Stepping down of treatment in Chronic Spontaneous Urticaria: A retrospective study comparing tapering vs abrupt discontinuation of antihistamines in patients having well-controlled disease

1. Introduction

Chronic spontaneous urticaria (CSU) is a self-limiting common dermatosis characterized by the presence of itchy wheals, angioedema, or both for 6 weeks or more without any definite cause [1]. The treatment armamentarium of CSU includes second-generation antihistamines (sgAH), omalizumab, and cyclosporine for diseases nonresponsive to sgAH. The International Guidelines recommend an “as much as needed and as little as possible” approach, stepping up and down the therapy on the basis of patient response assessed by various outcome measures [2]. Urticaria control test (UCT), a simple 4-item questionnaire, is a widely used retrospective and simple patient-reported outcome measure for CSU [3]. A UCT score of 16 is considered as complete control, a score of 12–15 is considered as good control, whereas <12 is poor control. Once complete disease control is achieved for more than 3 months (UCT = 16), it is advised to either discontinue or step down the dosage of antihistamine following an appropriate protocol. If symptoms resurface after discontinuation/reduction, patients should resume the last dosage on which they were controlled before attempting reduction again [4]. However, there are no formed recommendations regarding discontinuation of treatment in CSU after disease control is achieved. Stepping-down treatment in CSU (sDown-CSU) study was an international multicenter, cross-sectional, survey/questionnaire-based study that assessed stepping-down approaches for antihistamines in CSU treatment from a global expert perspective [5]. As per our departmental protocol, well-controlled CSU patients on higher than standard dose of sgAHs (eg. levocetirizine 20 mg) are tapered by a reduction of one-fourth dose every month till the standard dose (eg. levocetirizine 5 mg) is reached and the patient is symptom-free for 3 months on the standard dosage. After this, we follow 2 regimens, tapering or abrupt discontinuation, depending upon patient preference. The present study was an attempt to compare patient outcomes using these 2 approaches for discontinuation of standard dose antihistamine treatment in CSU, tapering of antihistamines, or abrupt discontinuation.

2. Materials and methods

This was a retrospective study wherein data were collected for patients who were asymptomatic for 3 months on standard treatment doses of sgAHs (for eg, levocetirizine 5 mg) and had follow-up data for UCT available for at least 3 months after the discontinuation regimen started. Patients with chronic inducible urticaria, CSU with chronic inducible urticaria, and those receiving omalizumab or cyclosporine were excluded from the study.

Thirty patients with CSU were identified after retrospectively assessing records between January 2023 and December 2023 from the urticaria clinic of a tertiary care hospital. Clinico-demographic parameters, including baseline disease control and investigations, were noted. Ours being a referral center, all recruited patients had previously required up-dosing of sgAHs before achieving control at the standard dosage. Identified patients were segregated into 2 groups: tapering (group 1) or abrupt discontinuation (group 2). In group 1 (n = 15), a single sgAH tablet had been tapered alternate day for 1 month, then weekly 2 times/week (Wednesday and Saturday) for the second month and once weekly (Wednesday) for the 3rd month. In group 2 (n = 15), the ongoing antihistamine treatment had been abruptly stopped once the patient was asymptomatic during the last 3 months on a standard dose of sgAHs as assessed by UCT (UCT = 16). Any relapse was treated again with the daily recommended dose of sgAHs for the next 3 months. The data were analyzed in SPSS version 29.0 software. All qualitative variables were assessed by chi-square test. For quantitative parameters, paired t test was used. P value <0.05 was considered significant at all places based on a confidence interval of 95%.

2.1 Demographic parameters and pretreatment data

The mean (SD) age of patients in both groups was comparable (42.0 [17.8] years in group 1 vs 32.1 [13.8] years in group 2) (P = 0.101). There was female predominance (M:F ratio 1:2 in group 1 vs 1:1.25 in group 2). The mean (SD) total duration of illness (TDI) (months) was comparable between 2 groups, 29.2 (22.0) in group 1 vs 44.4 (61) in group 2 (P = 0.380). Basic laboratory parameters like mean (SD) serum immunoglobulin E (IgE-UI/mL), D-dimer (ng/mL), C reactive protein (CRP) (mg/dL), and vitamin D (ng/mL) were comparable between 2 groups. Bilastine was the most commonly administered sgAH, in 11/15(73.3%) patients of group 1 vs 10/15 (66.7%) patients of group 2 (P = 0.461) followed by levocetirizine in the remaining patients.

2.2 Urticaria control test

The disease control assessed by mean (SD) UCT at baseline during treatment initiation reviewed from records was 10.6 (3.5) in group 1 vs 10.6 (2.8) in group 2 (P = 0.95). At 1-month postrelease from treatment, the mean (SD) of UCT₁ was 15.2 (1.14) in group 1 vs 14.0 (1.33) in group 2 (P = 0.019). At 2 months postrelease from treatment, the mean (SD) of UCT₂ was higher in group 1 (15.8 [0.5]) than in group 2 (14.8 [1.08]) (P = 0.002). However, at 3 months, the difference in mean (SD) of UCT₃ between group 1 (15.9 [0.25]) and group 2 (15.6 [0.72]) was deemed insignificant (P = 0.196).

2.3 Number of patients released from treatment at 3 months

At the end of 3 months, the patients released from treatment included 14/15 in group 1 vs 11/15 in group 2 (P = 0.330), the outcome being comparable. One patient in group 1 and 4 patients in group 2 had a relapse and restarted on standard-dose sgAHs. On detailed assessment, they were found to have a lower baseline disease control assessed by UCT (8.2 vs 11.1), lower serum IgE (81 U vs 472 U) (P = 0.005), and higher mean CRP (mg/dL) levels (6.9 vs 3.3) compared to patients released from treatment.

3. Discussion

Stepping-down therapy in CSU is important for a multitude of reasons, such as costs of therapy, safety concerns due to therapy, planning pregnancy, onset of other diseases, various comorbidities and drug interactions, and to check if spontaneous remission has occurred or not [5, 6]. Most therapies for CSU are nondisease modifying and only prolong disease-free survival; antihistamines are inverse-agonists responsible for their long-lasting action. Literature regarding detailed protocol on stepping-down of therapy is not robust, with only expert-based consensus available. Most of the urticaria guidelines provide insufficient guidance, with 72% lacking detailed information on when and how to discontinue [4]. Two approaches have been suggested by authors, tapering of antihistamines or abruptly stopping antihistamines (Fig. 1A). Our study showed that for the initial 2 months, tapering of antihistamines led to better control with higher UCT during the first and second months of follow-up. However, from the third month both the groups were comparable in terms of urticaria control with similar mean UCT (Fig. 1B). The authors advocate a second approach for resource-poor settings to decrease the economic burden, while the first approach is useful in patients with poor baseline urticaria control. Relapses were common in patients with poor baseline disease control, lower serum IgE levels, and higher CRP levels. No other clinical or laboratory parameters were found to affect the stepping-down approach in CSU patients. However, as of now, no head-to-head trials exist comparing these stepping-down approaches apart from ours. Therefore, without any biomarkers to identify spontaneous remission in CSU, stopping of ongoing sgAHs can be done by any of the above approaches. To conclude, this article exemplifies probable methods of ongoing treatment in CSU, in the absence of any recommended guidelines, the methods we chose can be used to stop antihistamines and in those who have relapse should be treated as fresh patients restarting sgAHs at the last controlled dose.

Figure 1.

(A) Stepping-down approaches proposed for patients of CSU. Study was done in patients who were uniformly on standard dose of sgAHs. Approach 1- tapering of antihistamines, Approach 2- abrupt discontinuation of antihistamines. (B) Comparison of UCT at 1, 2, and 3 months of follow-up in 2 groups (orange panel, group 1—tapering of antihistamines) (blue panel, group 2—antihistamines abruptly stopped). CSU, chronic spontaneous urticarial; sgAH, second-generation antihistamines; UCT, urticaria control test.

3.1 Limitations

Retrospective design and short follow-up. We could not find a correlation between baseline up-dosage of antihistamine and the response to discontinuation; as all were receiving up-dosages.

Conflicts of interest

The authors have no financial conflicts of interest.

Author contributions

Kumaran and Parsad were involved in concept, design, and manuscript supervision. Singh and Bishnoi were involved in manuscript preparation and editing. All authors approved the final version of the manuscript.