Omalizumab (Xolair) in children with seasonal allergic rhinitis: leukotriene release as a potential in vitro parameter to monitor therapeutic effects.
To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3-17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy.
Kopp
Matthias Volkmar
MV
University Children's Hospital, Freiburg, Germany. matthias.kopp@uniklinkik-freiburg.de
Stenglein
Stefan
S
Kamin
Wolfgang
W
Friedrichs
Frank
F
von Berg
Andrea
A
Zielen
Stefan
S
Hamelmann
Eckard
E
Wahn
Ulrich
U
Kuehr
Joachim
J
D000293:Adolescent; D000485:Allergens / Q000008:administration & dosage*; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D029662:Betula / Q000276:immunology*; D002648:Child; D003131:Combined Modality Therapy; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005858:Germany; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D017998:Leukotriene D4 / Q000378:metabolism; D017999:Leukotriene E4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D000069444:Omalizumab; D006109:Poaceae / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000485:Allergens; D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015289:Leukotrienes; D017997:Leukotriene C4; D000069444:Omalizumab; D017998:Leukotriene D4; D017999:Leukotriene E4