Insights into treatment options for Chronic Spontaneous Urticaria

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Insights into treatment options for
Chronic Spontaneous Urticaria

Dr. Afzal Lodhi,
MBBS, D. Derm, M.Sc. Dermatology

Chronic Spontaneous Urticaria (CSU) is defined as the spontaneous daily, or almost daily, occurrence of itchy hives (wheals), angioedema or both, lasting for 6 weeks or more, with no apparent external trigger. CSU presents a major burden of disease for patients and society with a significantly diminished QoL.

The aim of therapy for CSU is quick and complete symptom control.According to the International EAACI/GA2LEN/EDF/WAO guidelines for the management of CSU, updated in 2013 and published in 2014, second generation H1 antihistamines are recommended first-line treatment for CSU. However, standard therapy with licensed doses of H1-antihistamines is often ineffective; up to 50% of patients have an inadequate response to approved doses of H1-antihistamines. Guidelines recommend an up to 4-fold dose increase in H1-antihistamine second-line, in patients with an inadequate response to H1-antihistamines at licensed doses. This results in a higher degree of efficacy in some, but not all, patients, with up to one third of patients remaining unresponsive.

Treatment options for patients refractory to second generation H1-antihistamines, even at higher doses, are limited. Guidelines recommend third-line addition of either omalizumab, cyclosporin A or montelukast to existing H1-antihistamine treatment. Omalizumab 300 mg is approved in the EU/the US for the treatment of CSU/CIU in adult and adolescent (12 years and above) patients with inadequate response to H1-antihistamine treatment/who remain symptomatic despite H1-antihistamine treatment. Other, unlicensed, treatments are also recommended by guidelines as add-on therapy to second generation H1-antihistamines in refractory CSU. The level of evidence for the efficacy of montelukast in urticaria is low. Efficacy of ciclosporinA in combination with a second-generation H1-antihistamine has been demonstrated in clinical trials, but it is associated with a high incidence of adverse effects.

Omalizumab is a humanized monoclonal IgG antibody against IgE. Omalizumab which inhibits binding of IgE to FcɛRI on the surface of mast cells and basophils, and downregulates, cell surface IgE receptors preventing IgE-mediated histamine release.In Phase III studies, omalizumab 300 mg consistently provided significant improvements in the symptoms of CSU compared with placebo such as:-

  • Significantly reducing weekly ISS by 62–71% from baseline to Week 12, with itch relief being rapid and sustained throughout the treatment period.
  • Significantly reducing DLQI at 12 weeks in ASTERIA I (-10.3 vs -6.1), ASTERIA II (-10.2 vs -6.1) and GLACIAL (-9.7 vs -5.1), corresponding to a 74%, 78% and 73% reduction vs baseline.
  • Significantly reducing weekly hives score at 12 weeks in ASTERIA I (-11.4 vs -4.4), ASTERIA II (-12.0 vs -5.2) and GLACIAL (-10.5 vs -4.5), corresponding to a 67%, 74% and 62% reduction vs baseline.
  • Significantly increasing angioedema-free days over weeks 4–12.
  • Increasing the proportion of patients with an absence of itch or hives (UAS7=0) at 12 weeks [36% (ASTERIA I), 44% (ASTERIA II) and 34% (GLACIAL)].
  • Increasing the proportion of patients with ‘well-controlled disease’ (UAS7≤6) at 12 weeks [52% (ASTERIA I) 66% (ASTERIA II) and 52% (GLACIAL)].
  • In Phase III studies, omalizumab 300 mg was well tolerated in over 700 patients with refractory CSU, with no new safety issues or concerns compared with the known safety profile of omalizumab for the treatment of moderate-to-severe allergic asthma.

Omalizumab is administered by subcutaneous injection and is supplied as a lyophilised formulation for reconstitution. The approved dose is 300 mg (2 x 150 mg) every 4 weeks. Patients should be observed following administration of omalizumab. Prescribers should periodically reassess the need for continued therapy; clinical trial experience of treatment beyond 6 months in this indication is limited.

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