Cyclosporin (CIC) is the third line of treatment for patients with chronic spontaneous urticaria (CSU) due to a failure to respond to the use of sgAH and omalizumab (OMA).  In some cases, it may be possible outside the indications of the guidelines, to combine omalizumab and cyclosporin therapy at low doses. 

Our objective is to characterize these patients in order to define the features of the  clinical phenotype.

We conducted a retrospective study involving 740 CSU patients referred to our center between 2013 and 2023. Anthropometric data were collected, covering comorbidities, pathology phenotype, treatments response, duration, laboratory data for IgE, AbTPO, AbTG and ANA.

During the study period 24/740 patients underwent CIC, of which 50% without benefit then classified as failure, 41.6% still ongoing as monotherapy or as add-on to omalizumab (=4); 1 patient stopped treatment due to side effects and 1 was lost to follow- up. Comparing  the clinical phenotypes, CIC therapy was ongoing only in those with hives or hives and angioedema (=8). The phenotype of the 4 patients on combined therapy remained stable over time for 2; while 2 patients presented the angioedema component appearance besides urticaria over time.

Finally, 4 patients received combined therapy with low-dose cyclosporine 3 mg/kg and OMA. This subgroup was identified by observing a complete clinical response early at the start of CIC after the last dose of OMA in those failing monotherapy , then apparently losing response at 1 month of CIC monotherapy, then fully responding again with combined treatment. Those patients were rechallenged for multiple times by pausing either OMA (every 12 months) or CIC. No side effects were observed.. There were no significant differences when comparing OMA, CIC and CIC plus OMA groups for age, gender, age at onset, duration BMI,  total IgE, TPO/IgE, frequency of classic comorbidities, except for baseline UAS7 higher in CIC and CIC plus OMA than OMA alone (38 vs 32; p=0.041).

Those patients requiring the combination therapy to achieve control do not show features that may help to identify this subgroup, except for a higher baseline UAS7 score. Although with the inherent limitation of a small retrospective study, our data support the efficacy of a combination of OMA with CIC for CSU refractory to third-line therapy until new therapeutic options will be available.