10.5826/dpc.1204a148
Introduction: Omalizumab has been recently registered as a third-line therapy for chronic spontaneous urticaria.
Objectives: In this study, we aimed to provide real life data by reporting our experience with omalizumab in the treatment of chronic spontaneous urticaria.
Methods: A retrospective data analysis was conducted on 40 patients affected by chronic spontaneous urticaria and treated with omalizumab at the Dermatology Unit of University of Padua, Italy.Demographic, anthropometric, and clinical data have been collected.
Results: Overall, the majority of patients (23 patients, 57.5%) achieved complete recovery by taking omalizumab and 17.5% (7 patients) had a partial response. The majority of patients who did not have a response to omalizumab had a BMI&gt; 25 kg/m2.
Conclusions: Our study suggests that omalizumab is a safe and effective treatment for chronic spontaneous urticaria. We identified BMI as a critical biological factor that significantly impacts the outcomes of omalizumab treatment. Our findings also suggest a potential use of BMI as a predictive biomarker for omalizumab treatment. An updosing of omalizumab may be proposed in patients with high BMI to achieve a better control of the disease.
text/xml
2160-9381
2053
en
Mauro Alaibac
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
chronic spontaneous urticaria
Omalizumab for the treatment of chronic spontaneous urticaria: association between body mass index and outcome
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-10-31
2021-09-19
2022-10-31
2022-11-29
e2022148
Dermatol Pract Concept
Introduction: Omalizumab has been recently registered as a third-line therapy for chronic spontaneous urticaria.
Objectives: In this study, we aimed to provide real life data by reporting our experience with omalizumab in the treatment of chronic spontaneous urticaria.
Methods: A retrospective data analysis was conducted on 40 patients affected by chronic spontaneous urticaria and treated with omalizumab at the Dermatology Unit of University of Padua, Italy.Demographic, anthropometric, and clinical data have been collected.
Results: Overall, the majority of patients (23 patients, 57.5%) achieved complete recovery by taking omalizumab and 17.5% (7 patients) had a partial response. The majority of patients who did not have a response to omalizumab had a BMI&gt; 25 kg/m2.
Conclusions: Our study suggests that omalizumab is a safe and effective treatment for chronic spontaneous urticaria. We identified BMI as a critical biological factor that significantly impacts the outcomes of omalizumab treatment. Our findings also suggest a potential use of BMI as a predictive biomarker for omalizumab treatment. An updosing of omalizumab may be proposed in patients with high BMI to achieve a better control of the disease.
Mauro Alaibac
2022/10/31
10.5826/dpc.1204a148
e2022148
Unit of Dermatology, Department of Medicine (DIMED), University of Padova, Padova, Italy
2160-9381
chronic spontaneous urticaria
en
e2022148
Omalizumab for the treatment of chronic spontaneous urticaria: association between body mass index and outcome
https://dpcj.org/index.php/dpc/article/download/2053/1768
     Omalizumab for the Treatment of Chronic
  Spontaneous Urticaria: Association Between Body
            Mass Index and Outcome
                 Irene Russo1,2, Sara Cazzolla1, Francesca Pampaloni1, Mauro Alaibac1


1 Unit of Dermatology, Department of Medicine (DIMED), University of Padova, Padua, Italy
2 Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV)- IRCCS, Padua, Italy



Key words: omalizumab, chronic spontaneous urticaria, BMI
Citation: Russo I, Cazzolla S, Pampaloni F, Alaibac M. Omalizumab for the treatment of chronic spontaneous urticaria: association
between body mass index and outcome. Dermatol Pract Concept. 2022;12(4):e2022148. DOI: https://doi.org/10.5826/dpc.1204a148
Accepted: January 21, 2022; Published: October 2022
Copyright: ©2022 Russo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Francesca Pampaloni, Unit of Dermatology, Department of Medicine (DIMED), University of Padova, via Gallucci
4, 35128 Padua, Italy. Phone 00390498212901 E-mail: francesca.pampaloni@gmail.com




  ABSTRACT             Introduction: Omalizumab has been recently registered as a third-line therapy for chronic sponta-
                       neous urticaria.
                       Objectives: In this study, we aimed to provide real life data by reporting our experience with omali-
                       zumab in the treatment of chronic spontaneous urticaria.
                       Methods: A retrospective data analysis was conducted on 40 patients affected by chronic spontaneous
                       urticaria and treated with omalizumab at the Dermatology Unit of Padova University Hospital. Demo-
                       graphic, anthropometric, and clinical data have been collected.
                       Results: Overall, the majority of patients (23 patients, 57.5%) achieved complete recovery by taking
                       omalizumab and 17.5% (7 patients) had a partial response. The majority of patients who did not have
                       a response to omalizumab had a body mass index (BMI) > 25 kg/m2.
                       Conclusions: Our study suggests that omalizumab is a safe and effective treatment for chronic spon-
                       taneous urticaria. We identified BMI as a critical biological factor that significantly impacts the out-
                       comes of omalizumab treatment. Our findings also suggest a potential use of BMI as a predictive
                       biomarker for omalizumab treatment. An up-dosing of omalizumab may be proposed in patients with
                       high BMI to achieve a better control of the disease.




Original Article | Dermatol Pract Concept. 2022;12(4):e2022148                                                                      1
Introduction                                                      a month, follow-up visits were scheduled together with the
                                                                  omalizumab infusions. The following data were collected:
Chronic spontaneous urticaria (CSU) is a common disease,          birth date, sex, height, weight, date of urticaria diagnosis,
however, epidemiological data currently available on CSU          severity of the disease, previous urticaria therapies, co-
prevalence ranging from 0.02% to 1% in different ­studies         morbidities, and concomitant medications. The body mass
[1,2]. It is clinically characterized by the recurrent appear-    index (BMI) value was calculated (in kg/m2) to classify pa-
ance of itch, wheals and/or angioedema for more than              tients as underweight (BMI < 18.4 kg/m2), normal weight
6 weeks in absence of a known trigger [3]. It is often a self-­   (18.5 kg/m2≤ BMI ≤ 24.9 kg/m2), overweight (25 kg/m2≤
limiting disease lasting no more than 2-5 years; however in       BMI ≤ 29.9 kg/m2) and obese (BMI ≥ 30 kg/m2). The date of
20% of patients lasts for more than 5 years. Many factors         the first omalizumab administration, the number of therapy
may play a role in the pathogenesis of chronic idiopathic         cycles and the date of the last infusion were recorded as well
urticaria, including infections, diet, drugs, emotional fac-      as any adverse events during or after omalizumab admin-
tors, and stress [1,4]. Chronic spontaneous urticaria highly      istration. The outcome of the treatment with omalizumab
impacts quality of life of patients affected. Pruritus causes     was evaluated based on the patient’s report, any objective
variable discomfort, as well as cutaneous wheals which may        improvement or worsening, and reduction of UAS7. UAS7=0
harm individual physical appearance and social life. The          was considered as complete response, while a 90% reduc-
first line therapy for CSU consists in the use of non-sedating    tion in UAS7 was considered as a partial response. Benefit
H1-antihistamines. If the response is inadequate after two        achieved after a single course of omalizumab was considered
weeks of treatment, increasing the antihistamine dosage up        a partial response.
to four-fold is recommended as second-line therapy [2,4].
Omalizumab, a humanized anti-IgE monoclonal antibody,
that was primarily approved for the treatment of moderate/
                                                                  Results
severe asthma has been recently registered for CSU treatment      The study included 40 patients with the following demo-
as a third-line therapy [5-8].                                    graphic characteristics: 30 females (75%) and 10 males
                                                                  (25%), with a mean age of 49 years (range: 21- 81 years).
Objectives                                                        The minimum BMI detected was 17.8 kg/m2, while the max-
                                                                  imum was 34 kg/m2, with an average value of 24.1 kg/m2.
In this study, we aimed to provide real life data by reporting    The patients were divided in underweight, normal weight,
our experience with omalizumab in the treatment of CSU.           overweight and obese (Table 1). The date of urticaria diag-
                                                                  nosis was between 1994 and 2019. The mean age of patients
                                                                  at the time of the diagnosis was 45 years. All patients were
Methods
                                                                  affected by severe disease with UAS > 4 and UAS7 > 30
A retrospective data analysis was conducted on 40 patients        ­before starting treatment with omalizumab.
affected by CSU and treated with omalizumab between 2016             Medications used before omalizumab for the treatment of
and 2019 at the Dermatology Unit of Padova University             CSU included three main classes of drugs: antihistamines (85%
Hospital.                                                         of patients, mainly desloratadine), glucocorticoids (62.5%
    All patients provided written informed consent. The pa-       of patients, mostly prednisone) and immunosuppressants
tients included were aged over than 18 years with at least        (27.5% of patients, primarily cyclosporine). F
                                                                                                               ­urthermore,
6 months history of chronic idiopathic urticaria. The severity    27.5% of patients followed a histamine-free diet, 10% of
of the urticaria was assessed thanks to the Urticaria Activity    cases received a supplementation with nicotinamide, while
Score (UAS) and established both daily and weekly (UAS7),         5% of patients were treated with UVB phototherapy. The
based on the presence of wheals and itching.                      majority of patients (80%) presented comorbidities includ-
    All patients received a 300 mg subcutaneous injection         ing allergic rhinitis (20%), hypothyroidism (20%), nickel al-
of omalizumab every 4 weeks for at least 6 months. Once           lergy (15%), grasses allergy (12.5%) and atopic dermatitis



   Table 1. Classification of patients based on the BMI value according to the WHO: underweight
(<18.5 kg/m2), normal weight (18.5- 24.9 kg/m2), overweight (25- 29.9 kg/m2) and obese (>30 kg/m2)
         Patient                 Underweight           Normal Weight                Overweight                     Obese
     Female, N (%)                 2 (5%)                 17 (42,5%)                 7 (17,5%)                    4 (10%)
      Male, N (%)                     0                    6 (15%)                      4 (10%)                       0



2                                                                      Original Article | Dermatol Pract Concept. 2022;12(4):e2022148
(12.5%) were detected. Simultaneously to the omalizumab                patients who did not have a response to omalizumab had a
therapy, many patients have taken various therapies for both           BMI > 25 kg/m2.
CSU and their concurrent diseases including antihistamines                 Binomial logistic regression enables us to determine
(60%), glucocorticoids (55%), levothyroxine (15%). In ad-              which of our independent variables have statistically signif-
dition, 15% of patients continued to follow a histamine-free           icant effect on outcome; considering age, sex and BMI as
diet and 12.5% were taking nicotinamide.                               variables, emerged that BMI has a statistically significant
    Overall, 30 patients (75%) completed the entire course             effect (P = 0.042), and odds ratio < 1 indicates a positive
of omalizumab therapy, while 10 of them (25%) discontin-               predictive value of better response to therapy (Table 2).
ued omalizumab due to acute side effects (discontinuation
at the first dose, in 2 patients), other diseases (2 patients)
                                                                       Conclusions
or ineffectiveness (6 patients). Based on the results obtained,
patients were classified into three categories: no response (10        In our cohort patients were predominantly female (M:F ratio
cases, 25%), partial response (7 patients, 17.5%), complete            was 1:3), according to the literature, which reports a prev-
response (23 patients, 57.5%) (Figure 1). The majority of              alence of CSU two times higher among women than man.
                                                                       It may be explained by the role of autoimmunity in CSU




                                        OUTCOME TO OMALIZUMAB TREATMENT




        60%

        50%

        40%

                                                                                                    57.5%
        30%

        20%
                                 25%
                                                                  17.5%
        10%

         0%
                        NO RESPONSE                    PARTIAL RESPONSE                 COMPLETE RESPONSE

                                    NO RESPONSE          PARTIAL RESPONSE COMPLETE RESPONSE


Figure 1. Outcome of omalizumab treatment. Complete response: UAS7=0; Partial response: 90% reduction of UAS7 values; 25% of
­patients (10 patients) had no response; 17.5% of patients (7 patients) reported partial response, while 57.5% (23 patients) had a complete
 response to omalizumab.



                                           Table 2. Model coefficients – outcome
 Predictor                   Estimatea                  SE                      Z                      P                Odds ratio
 Intercept                    3.8904                 2.5292                  1.538                  0.124                  48.930
 BMI                          -0.2105                0.1037                  -2.029                 0.042                   0.810
 Age                          0.0458                 0.0315                  1.452                  0.147                   1.047
 Sex:
 M–F                          0.8918                 1.0390                  0.858                  0.391                   2.439

BMI = body mass index; F =female; M = male; SE = standard error.
a
 Estimates represent the log odds of “Outcome = yes” versus “Outcome = no”



Original Article | Dermatol Pract Concept. 2022;12(4):e2022148                                                                           3
pathogenesis [3]. Patients aged from 21 to 81 years have been      for patients affected by asthma the recommended dose of
treated, showing omalizumab safety in all age groups, even         omalizumab changes according to the body weight of the
in the elderly patients which may have comorbidities [9].          patient, a fixed dose regimen is recommended for CSU re-
The average value of BMI was 24.1 kg/m2, which belongs to          gardless of the body weight and total IgE levels. In the re-
the category of normal weight but with a tendency to over-         cent years, there have been several studies on updosing of
weight. Although the study population is not large, the distri-    the drug, suggesting that the individualized approach for
bution of BMI categories was overlapping to the percentage         urticaria treatment with omalizumab is useful [16]. Patients
obtained by 2016 ISTAT on the entire Italian population.           with a higher BMI have been found to require higher doses
The most common diseases associated with CSU were hypo-            to control the disease [17]. A step-wise approach starting
thyroidism, hypertension, allergic rhinitis, nickel and grass      from 450 mg and then updosing to 600 mg has been pro-
allergy and atopic dermatitis. Several patients included in        posed if there is no response after 3 months of treatment
our case series were also affected by atopic dermatitis, vit-      in CSU patients [17]. Furthermore intervention on lifestyle
iligo, psoriasis, alopecia, SLE, scleroderma, spondylarthritis     through a combination of dietary changing and physical ac-
and/or diabetes suggesting a potential role of autoimmunity.       tivity should be recommended in patients with high BMI.
    Our patients continued their concomitant treatments                Total IgE serum level do not justify an omalizumab dose
during omalizumab cycles, including antihistamines (60% of         changing however, it is a reliable biomarker predicting re-
patients) and low-dose oral corticosteroids (55% of patients)      sponse to omalizumab in CSU since levels are significantly
intake. In addition, 15% of patients continued to follow a         higher in responder than non-responder patients [18].
histamine-free diet and 12.5% were taking nicotinamide. No             The main limitation of our study is the small number of
pharmacological interactions were observed, confirming lit-        patients included. Furthermore, all patients had a high UAS
erature data [7,10].                                               and some patients continued antihistamines and corticoste-
    Most of patients (57.5%) had a complete response.              roids during omalizumab. We know that these may be con-
Moreover, considering partial responses and first cycle bene-      founding factors that may have influenced the outcome.
fits, 30 out of 40 patients (75%) had at least a partial favor-        In conclusion, in this study we identified BMI as a critical
able response. Given the small number of subjects recruited a      biological factor that significantly impacts the outcomes of
statistical analysis has not been performed, but a significant     omalizumab treatment. Our findings also suggest a poten-
number of patients with a beneficial effect from the use of        tial use of BMI as a predictive biomarker for omalizumab
omalizumab has emerged.                                            treatment. An up-dosing of omalizumab may be proposed
    Concerning the occurrence of adverse reactions to omal-        in patients with high BMI to achieve a better control of the
izumab, only 2 cases out of 40 (5%) were reported. Specif-         disease.
ically, a single case of angioedema and 1 case of respiratory
crisis have been documented, leading to therapy discontinu-        References
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6                                                                     Original Article | Dermatol Pract Concept. 2022;12(4):e2022148
