Studies investigating omalizumab in allergic bronchopulmonary aspergillosis (ABPA) treatment in patients with cystic fibrosis (CF)
| Author [ref.] | Type of study | Patients n | Sex (M:F) | Age (years) | CF (yes/no) | ABPA (yes/no) | Reason for omalizumab administration | Objectives | Omalizumab dosage | Treatment duration | Follow-up | Results | Benefit (yes/no) |
| van der Ent [20] | Case report | 1 | 0:1 | 12 | Yes | Yes | CSS dependence CSS side-effects ABPA exacerbations | NA | 300 mg every 2 weeks | 6 weeks | No | Symptoms resolution CSS suspension ↑ FEV1 (transient) = total IgE | Yes |
| Nové-Josserand [19] | Case series | 32 | 1:2 | 11–59 | Yes | Yes | CSS dependence or CSS side-effects | BMI, FEV1, FVC, total IgE levels, concomitant treatment for ABPA | 450 mg (150–1200) every 2, 3 or 4 weeks | Median 18 months (3–50) | No | ↓ (50%) or stop (27.5%) in CSS use No change in FEV1, but wide dispersion of values 9% stopped omalizumab after 20–24 months without exacerbations 22% stopped omalizumab because not effective 12.5% mild AEs | Yes |
| Zirbes [21] | Case series | 3 | 3:0 | 12.8–17 | Yes | Yes | CSS dependence ABPA exacerbations CSS side-effects No response to itraconazole | NA | 300–375 mg s.c. every 2 weeks | 8–18 months | No | ↓ exacerbation rate ↓ hospitalisation Oral CSS suspension =/↑ FEV1 (−4–+19%) | Yes |
| Randhawa [22] | Case report | 1 | 1:0 | 14 | Yes | Yes | CSS dependence CSS side-effects (hyperglycaemia) ABPA exacerbations | NA | 375 mg s.c. every 2 weeks | 6 months | 11 months | CSS suspension Radiological resolution of pulmonary infiltrates ↑ FEV1 | Yes |
| Elmallah [23] | Case report | 2 | 2:0 | 12–16 | Yes | Yes | CSS dependence ABPA exacerbations | NA | 450 mg s.c. every 2 or 4 weeks | 12–18 months | No | ↓ symptoms ↓ exacerbation rate ↓ oral CSS use ↑ FEV1 (+22%) ↓ free IgE (−88– −96%) | Yes |
| Wong [24] | Case report | 2 | 2:0 | 14–15 | Yes | Yes | CSS dependence CSS side-effects ABPA exacerbations | NA | 300 mg s.c. every 4 weeks | 24–32 months | No | ↓ and stop oral CSS use ABPA exacerbation when omalizumab administrated every 6 weeks in patient 1 = FEV1 ↓ free IgE | Yes |
| Lehmann [25] | Case series | 6 | 1:2 | 5–33, 15.6 (±7.1) | Yes | Yes | CSS side-effects or standard treatment failure | NA | Dosage individually adapted to body weight and IgE level at the beginning up to 600 mg every 2 weeks | 19.6 months (±19.1); 2 patients had a 2nd treatment course 10 and 25 months after discontinuation | 7–56 months | No ABPA relapses during treatment ABPA relapses after treatment (2 patients) (33%) ↓ or stop CSS use ↑ FEV1 (+2.3%) | Yes |
| Zicari [26] | Case report | 1 | 0:1 | 13 | Yes | Yes | CSS side-effects (IGT) | NA | 300 mg every 2 weeks, calculated on the weight and total IgE level | 12 months | No | ↓ and stop oral CSS use ↓ antibiotic use ↑ FEV1 (+21%) | Yes |
| Delgado Pecellín [27] | Case series | 3 | 1:2 | 14–29 | Yes | Yes | CSS dependence | NA | 300 mg every 4 weeks to 600 mg every 2 weeks | 5–18 months | No | ↓ and stop oral CSS use No exacerbation ↑/= FEV1 | Yes |
| Perisson [28] | Case series | 18 | 7:11 | 17.1±5.2 | Yes | Yes | Treatment-refractory ABPA, CSS dependence and CSS side-effects Nontuberculous mycobacteria infection | Evaluation at T−3, T0, T3, T6, T12 of: FEV1, BMI, AEC, total IgE levels and A. fumigatus-specific antibody levels, side-effects | 489.7 mg (300–600) every 2 weeks | 12 months | No | ↓ exacerbation rate ↓ or stop CSS use (83%) = FEV1 (p=0.6) = total IgE and AEC ↑ BMI (p=0.01) | Yes |
| Ashkenazi [29] | Case series retrospective study | 9 | 2:1 | 23±9 | Yes | Yes | CSS side-effects Contraindication for CSS Failure of antifungal treatment | FEV1 Number of pulmonary exacerbations BMI CSS dosage | 375 mg every 4 weeks | 13.9±8.6 months | No | No significant improvement of any outcome ↓ CSS use (4 patients) (44%) 3 (33%) patients with ↑ levels of IgE at the end of the treatment had better outcomes than the 6 (67%) patients with ↓ IgE post-treatment | No |
| Koutsokera [30] | Retrospective observational study | 27 (11/27 with ABPA, 16/27 with asthma) | 4:5 | 26.9–42.7 | Yes | Yes (11 ABPA, 16 asthma) | Poor control despite 1st line treatment and/or contraindication or important secondary effects to CSS or antifungal treatment Relapse of asthma or ABPA | Δ FEV1 CSS use Days of hospitalisation Intravenous antibiotics Spirometry measures | 150–750 mg every 4 weeks | 12 months | 0.1–9.9 years | ABPA group: = FEV1 ↓ FEV1 decline and variability No significant change CSS dose (p>0.05) but 1/3 of patients ↓ CSS by 50% | Yes |
| Brinkmann [31] | Case report | 1 | 0:1 | 15 | Yes | Yes | CSS dependence CSS side-effects (growth retardation) | NA | 300 mg every 4 weeks | 12 months | No | Initial ↓ oral CSS use CSS dependence 1 ABPA relapse = FEV1 | Doubtful |
| NCT00787917 [32] | Randomised, double-blind, placebo controlled study, phase 4 | 14 | Yes | Yes | Inclusion criteria: CF complicated by ABPA Oral CSS use for ABPA flare Age ≥12 years (except for Italy; ≥18 years) Total serum IgE levels ≥500 IU·mL−1 | Δ need of rescue CSS Δ ABPA exacerbation rate Δ FEV1 Time to CSS suspension Δ% oral CSS dosage Participants responding to omalizumab, as defined by a reduction in oral CSS dose use of ≥50% as compared with baseline | Up to 600 mg daily + Itraconazole | 6 months | 12 months | Aborted due to difficulties in enrolling patients No published data Early termination of the study Participants dropped out of the intervention group: 1 due to AEs; 1 due to lack of efficacy; and 3 due to administrative problems 6 patients had serious AEs versus 1 in the placebo | |||
| Emiralioglu [33] | Case series | 6 | 1:2 | 11–32 | Yes | Yes | No response or adverse effects of CSS treatment | Monthly evaluation for: symptoms, exacerbation, IgE, spirometry, CSS dosage | 300 mg s.c. every 4 weeks; dosage adapted to body weight and IgE level at the beginning of treatment | 6–18 months | No | No pulmonary exacerbations in 4/6 (66.6%) No ABPA exacerbations in 6/6 (100%) ↓ or stop CSS use ↓ total IgE (p=0.028) = FEV1 (+3%, p=0.91) | Yes, especially if early started |
| Lebecque [34] | Case series | 2 | 1:1 | 14 | Yes | Yes | ABPA exacerbation Alternative to CSS treatment | NA | 375 mg every 2 weeks for 4 months then every 4 weeks for 3 months | 11 injections | No | ↓ symptoms ↑ FEV1 Stable up to 20 weeks following treatment withdrawal (FEV1 of 98% and 99% predicted) | Yes |
| Parisi [35] | Case series | 3 | 3:0 | 11–28 | Yes | Yes | No or poor improvement with CSS and antifungal treatment | NA | 375–600 mg every 2 weeks s.c. | 8 weeks | No | ↓ symptoms ↓ total IgE (↓ 60–70%) ↑ FEV1 (+28–50%) | Yes |
| Kanu [37] | Case report | 1 | 0:1 | 13 | Yes | Yes | CSS side-effects (IGT) | NA | 300 mg s.c. every 2 weeks | 11 weeks | No | ↓ symptoms ↑ FEV1 (+36%) | Yes |
| Thomas [38] | Case report | 1 | 1:0 | 11 | Yes | Yes | CSS dependence CSS side-effects (IGT) | NA | 375 mg every 2 weeks s.c. | 16 weeks | No | ↓ symptoms ↓ systemic CSS use ↑ FEV1 BMI improvement 12 months after, patient needed omalizumab again | Yes |
M: male; F: female; CSS: corticosteroids; NA: not applicable; FEV1: forced expiratory volume in 1 s; BMI: body mass index; FVC: forced vital capacity; s.c.: subcutaneous; IGT: impaired glucose tolerance; AEC: absolute eosinophil count; AE: adverse event.