up to 600 mg q2 weeks), 108 (78%) were responders, 27 (20%) partial responders, and 3 (2%) nonresponders. No adverse events were reported. Updosing was more frequent in patients with angioedema, body mass index >30 kg/m2, positive basophil activation test, and autologous serum test. A total of 71 (51%) patients lengthened interval, presenting higher median pre-omalizumab D-dimer (0.2 vs 0 mcg/mL, P= .038) and C-reactive protein (0.3 vs 0.1 mg/dL, P= .030) values than those with a standard dose. In total, 37 patients (27%) stopped omalizumab, but 14 (38%) of them needed retreatment on average 11 months after discontinuation. Patients with angioedema and a longer omalizumab duration had higher chance of relapse. Omalizumab dose and/or interval adjustment is effective and safe and should be implemented in partial/nonresponders for response improvement and in responders for further discontinuation. A protocol for regimen adjustments is proposed.

Association Between Serum Total IgE Levels and Clinical Response to Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab. We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU. PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis. Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings. This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.

Chronic Urticaria Treatment with Omalizumab-Verification of NLR, PLR, SIRI and SII as Biomarkers and Predictors of Treatment Efficacy.

Biomarkers that are able to predict the response to omalizumab (OMA) in chronic spontaneous urticaria (CSU) are highly valued. The aim of our study was to evaluate the UAS7 (urticaria activity score assessed for 7 days), DLQI (dermatology life quality index), SII (systemic immune-inflammation index), SIRI (systemic inflammation response index), PLR (platelet/lymphocyte ratio) and NLR (neutrophil/lymphocyte ratio) in a group of 46 CSU a patients treated for 24 weeks with OMA (300 mg every 4 weeks). There were no statistically significant differences observed at the start nor at the end of the treatment between the two groups (responders vs. non-responders) and SII, SIRI, PLR and NLR. However, a statistically significant correlation was observed between severity of urticaria expressed in UAS7 scores and the quality of life (evaluated by DLQI). Furthermore, at week 24, both groups demonstrated significant improvement in quality of life. Our single center study did not confirm the usefulness of SII, SIRI, NLR or PLR as predictors of the response to OMA in CSU. However, it is of importance that even patients who did not respond to the treatment presented a significant improvement in quality of life. Additionally, we also observed that the efficacy of treatment was unchanged amongst patients who underwent a second series of treatment in cases of relapse.

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.

Predictors of response to omalizumab in chronic spontaneous urticaria

Predictors of response to omalizumab in chronic spontaneous urticaria

IgG and IgE Autoantibodies to IgE Receptors in Chronic Spontaneous Urticaria and Their Role in the Response to Omalizumab

Background: Chronic spontaneous urticaria (CSU) is defined as the recurrence of unprovoked transient wheals and itch for more than 6 weeks. Currently, there is an unmet need concerning response prediction in CSU. The present study investigated biomarkers of type I and type IIb autoimmunity as potential predictors of response to omalizumab in CSU. Materials and methods: Differences in levels of IgG and IgE autoantibodies targeting the high- and low-affinity IgE receptors (FcεRI and FcεRII, respectively), as well as spontaneous and specifically triggered leukotriene C (LTC)4 release by basophils from the investigated subjects, were evaluated in 18 consecutive, prospectively enrolled CSU patients and 18 age- and sex-matched, healthy non-atopic controls. Results: The patients with CSU had higher levels of anti-FcεRI IgE (542 (386.25-776.5) vs. 375 (355-418), optical density (OD), p = 0.008), and IgG (297 (214.5-431.25) vs. 193.5 (118-275) OD, p = 0.004) autoantibodies relative to the controls. Simultaneous anti-FcεRI IgG and IgE positivity (i.e., both autoantibody levels above the respective cut-offs) was recorded only in late- and non-responders (3/8 and 1/2, respectively). Discussion: Significantly higher anti-FcεRI IgE autoantibody levels were found in the CSU patients as compared to the controls, supporting FcεRI as an autoallergic target of IgE (autoallergen) in the complex pathophysiological scenario of CSU. The co-occurrence of anti-FcεRI IgG and IgE autoantibodies was documented only in late- and non-responders, but not in early ones, crediting the co-existence of autoimmune and autoallergic mechanisms as a driver of late/poor response to omalizumab.

Update on prospective markers of treatment response with omalizumab in chronic spontaneous urticaria

Update on prospective markers of treatment response with omalizumab in chronic spontaneous urticaria

Omalizumab in Chronic Spontaneous Urticaria: Assessment of Response in Twenty-Five Patients

Background Omalizumab is a recombinant humanized monoclonal antibody against immunoglobulin E (IgE). It is approved for the treatment of chronic spontaneous urticaria (CSU) in patients ≥12-years of age. Objective We carried out a retrospective cross-sectional study in 25 patients with CSU to evaluate the characteristics of response of CSU to omalizumab treatment. Method A retrospective cross-sectional study of a convenient sample of all patients diagnosed as CSU who have been using omalizumab treatment during the study period from January 2018 to January 2020 in the Dermatology Department in King Abdulaziz Hospital, Makkah, Saudi Arabia. Results A total of 25 patients have participated in this study. The average age of patients was 40-years. Majority of the patients were female (52.0%, n=15). The average duration of illness was 1.32-years. Majority of the patients (72.0%, n=18) received two courses of omalizumab treatment. Minority of patients (28.0%, n=7) received one course of omalizumab treatment which was statistically significant (p value&lt;0.01). Number of patients who have been using oral 2nd generation antihistamine during the first course and 2nd course was (72%, n=18 out of 25) and (50%, n=9 out of 18) respectively. Number of flare-ups during 2nd course (1.72 flares up per patient, n=31 flare-ups among 18 patients) was less than the number of flares-up during 1st course (2.96 flares-up per patient, n=74 flare-ups among 25 patients) which was statistically significant (p value&lt;0.01). Number of patients who showed no flare-ups during the 1st and 2nd course of omalizumab treatment was (16%, n=4 out of 25 patients) and (27.77%, n=5 out of 18 patients) respectively. The average intensity of flares-up during 2nd course of omalizumab treatment was less than the average intensity of flares-up during first course of omalizumab treatment as the following; during 2nd course ( 33.33%, n=6 out of 18 patients), (27.77% n=5 out of 18 patients), (11.11%, n=2 out of 18 patients) mild, moderate and severe flares-up respectively and the severity during 1st course was (40.0%, n=10 out of 25 patients), (28.0%, n=7 out of 25 patients), (16.0%, n=4 out of 25 patients) mild, moderate and severe flares-up respectively. Conclusion According to expert’s guidelines, CSU of ≥3-years would be treated with omalizumab for a minimum of one-year. In our study, in spite of the short duration of CSU (average duration was 1.32-years), the majority of patients (72.0%, n=18) received omalizumab for 1-year (two courses of omalizumab treatment) suggesting that the majority of patients with CSU in general requires omalizumab ≥1-year. Our study also showed 5 patients who were free of any flare-up and they were not using 2nd generation antihistamines suggesting that omalizumab alone as monotherapy can be effective

Efficacy of Different Dosing Regimens of IgE Targeted Biologic Omalizumab for Chronic Spontaneous Urticaria in Adult and Pediatric Populations: A Meta-Analysis.

Chronic urticaria is a debilitating skin condition that is defined as itchy hives at least twice a week and lasting for six or more weeks, with or without angioedema. Chronic spontaneous urticaria (CSU) is a form of disease that is witnessed in two-thirds of those with chronic urticaria. This meta-analysis explores the efficacy of differential dosages of omalizumab for outcomes of weekly itching scores, weekly wheal scores, urticarial assessment score 7 (UAS7), and responder rates. Adhering to PRISMA Statement 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Embase, and Web of Science was conducted until 15 September 2022. A combination of the following keywords was used: omalizumab and chronic urticaria. Data comprising clinical trial ID, name, author/year, country, dosage and time of intervention, inclusion criteria, mean age, female gender, and racial grouping information were obtained. The meta-analytical outcomes were analyzed in RevMan 5.4. The risk-of-bias assessment was conducted using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). A total of 10 trials comprising 1705 patients with CSU were included. Notably, 1162 belonged to the intervention group, while 543 were controls. A total of 70.4% of the participants were female in the intervention group, while 65.6% of them were female in the control group. The overall mean age was 38.64 ± 10.66 years. Weekly itch score outcomes were most notable with 150 mg dosage (Cohen's d = -2.6, 95% CI = -4.75, -0.46, p = 0.02). The weekly wheal score outcomes had the largest effect size with 300 mg dosage (Cohen's d = -1.45, 95% CI = -2.2, -0.69, p = 0.0002). For UAS7 outcomes, the largest effect size was yielded with 150 mg dosage (Cohen's d = -6.92, 95% CI: -10.38, -3.47, p &lt; 0.0001). The response rate to omalizumab had a likelihood of being higher with 300 mg of intervention compared to placebo (OR = 8.65, 95% CI = 4.42, 16.93, p &lt; 0.0001). Well-rounded urticarial symptom resolution was observed with 150 mg and 300 mg dosages of omalizumab. Improvement of UAS7 was more comparable with 150 mg dosage, whereas the chance of response to treatment was higher with 300 mg dosage. Our findings support omalizumab as an effective intervention for adult and pediatric populations that are resistant to many therapies, including high-dose H1-antihistamines.

Real-world safety and effectiveness of omalizumab in Japanese patients with chronic spontaneous urticaria: A post-marketing surveillance study

BackgroundThe safety and efficacy of omalizumab in chronic spontaneous urticaria (CSU) patients has been established, but real-world long-term data remain scarce, especially in Japan. Methods52-week, open-label, single-arm, observational study evaluated the safety and effectiveness of first-time omalizumab in Japanese CSU patients responding inadequately to conventional therapies. ResultsOverall, 235 of 280 patients completed the study. Most patients were aged ≥ 18 and < 65 years; adolescents (≥ 12 and ≤ 18 years) accounted for 9.6% of the total population. The mean ± standard deviation (SD) duration of CSU at baseline was 1.6 ± 3.1 years; 46.1% of patients had had CSU for < 6 months. At baseline, the mean ± SD of Urticaria Control Test (UCT) score, Weekly Urticaria Activity Score (UAS7), and Dermatology Life Quality Index (DLQI) were 5.1 ± 3.2, 25.2 ± 11.9, and 8.4 ± 5.9, respectively. The mean ± SD duration of the observation period was 330.3 ± 86.2 days. Relapse was reported in 65 patients, 51, 9, and 5 of whom required retreatment with omalizumab 1, 2, and ≥ 3 times, respectively. The incidence of adverse events (AEs), serious AEs, and adverse drug reactions (ADRs) was reported in 11.8%, 1.4%, and 3.9% of patients, respectively. The most common AEs were urticaria (1.8%) and eczema (1.1%). No adolescents experienced ADRs. A cumulative of 92.8% of patients responded in the Physician's Global Impression of Change, with 81.3%, 75.0%, and 95.1% of patients achieving UCT ≥ 12, UAS7 ≤ 6, and DLQI ≤ 5 up to Week 52, respectively. ConclusionsThis study supports the safety and effectiveness of omalizumab in CSU patients who responded inadequately to conventional therapies in real-world clinical practice in Japan.

Incidence and clinical course of COVID-19 in patients using omalizumab for chronic spontaneous urticaria and/or severe allergic asthma and using mepolizumab for severe eosinophilic asthma: A single center real life experience.

To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents. A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease. Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%). The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

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.

Successful combined treatment with omalizumab and tocilizumab in a case of chronic spontaneous urticaria and rheumatoid arthritis: A case report and literature review

Omalizumab is a recombinant humanized monoclonal anti-IgE antibody used to treat uncontrolled chronic spontaneous urticaria (CSU). Sometimes patients with CSU also have other autoimmune conditions. Recent studies have demonstrated the safety and efficacy of a combination treatment with omalizumab and other biologics. Here, we report the first successful treatment with omalizumab for CSU and tocilizumab for rheumatoid arthritis. Since omalizumab is unlikely to cause severe immunosuppression, it may be a treatment option for CSU, even in patients treated with other biologics.

New markers to predict the response to omalizumab in chronic spontaneous urticaria

Omalizumab has high treatment efficacy in patients with chronic spontaneous urticaria (CSU) who do not respond to high doses of antihistamines. Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were described as novel inflammatory and prognostic biomarkers. The present study aimed to evaluate the effectiveness of SII and SIRI in patients with CSU who receive omalizumab therapy. A total of 124 patients with severe urticaria who had an urticaria activity score over 7 days (UAS-7) ≥28 were included in the study. UAS-7, C-reactive protein (CRP), SII, and SIRI values ​​were recorded before and after omalizumab treatment. Patients with UAS-7 ≤6 at week 12 and/or week 24 of omalizumab treatment were considered responders. Three months after omalizumab treatment, significant decreases were observed in SII, SIRI, CRP, and UAS-7 compared to pre-treatment values ​​(p= 0.003, p< 0.001, p=0.006, and p< 0.001, respectively). At the third and sixth months of treatment, baseline SII and SIRI levels of the omalizumab responder group were significantly higher than the non-responder group (p< 0.001). However, there was no difference in baseline CRP and UAS-7 levels between responders and non-responders (p˃0.05). After adjusting for confounding factors, only pre-treatment SII (OR: 1.002, 95% CI: 1.000-1.004, p=0.036) and SIRI (OR: 4.334, 95% CI: 1.751-10.726, p=0.002) values were independently associated with response to omalizumab at 3 months in multivariate regression analysis. SII and SIRI could be effectively used to predict the response to omalizumab therapy. More comprehensive studies are needed to validate and elaborate on this relationship.