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A missense mutation of the plasminogen gene in hereditary angioedema with normal C1 inhibitor in Japan
Author(s) -
Yakushiji Hiromasa,
Hashimura Chinami,
Fukuoka Kazuhito,
Kaji Arito,
Miyahara Hisaaki,
Kaname Shinya,
Horiuchi Takahiko
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13550
Subject(s) - hereditary angioedema , missense mutation , exon , proband , medicine , genetics , c1 inhibitor , angioedema , compound heterozygosity , family history , genetic counseling , gene mutation , mutation , gene , dermatology , biology
more toxic drugs in case of relapse. The study was approved by the Internal Review Board of the Clinic. The baseline features of the study patients along with the clinical response to the treatment are shown in Table 1. Seven of 14 patients (50%) showed an ongoing complete control of the disease (UAS7 < 6) despite halving the monthly dose of omalizumab. In the remaining seven patients, the dose reduction was associated with a worsening of the disease (UAS7 score between 7 and 21), although in no case, it returned to the baseline severity. The partial loss of response to the drug did not depend on disease duration, the presence of thyroid autoimmunity, or baseline ESR, CRP, or D‐dimer, whereas it was associated with the baseline severity of the disease (P < 0.05). Also, a history of angioedema was much more frequent among those who worsened following the reduction in omalizumab dosage (6/7, 86%) than in patients who maintained the control of the disease (2/7; 29%), but due to the small number of patients, the difference did not reach the statistical significance. Although studies on larger number of patients are needed to confirm these observations and despite the limitation of being nonrandomized, the present real‐life study suggests that it is possible to halve the costs of omalizumab maintenance treatment in about one half of patients with severe CSU showing a prompt response to the drug at the dose of 300 mg/mo without any loss of clinical efficacy. Patients who worsen with a reduced dosage of omalizumab are in general those showing a more severe diseases at baseline as well as those with a history of angioedema associated with the wheals. This is in keeping with previous observations that in patients with angioedema, only the dosage of 300 mg/month seems to be effective 2 Whether the reduction in omalizumab dosage as a maintenance therapy will work also in patients showing a delayed response to the drug remains to be established. In conclusion, this study confirms previous observations in a very small number of patients 10 that a maintenance monthly dose of 150 mg of omalizumab may be sufficient to guarantee an ongoing control of the disease in a large proportion of patients with CSU showing an early response to the drug.