5% 50% 90% 100%

48 Dermatology and Dermatologic Surgery

the use of angiotensin receptor antagonists appeared to have no increased

risk of angioedema. Further analysis is needed to completely rule out an in-
creased risk of angioedema for new users of angiotensin receptor antago-
nists.

The data presented by Johnsen et al provide a reminder that ACE inhibitors

induce angioedema and that the risk persists even after long-term use.1 How-
ever, the use of angiotensin receptor antagonists does not appear to be asso-
ciated with an increased risk of angioedema.
B. H. Thiers, MD
Reference

1. Vleeming W, van Amsterdam JGC, Stricker BHC, et al: ACE inhibitor-induced

angioedema. Incidence, prevention and management. Drug Saf 18:171-188, 1998.

Once-Daily Fexofenadine Treatment for Chronic Idiopathic Urticaria: A

Multicenter, Randomized, Double-blind, Placebo-controlled Study
Kaplan AP, Spector SL, Meeves S, et al (Med Univ of South Carolina, Charles-
ton; Cedars-Sinai Med Ctr, Los Angeles; Sano-Aventis Pharma, Bridge-
water, NJ)
Ann Allergy Asthma Immunol 94:662-669, 2005 12

Background.Chronic idiopathic urticaria (CIU) can have a profound

effect on patients health and quality of life.
Objective.To evaluate the efcacy and safety of once-daily dosing of
fexofenadine hydrochloride, 180 mg, on CIU.
Methods.This randomized, double-blind, parallel-group, placebo-
controlled study consisted of a placebo run-in period followed by a 4-week
treatment period. Patients 12 years and older with active CIU were random-
ized 2:1 to receive once-daily fexofenadine, 180 mg, or placebo. The pri-
mary end points were change from baseline in mean daily number of wheals
(MNW score) and mean daily severity of pruritus during treatment. Second-
ary efcacy measures included modied total symptom scores and MNW
and pruritus severity scores evaluated weekly and instantaneously at trough
drug levels.
Results.Patients administered fexofenadine (n 163) experienced sig-
nicantly greater improvements in MNW and pruritus severity scores com-
pared with the placebo group (n 92) (P < .001 for both). Similarly,
throughout treatment and at each individual week, the mean reductions in
modied total symptom scores were signicantly greater in the fexofenadine
group (P .005 for all comparisons vs placebo). The mean reductions in
instantaneous MNW and pruritus severity scores were greater in patients in
the fexofenadine group than in those who received placebo (MNW score:
P .015; pruritus severity score: P < .001). There were no signicant differ-
ences in the frequency of treatment-emergent adverse events between the 2
treatment groups.
 5% 50% 90% 100%

Chapter 1Urticarial and Eczematous Disorders 49

Conclusions.A once-daily dose of fexofenadine hydrochloride, 180 mg,

offered effective, well-tolerated relief for the management of CIU.

I have found fexofenadine (Allegra) to be effective in the treatment of

chronic urticaria, although rarely as monotherapy. More often, I tell patients to
use it in the morning (because of its nonsedating properties) with the addition
of doxepin or cetirizine at bedtime.
B. H. Thiers, MD

Evidence of a Role of Tumor Necrosis Factor in Refractory Asthma

Berry MA, Hargadon B, Shelley M, et al (Univ Hosp of Leicester Natl Health
Service Trust, England)
N Engl J Med 354:697-708, 2006 13

Background.The development of tumor necrosis factor (TNF-) an-

tagonists has made it feasible to investigate the role of this cytokine in refrac-
tory asthma.
Methods.We measured markers of TNF- activity on peripheral-blood
monocytes in 10 patients with refractory asthma, 10 patients with mild-to-
moderate asthma, and 10 control subjects. We also investigated the effects of
treatment with the soluble TNF- receptor etanercept (25 mg twice weekly)
in the patients with refractory asthma in a placebo-controlled, double-blind,
crossover pilot study.
Results.As compared with patients with mild-to-moderate asthma and
controls, patients with refractory asthma had increased expression of
membrane-bound TNF-, TNF- receptor 1, and TNF-converting en-
zyme by peripheral-blood monocytes. In the clinical trial, as compared with
placebo, 10 weeks of treatment with etanercept was associated with a sig-
nicant increase in the concentration of methacholine required to provoke a
20 percent decrease in the forced expiratory volume in one second (FEV1)
(mean difference in doubling concentration changes between etanercept and
placebo, 3.5; 95 percent condence interval, 0.07 to 7.0; P0.05), an im-
provement in the asthma-related quality-of-life score (by 0.85 point; 95 per-
cent condence interval, 0.16 to 1.54 on a 7-point scale; P0.02), and a
0.32-liter increase in post-bronchodilator FEV1 (95 percent condence inter-
val, 0.08 to 0.55; P0.01).
Conclusions.Patients with refractory asthma have evidence of up-
regulation of the TNF- axis. (ClinicalTrials.gov number, NCT00276029.)