Background
Monoclonal Antibody | Mechanism of action and route of administration |
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Omalizumab
| Human monoclonal antibody IgG1κ, subcutaneous. It binds to free IgE by inhibiting its binding to high- and low-affinity IgE receptors (FcεRI and CD23). This reduces the expression of the aforementioned receptors in mast cells, basophils, and dendritic cells, limiting the type 2 immune response mediated by IgE. It also modulates the production of interferon-alpha (IFN-α) dendritic cells, reducing virus-induced exacerbations. |
Mepolizumab
| Humanized monoclonal antibody IgG1κ, subcutaneous. It inhibits the maturation, activation, proliferation, and recruitment of eosinophils. It binds to a specific epitope of IL-5, preventing its interaction with the IL-5 receptor (IL-5Rα). |
Reslizumab
| Humanized monoclonal antibody IgG4κ, intravenous. It inhibits the maturation, activation, proliferation, and recruitment of eosinophils. It binds to IL-5, preventing its binding to IL-5Rα. It’s in vitro affinity for IL-5 and its ability to suppress proliferation is greater than that of mepolizumab. |
Benralizumab
| Humanized monoclonal antibody IgG1κ, subcutaneous. It binds to the alpha subunit of the receptor (IL-5Rα) avoiding the transduction of eosinophil survival signals. In addition, there is an amplified apoptosis mechanism induced by the activation of the FcyRIIIa (CD16a) receptor, mediated by natural killer cells and macrophages through a process called antibody-dependent cellular cytotoxicity. It reduces eosinophils and basophils. |
Dupilumab
| Human monoclonal antibody IgG4, subcutaneous. It binds to the alpha subunit of the IL-4 receptor (IL-4Rα) shared by IL-4 and IL-13, thereby inhibiting the type 2 immune response. Simultaneous receptor blockade occurs in hematopoietic and nonhematopoietic cells. |
Materials and methods
Search strategy
Selection of studies and data collection
Eligibility criteria
Study selection and data abstraction
Study | Design | Follow-up | Participants | Intervention | Outcomes | Excluded | Variables | Results |
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Brenard et al. 2020 [19]. | Multicenter, open-label, retrospective study (real-life study) | Median follow-up 9 months from diagnosis to start of mepolizumab. Median follow-up after initiation of mepolizumab 9 months (6–12 m) | 12 patients, 2 excluded. Total 10 (5 men, 5 women) | Mepolizumab 100 mg every 4 weeks (6 patients: approved dose for severe asthma; 4 patients: 300 mg every 4 weeks/EGPA and hypereosinophilic syndrome) | - Annual relapse rate - Use of systemic corticosteroids before and after the start of mepolizumab - Lung lesions, evaluated by CT before starting the biological and at the last follow-up while on the biological | -Patients with eosinophilia related to JAK1 inhibitors and PDGFRα- FIP1L1. -Multiorgan involvement (heart, skin) -Infections -Findings secondary to other medications | Peripheral eosinophilia, BAL, lung function, CT, Comorbidities, and exposures Relapse: symptoms (cough, dyspnea) with increased pulmonary eosinophils, radiographic or CT changes in the absence of infection. -All had at least 1 relapse before mepolizumab. | No significant differences between doses of mepolizumab. Annual relapse rate reduction. Decrease in eosinophils at 3 months. 7 of 8 evaluated by CT had complete resolution, after the 6th month of mepolizumab. Two patients were evaluated with radiography at 6 months and no alterations were found. OS dose reduction in 9 patients at the 3rd month. At the 6th month only one patient still took OS, but in low doses due to tolerance of the decline. No patient had secondary events in the study. |
Askin & Morris 2021 [20]. | Retrospective Case Series | Not described | 53 patients, 12 received biological. | Mepolizumab Benralizumab They do not describe doses, nor do they describe treatment allocation | Improvement in radiological, clinical, psychological changes; relapses; decrease or suspension of corticosteroid | Hypereosinophilic syndrome, patients who did not have a BAL study, or a report of eosinophils in BAL < 20% | Not described | All had sustained improvement in radiological and clinical changes, including lung function and psychological field. There were no relapses. OS decreased in all patients. No patient had serious secondary events. |
Tashiro et al. 2022 [21]. | Retrospective Case Series | Patient 1:8 months Patient 2:4 months Patient 3:19 months Patient 4:17 months | 30 patients with the diagnosis, 12 relapses (6 had > 2 relapses), 4 received anti-IL5 biologic | 2 men aged 68 and 74: Mepolizumab 100 mg every 4 weeks. 2 women aged 67 and 37: Benralizumab 30 mg every 4 weeks × 3 doses, then 30 mg every 8 weeks | Relapses, decrease in eosinophils, withdrawal, or reduction of corticosteroid dose | Findings due to drugs, mycoses, parasitic diseases, EGPA, ABPA, and other systemic diseases. | Patients with T0 > 37.5 °C, cough > 2 weeks, pulmonary infiltrates on CT, eosinophilia > 1000, BAL eosinophils > 25%, improvement of changes after initiation of steroids | 1. Patient with type 2 diabetes, without relapses after starting benralizumab. Improvement at 4 weeks in FEV1 and absence of eosinophils. Systemic corticosteroid was withdrawn. 2. Patient without comorbidities, without relapses after starting benralizumab. Absence of eosinophils, there is no complete withdrawal of systemic corticosteroid, but dose reduction continues. 3. Patient with hypertension, hyperlipidemia, and heart failure, without relapses after the start of mepolizumab, at 4 weeks eosinophil reduction. Systemic corticosteroid was withdrawn. 4. Patient with type 2 diabetes mellitus, without relapses after the start of mepolizumab, at 4 weeks eosinophil reduction. Systemic corticosteroid was withdrawn. |
Doses | Number of participants | Duration of follow-up after biological | Age/sex/Comorbidities | Outcomes | Case report reference | ||||||
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Respiratory symptoms | Relapses | Systemic corticosteroid | Radiological findings | Lung function | Quality of life | Adverse events | |||||
30 mg every 4 weeks for 3 doses then every 8 weeks | 1 | 8 months | Male, 16 years old. Cortico dependent evolution, weight gain, muscle weakness | Symptom improvement immediately after onset | No relapses after initiation | OS dose was reduced after 4 months, then stopped | Not described | Improvement after the start a | Improvement after the start a | No adverse events during handling | David, Y. et al. 2021 [22]. |
Single dose, no dose mentioned | 1 | 9 months | Female, 43 years old. Smoker: 10 cigarettes/day. Relapse, refused restarting systemic corticosteroids | Improvement after administration in the first week | None after start | They did not indicate him, only biological | Significant improvement at one month | Not described | Not described | Not described | Izumo et al. 2020 [23]. |
30 mg single dose | 1 | 4 months | Female, 58 years old. Severe asthma, eosinophilic otitis media. Frequent relapses. Did not undergo LBA | Symptom improvement at 2 weeks, asymptomatic at 8 weeks | None after start | Not indicated, the biological was started | Improvement at 2 weeks with complete resolution at 8 weeks | FENO reduction at 2 weeks (102 vs. 82) | Not described | Not described | Isomoto et al. 2020 [24]. |
30 mg every 4 weeks, for 3 doses | 1 | 3 months | Female, 31 years old. Did not undergo LBA. Did not accept treatment with a systemic steroid | Improvement at 2 weeks | None after start | They did not indicate him, only biological | Normalization at 5 weeks | Not described | Not described | Not described | Izhakian et al. 2022 [25]. |
30 mg every 4 weeks for 3 doses, then 30 mg every 8 weeks | 1 | 24 months | Female, 52 years old. Asthma: multiple relapses | Complete improvement with ACT at 2 months | None after initiation of treatment. Sustained clinical and radiological improvement at 6, 9, and 24 months of follow-up | Allows reduction of corticosteroid 2 months after starting treatment | Complete resolution at 7 months (TC) | Normalization 5 months after treatment | Not described | No adverse events during handling | Angeletti et al. 2022 [26]. |
Do not describe | 1 | Not described | Female, 83 years old. Severe asthma, eosinophilic bronchiolitis | Improvement after the start a | None after start a | Tolerated descent and withdrawal a | Resolution after treatment a | Improvement after the start a | Improvement a | No adverse events during handling | Takano et al. 2021 [27]. |
30 mg every 4 weeks for 3 doses, then 30 mg every 8 weeks | 1 | 30 months | Male, 57 years old. Asthma, allergic rhinitis, eczema, anxiety, depression, prostate hypertrophy. Cortico dependence, type 2 diabetes, osteopenia | Improvement after the start. a | None after the start. Continued with management without relapses | Reduction at 3 weeks | Resolution after treatment a | Improvement after treatment a | Not described | Not described | Ricketti & Ricketti 2021 [28]. |
30 mg every 4 weeks | 1 | 12 months | Female, 70 years old. Severe asthma | Improvement a week | None after start | Not indicated. The biological was started | Improvement after a week, with complete resolution at 4 weeks | Improvement at 4 weeks after handling | Not described | No adverse events during handling | Yazawa et al. 2021 [29]. |
Not mentioned | 1 | Not described | Male, 57 years old. Smoker, 20 pack-years. Cortico dependent | Improvement after the start a | Not described | Not described | Not described | Not described | Not described | Not described | Braga et al. 2020 [30]. |
30 mg every 4 weeks | 1 | Not described | Female, 31 years old. Steroid-induced diabetes, Cushing syndrome, oxygen requirement | Improvement within a week (less need for oxygen) | Not described | Not described | Not described | Not described | Not described | Not described | Garcia-Saucedo et al. 2019 [31]. |
Doses | Number of participants | Duration of follow-up after biological | Age/sex/Comorbidities | Outcomes | Case report reference | ||||||
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Respiratory symptoms | Relapses | Systemic corticosteroid | Radiological findings | Lung function | Quality of life | Adverse events | |||||
100 mg every 4 weeks. Benralizumab 30 mg every 4 weeks for 3 doses, then every 8 weeks | 1 | 24 months Not described | Female, 58 years old. Severe asthma | Significant improvement at 4 months with ACT in control range After relapse improvement, keeping ACT in control range | None after start 1 relapse with onset | Tolerated slow decline with suspension at 12 months. Tolerated descent and suspension after relapse | Resolution at 4 months It had no alterations | Improvement at 4 months It had no alterations | Not described Not described | No adverse events during handling No adverse events during handling | Shimizu et al. 2020 [32]. |
100 mg every 4 weeks for 6 months, then Reslizumab 3 mg/kg every 4 weeks | 1 | 14 months | Female, 42 years old. Type 2 diabetes, smoker 28 pack-years, frequent relapses, Cushingoid facies, acne | Improvement at 2 weeks | None after initiation of mepolizumab, 1 relapse with Reslizumab | Dose reduction at 2 weeks, suspension at 2 months | Improvement after the start a | Not described | Not described | Injection site reaction and mild anaphylaxis with mepolizumab at 6 months was discontinued. No events with Reslizumab | Sarkis et al. 2020 [33]. |
100 mg single dose | 1 | Not described | Female, 57 years old. Severe asthma, type I diabetes mellitus required bronchial thermoplasty | Improvement after treatment a | None after start a | Suspended, followed by starting the biological | Resolution after treatment a | Not described | Not described | Not described | Otoshi et al. 2020 [34]. |
100 mg every 4 weeks | 1 | 7 months | Male, 45 years old. Asthma, cortico dependent | Improvement after the start a | None after start | Tolerated descent and withdrawal a | Not described | Not described | Not described | It caused the suspension of the biological, but they do not expand or characterize it | McKillion et al. 2021 [35]. |
Every 4 weeks, no dose mentioned | 1 | 9 months | Female, 38 years old. Major depression and anxiety. Insomnia and weight gain | Improvement after initiation being significant at month 8 | No relapses after initiation | Allows descent and suspension 5 months after initiation | Not described | Not described | Not described | Not described | Cyca et al. 2022 [36]. |
100 mg every 4 weeks | 2 | 15 months 6 months | Case 1: Female, 56 years old. Type 2 Diabetes Mellitus Case 2: Male, 48 years old. Asthma, rhinitis, type 2 diabetes mellitus, depression | Improvement after the start a | None after start | Tolerated descent and withdrawal a | Normalization in X-ray and CT in both cases a | Case 1: FEV1 from 55% pretreatment to 85% posttreatment a Case 2: FEV1 from 60% pretreatment to 72% posttreatment a | Not described | Not described | Eldaabossi et al. 2021 [37]. |
100 m every 4 weeks | 1 | 12 months | Female, 66 years old. Corticodependent asthma, atrial fibrillation, oxygen demanding, received management with Omalizumab without improvement | Improvement after the start, they withdraw oxygen a | None after start a | Tolerated descent and withdrawal a | Not described | Not described | Not described | Not described | Benipal et al. 2021 [38]. |
100 mg every 4 weeks for 14 doses then every 8 weeks 100 mg every 4 weeks for 12 doses then every 8 weeks | 2 | 36 months 24 months | Case 1: Male, 24 years old. Asthma No BAL or biopsy for diagnosis. Case 2: Female, 26 years old. Asthma Corticodependence | Improvement after the start a Improvement after the start a | None after start None after start | Tolerated decline with suspension at 10 months. Tolerated decline with suspension at 10 months | Complete resolution at 14 months, sustained at 36 months. Complete resolution at 12 months, sustained at 24 months | Improvement at 14 months, sustained at 36 months. Improvement at 12 months, sustained for 24 months | Not described Not described | No adverse events during handling No adverse events during handling | Sato et al. 2021 [39]. |
300 mg every 4 weeks | 1 | 18 months | Female, 55 years old. Asthma, atopic dermatitis, rhinitis, anxiety. Corticosteroid intolerance | Improvement after treatment a | None after start a | Allows corticosteroid decrease | Not described | Not described | Not described | No adverse effects r | Kisling et al. 2020 [40]. |
No dose indicated | 1 | Not described | Female, 47 years old. Corticodependent | Improvement after treatment a | None after start a | Tolerated reduction and withdrawal a | Not described | Not described | Not described | Not described | Askin et al. 2020 [41]. |
100 mg every 4 weeks | 1 | 10 months | Female, 59 years old. Asthma HTN, hyperglycemia, osteoporosis | Improvement after 3 months with ACT in adequate control | None after start | Not indicated. The biological was started | Resolution 3 months after starting treatment | Improvement after treatment a | Not described | No adverse events during handling | Ciuffreda et al. 2020 [42]. |
300 mg every 4 weeks | 1 | Not described | Female, 55 years old. Asthma, anxiety, and steroid-related hallucinations | Improvement after the start a | Not described | Tolerated descent a | Not described | Not described | Not described | Not described | Jones et al. 2019 [43]. |
100 mg every 4 weeks | 1 | 12 months | Female, 47 years old. Asthma, rhinitis. 3 relapses (2 in less than 6 weeks | Improvement after the start a | None after start | Tolerated descent and withdrawal a | Not described | Not described | Not described | Not described | McInnis et al. 2019 [44]. |
100 mg every 4 weeks | 2 | 2 months | Case 1: Female, 54 years old. Asthma, rhinitis, chronic rhinitis with nasal polyps, idiopathic thrombocytopenic purpura. Diagnosed in 2012. Two relapses Case 2: Female, 21 years old. Nonallergic asthma, rhinitis, sensorineural hearing loss. Diagnosed in 2015. Three relapses | Significant improvement 8 weeks after starting the biological | None after start | Case 1: Tolerated decline but is maintained by hematological comorbidity. Case 2: Tolerated decrease to 5 mg/alternate days prednisolone | Not described | Case 1: pretreatment FENO > 300 ppb, post treatment 157 ppb Case 2: not described | Not described | Not described | Mendes et al. 2019 [45]. |
Not describe doses. | 1 | 4 months | Female, 60 years old. Severe asthma, eosinophilic bronchiolitis | Improvement after the start a | No relapses after initiation | Not indicated, the biological was started | Improvement a | Improvement a | Not described | Not described | Tomyo & Sugimoto 2019 [46]. |
They do not describe doses. Vedolizumab continued | 1 | 6 months | Female, 49 years old. HBP, ulcerative colitis in management with vedolizumab and nodular prurigo, ex-smoker. Diagnosis by lung biopsy. Corticodependence | Significant improvement 7 days after onset | No relapses after initiation | Allows descent | Significant improvement at 6 months | Not described | Not described | No adverse events during handling | Lawrence et al. 2019 [47]. |
100 mg every 4 weeks | 1 | 13 months | Male, 65 years old. Asthma relapses. | Resolution at 4 weeks | None after the start, continued with management | Not indicated. It was switched to the biological | Resolution 3 months after starting treatment | Not described | Not described | No adverse events during handling | To et al. 2018 [48]. |
Doses | Number of participants | Duration of follow-up after biological | Age/sex/Comorbidities | Outcomes | Case report reference | ||||||
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Respiratory symptoms | Relapses | Systemic corticosteroid | Radiological findings | Lung function | Quality of life | Adverse events | |||||
150 mg every 4 weeks. Mepolizumab 100 mg every 4 weeks | 1 | 12 months 18 months | Female, 48 years old. Asthma, chronic rhinosinusitis without polyps. Diagnosis by biopsy | Partial improvement with Omalizumab. No symptoms after 4 weeks of initiation of mepolizumab | None after start | Reduction of the dose, but allows to suspend it. Allows reduction and suspension 24 months after starting mepolizumab | No improvement during the 12 months with Omalizumab Complete resolution 14 months after the start of mepolizumab | No improvement during the 12 months with Omalizumab Improvement 3 months after starting mepolizumab, normalization at 12 months | Not described | No adverse events during handling | Lin et al. 2019 [49]. |
300 mg every 2 weeks for 9 months. Dose per total IgE level. 225 mg every 2 weeks for 3 months. Dose per total IgE level. Then, 150 every 2 weeks for 2 months | 2 | 33 months 20 months | Case 1: Male, 17 years old. Asthma, sensitization to aeroallergens. Case 2: Male, 19 years old. Asthma, sensitization to aeroallergens | Improvement after the start, being complete at 9 months. Complete improvement at one month | No relapses after initiation No relapses after initiation | Allows descent and suspension 5 months after initiation. Allows descent with suspension one month from the start | Improvement at 5 months Improvement at 5 months | Not described Not described | Not described Not described | No adverse events during handling No adverse events during handling | Shin et al. 2012 [50]. |
300 mg every 2 weeks. Dose per total IgE level 429 IU/mL. Treatment for 18 months. Restart after relapse at the same dose for 24 months | 1 | 69 months | Female, 68 years old. Osteoporosis, aeroallergen sensitization | Improvement after the start. a Relapse 10 months after withdrawal, with improvement a few weeks after initiation. a After stopping it, without relapses at 17 months | 10 months after the withdrawal so it is restarted, without relapses 2 years after the restart | Descent after a few weeks. It requires restart after relapse, tolerating descent and withdrawal. a | Complete normalization at 17 months. After relapse, normalization at 2 years after restart. | Not described | Not described | Not described | Nehme et al. 2022 [51]. |
Omalizumab (dose not mentioned) | 1 | Not described | Female, 55 years old. Allergic asthma, rhinoconjunctivitis. On lung transplant list | Improvement after the start. Withdrawal from transplant list | None after start | Withdrawal at 24 months | Not described | Not described | Not described | Not described | Laviña Soriano et al. 2017 [52]. |
300 mg every 4 weeks for 18 months, then decrease 50% every 6 months until discontinuation | 1 | 45 months | Female, 36 years old. Asthma Depression and steroid amenorrhea | Improvement after the start. a | None after the start. No relapses after 15 months of finishing the treatment | Tolerated descent and suspension at the 4th week | Resolution after treatment a | Not described | Not described | No adverse events during handling | Kaya & Tozkoparan 2012 [53]. Domingo & Pomares 2013 [54]. |
Doses | Number of participants | Duration of follow-up after biological | Age/sex/Comorbidities | Outcomes | Case report reference | ||||||
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Respiratory symptoms
| Relapses
| Systemic corticosteroid
| Radiological findings
| Lung function
| Quality of life
| Adverse events
| |||||
Dupilumab 300 mg every 2 weeks for 6 months | 1 | 12 months | Female, 11 years old. No response to antibiotic management, systemic steroids, or cyclosporine | Improvement at 2 weeks | None after start | Tolerated withdrawal and decrease in cyclosporine | Improvement at 2 weeks | Not described | Not described | No adverse events during handling | Fowler 2020 [55]. |