Cyclosporine in chronic idiopathic urticaria: A double-blind, randomized, placebo-controlled trial

doi:10.1016/j.jaad.2006.04.078

Journal of the American Academy of Dermatology

Volume 55, Issue 4, October 2006, Pages 705-709

https://doi.org/10.1016/j.jaad.2006.04.078 Get rights and content

Background

Treatment of severe recalcitrant chronic idiopathic urticaria (CIU) is difficult.

Objective

To assess the efficacy and safety of oral cyclosporin A (CsA) in CIU.

Methods

The response to CsA was evaluated in 99 CIU patients with a double-blind, randomized, three-armed study: 16-week CsA, 8-week CsA +8-week placebo, and 16-week placebo. All patients received cetirizine throughout the study period and were followed-up after 8 weeks.

Results

Fewer therapeutic failures occurred with 16-week CsA (n = 3) than with placebo (n = 11) and 8-week CsA (n = 8). After 8 and 16 weeks, symptom scores significantly improved in both CsA groups over with placebo. Two patients discontinued because of hypertension.

Limitations

During the study period, CsA was not administered at a constant dose; from day 28 the daily dose was 3 mg/kg, which is likely to be less effective and better tolerated than higher dosages.

Conclusion

CsA in addition to background therapy with cetirizine may be useful in the treatment of CIU.

Section snippets

Methods

The study population, recruited in 18 Italian outpatient clinics, consisted of adult patients suffering from severe relapsing CIU, with persistence of symptoms (total severity score ≥8) despite treatment with cetirizine. Severity score was assessed by means of the scale reported by Breneman et al.¹⁰ Exclusion criteria included other concomitant forms of urticaria, any contraindications to cetirizine and CsA, and relevant systemic disorders.

After a 1-week run-in period with cetirizine, 10 mg/d,

Results

A total of 99 subjects were randomized and received treatment and at least one efficacy evaluation. Baseline characteristics and exposure to study drug are shown in Table I.

Thirty-eight patients did not complete the study: 16-week CsA (n = 8), 8-week CsA (n = 13), and placebo (n = 17). A higher proportion of therapeutic failures both in the placebo group and in the 8-week CsA group during the placebo intake was observed when compared with the 16-week CsA group (Fig 1).

Cumulative efficacy

Discussion

Our results show that oral CsA treatment (5 mg/kg/d progressively reduced to 3 mg/kg/d), in addition to background therapy with cetirizine, is significantly more effective than placebo and cetirizine in reducing the severity of CIU after 8 weeks. There was also a higher incidence of withdrawals because of inefficacy in the placebo group than in the two CsA groups. The amelioration of severity score over placebo still persisted at week 16.

These findings are consistent with the results of another

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Cited by (178)

Letter to the editor regarding “Comparing four immunosuppressive agents for chronic spontaneous urticaria – A network meta-analysis”
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Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents.
The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU.
PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects.
This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples.
Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.
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Urticaria is a heterogeneous inflammatory disorder that can be acute or chronic and is defined by the appearance of wheals, angioedema, or both. Very recently, the newest update and revision of the international European Academy of Allergy and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/Asia Pacific Association of Allergy Asthma Clinical Immunology guideline for the definition, classification, diagnosis, and management of urticaria was published. It aims to help primary care physicians and specialists in the management of their patients with urticaria. The guideline applied the Grading of Recommendations Assessment Development and Evaluations approach to developing consensus recommendations. These recommendations were then discussed in a Delphi conference that included more than 250 specialists in the field, and they are endorsed by more than 50 international societies. Here, we highlight changes from previous versions of the international urticaria guideline and their impact on clinical practice.
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Supported by Novartis Farma SpA, Origgio, Varese, Italy.

Disclosure: Dr Colombo and Ms Peruzzi are full-time employees of Novartis Farma SpA. The other authors declare no conflicts of interest.

Presented previously as an abstract at the II International Symposium on Urticaria, November 23 and 24, 2001, Rome, Italy and at the 60th Annual Meeting of the American Academy of Dermatology, February 22-27, 2002, New Orleans, La; also presented as a poster and abstract at the Second 20th World Congress of Dermatology, July 1-5, 2002, Paris, France.

^∗: The complete list of all investigators and their sites is given at the end of the article.

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Brief ReportCyclosporine in chronic idiopathic urticaria: A double-blind, randomized, placebo-controlled trial

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Methods

Results

Discussion

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Ann Allergy Asthma Immunol

Treatment of severe, chronic urticaria with cyclosporin A

Eur J Dermatol

La ciclosporina A nel trattamento dell'orticaria cronica idiopatica severa. Studio clinico su otto casi

Boll Dermatol Allergol Profess

Trattamento dell'orticaria cronica: chetotifene versus cetirizina in schema sequenziale con ciclosporina A

Boll Dermatol Allergol Profess

Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria

Allergy

Brief Report
Cyclosporine in chronic idiopathic urticaria: A double-blind, randomized, placebo-controlled trial