Table 1.
Articles examining the association of biological therapies in severe asthma.
| Author(s), Year | Study Type | Study Population |
Pathologies | Biologic Agents |
Follow Up | Efficacy | Safety |
|---|---|---|---|---|---|---|---|
| (A) Summary of the characteristics of the studies with dual biologic therapy for severe asthma insufficiently controlled with a biologic monotherapy. | |||||||
| Wechsler et al., 2021, [21] |
Phase II Trial | n = 74 | Severe asthma | DUP + ITE | 12 we | 27% of patients had an event indicating loss of asthma control, no increase in pre-bd FEV1, improved asthma control (ACQ and AQLQ) |
70% had AE, nasopharyngitis, allergic rhinitis, nausea, and back pain the most common |
| Serajeddini et al., 2023, [22] | Case series | n = 8 | Severe eosinophilic asthma (n = 8) | BEN + DUP (n = 4) MEP + DUP (n = 2) RES + DUP (n = 2) |
Median: 10 mo |
Significant improvement in clinical, functional, and inflammatory parameters (full data provided). 2 patients did not receive complete symptoms control | No AE reported |
| Thomes and Darveaux, 2018, [23] abstract only |
Case series | n = 3 | Severe allergic and eosinophilic asthma | OMA + MEP | Unknown | Reduced number of exacerbations, tapered daily OCS dose and provided a better control of symptoms. |
Unknown |
| Baccelli et al., 2022, [24] | Case report | 68 yo F | Severe allergic and eosinophilic asthma | OMA + MEP | 3 y | Reduced BEC (200 vs. 2330 cells/mcl), increased exercise capacity (6MWT 280 vs. 160 m) and lung function (FEV1 1.32 vs. 1.08 L), improvement in QOL, reduced exacerbations, reduced daily OCS and SABA use. | No AE reported |
| Dedaj and Unsel, 2018, [25] | Case report | 55 yo F | Severe allergic and eosinophilic asthma | OMA + MEP | 6 mo | Reduced OCS daily dose, reduced exacerbations and no ER visit or hospitalization | No AE reported |
| Bergmann et al., 2022, [26] |
Case report | 53 yo M | Severe allergic and eosinophilic asthma |
OMA + MEP OMA + BEN |
17 mo >7 mo |
OCS and LTOT discontinued, improvement of exercise capacity at 6MWT, improved QOL. | No AE reported |
| Domingo et al., 2020, [27] |
Case report | 55 yo F | Severe allergic and eosinophilic asthma |
OMA + MEP | 24 mo | Improvement in the FEV1 (96% pred. vs. 22% pred.), OCS dose reduction. |
No side effects observed |
| Sezgin et al., 2023, [28] | Case report | 52 yo M | Severe allergic asthma | OMA + MEP | Unknown | Improvement in the control of symptoms, improved QOL and increased respiratory function. OCS stopped. |
No side effects observed |
| Fox and Rotolo, 2021, [29] |
Case report | 12 yo F | Severe allergic and eosinophilic asthma |
OMA + MEP | 24 mo | Weaned off OCS, improvement in QOL |
Mild headache |
| Phan et al., 2018, [30] abstract only |
Case report | 16 yo F | Severe allergic asthma, allergic rhinitis |
OMA + MEP | 4 mo | Symptoms improved, higher QOL. |
No AE observed |
| (B) Summary of the characteristics of the studies with cycling biologic therapy for severe asthma. | |||||||
| Hamada et al., 2021, [31] | Case report | 43 yo F | Severe eosinophilic asthma, ECRS, EOM | BEN + DUP as Cycling Therapy |
11 mo | No new exacerbations, SABA and OCS not used, BEC = 0, Lund-Mackay score decreased to zero, reduction of FeNO levels |
No AE reported |
| Hamada et al., 2021, [32] | Case report | 47 yo M | Severe allergic and eosinophilic asthma, CRSwNP |
MEP + DUP as Cycling Therapy |
12 mo | No emergency department visits or hospital admissions, SABA and OCS not used, no decrease in ACT or elevation in eosinophil count, Lund-Mackay score decreased to zero |
No adverse effects occurred |
| (C) Summary of the characteristics of the studies with dual biologic therapy for uncontrolled severe asthma and type 2 comorbidities | |||||||
| Pitlick and Pongdee, 2022, [33] | Case series | n = 25 | Severe asthma: 10 patients Severe asthma and CRSwNP: 1 patient Severe asthma and EGPA: 1 patient Severe asthma and CSU: 1 patient T2 comorbidities: 12 patients |
OMA + MEP (n = 11) OMA + DUP (n = 6) OMA + BEN (n = 4) MEP + DUP (n = 3) OMA + DUP + MEP (n = 1) |
1–60 mo Median: 17.5 mo |
Unknown | No AE reported |
| Lommatzsch et al., 2022, [34] | Case series | n = 25 * | Severe asthma: 7 patients Severe asthma and AD: 2 patients Severe asthma and CSU: 1 patient Severe asthma and EGPA: 1 patient Severe asthma and CRSwNP: 4 patients |
BEN + DUP (n = 5) DUP + MEP (n = 3) OMA + DUP (n = 2) OMA + MEP (n = 2) BEN + OMA (n = 1) MEP/BEN + OMA (n = 1) OMA + RES/MEP (n = 1) |
3–38 mo Median: 9 mo |
Improvement in ACT and FEV1, reduced or stopped OCS use. Interrupted in 4 patients for ineffectiveness |
No AE reported |
| Otten et al., 2023, [35] | Retrospective observational study |
n = 7 | Severe eosinophilic asthma and CRSwNP: 7 patients |
DUP + BEN (n = 4) DUP + MEP (n = 2) RES + DUP (n = 1) |
Unknown | Unknown | Unknown |
| Ortega et al., 2019, [36] | Case series | n = 3 | Severe allergic and eosinophilic asthma and multiple type 2 comorbidities AD, allergic rhinitis, ABPA: 1 patient CSU, allergic rhinitis, CRSwNP: 1 patient CRSwNP, ABPA, allergic conjunctivitis: 1 patient |
OMA + DUP (n = 1) OMA + MEP/BEN (n = 2) |
9 mo Pt.1 31 mo Pt.2 19 mo Pt.3 |
OCS stopped, better control of symptoms. Pt. 3 was hospitalized for an exacerbation and switched from OMA + BEN to DUP monotherapy. | No AE reported |
| Caskey and Kaufman, 2021, [37] | Case report | 51 yo M | Severe eosinophilic asthma, CSU | MEP + OMA | 4 y | Improvement in urticaria symptoms and QOL. Asthma controlled, no OCS required, no additional FEV1 improvement. | No AE reported |
| Volpato et al., 2020, [38] | Case report | 60 yo M | Severe eosinophilic asthma, CSU | MEP + OMA | 3 y | Stopped OCS use, improvement in FEV1 (86 vs. 73% pred), no skin itching or anaphylactic manifestation. No new hospitalizations, one mild exacerbation. | No AE reported |
| Nicolaides and Khan, 2019, [39] abstract only |
Case report | 50 yo F | Severe asthma, AERD, CRSwNP, urticaria |
BEN + OMA | >2 mo | Improved control of both urticaria and asthma symptoms, reduced need for OCS. | No AE observed |
| Can Bostan et al., 2023, [40] |
Case report | NA | Severe asthma, urticaria |
OMA + MEP | 6 mo | Both diseases controlled |
No AE reported |
| Tongchinsub and Carr, 2017, [41] abstract only |
Case report | 56 yo F | Severe eosinophilic asthma, CRSwNP, eosinophilic mastoiditis |
OMA + MEP | 5 mo | Stopped OCS use. | No AE reported |
| Han and Lee, 2018, [42] | Case report | 67 yo F | Severe asthma, EoE | MEP + OMA | Unknown | Improvement of asthma and GI symptoms, OCS stopped. | No AE reported |
| Laorden et al., 2022, [43] |
Case series | n = 3 | Severe asthma and ABPA: 3 patients | OMA + BEN (n = 2) OMA + MEP (n = 1) |
2 y | Improvement of asthma symptoms, no exacerbations, improvement of lung function, reduction of OCS. | No AE reported |
| Curtiss et al., 2023, [44] abstract only |
Case series | n = 2 | Severe asthma and ABPA | DUP + MEP DUP + BEN |
Unknown | Weaned daily OCS dose. Improvement of asthma symptoms and decreased exacerbation frequency. 1 mild exacerbation. |
No AE reported |
| Altman et al., 2017, [45] | Case report | 58 yo F | Severe asthma and ABPA | OMA + MEP | 7 mo | Full return of ADLs, discontinuation of OCS and supplemental oxygen, reduced BEC (0 vs. 1100 cells/mcl) and IgE (298 vs. 1730 IU/mL). |
No AE reported |
| (D) Summary of the characteristics of the studies with dual biologic therapy for dupilumab induced hypereosinophilia and eosinophils related disorders | |||||||
| Descamps et al., 2021, [46] | Case report | 61 yo F | Severe asthma, CRSwNP, dupilumab induced eosinophilic vasculitis | DUP + BEN | >16 mo | Complete and stable eosinophil depletion, skin lesions completely healed, no new vasculitic manifestations. |
No AE reported |
| Anai et al., 2022, [47] | Case report | 42 yo M | Severe asthma, EGPA | MEP + DUP | >16 we | Reduced symptoms, FEV1 improvement (4.43 vs. 3.84 L), reduced FeNO levels and BEC. | No AE reported |
| Philipenko et al., 2020, [48] abstract only |
Case report | 28 yo M | Severe eosinophilic asthma, AD, dupilumab induced conjunctivitis | DUP + MEP | Unknown | Reduction of BEC, improvement in ACQ, no asthma exacerbations, conjunctivitis resolved. | No AE reported |
| Briegel et al., 2021, [49] | Case report | 24 yo F | EGPA, CRSwNP |
DUP + BEN | 1.5 y | Improvement of pulmonary and nasal symptoms, reduction of OCS daily dose. | No AE reported |
* 10 patients received a dual biologic therapy with a biologic approved for severe asthma and a second biologic drug for another concomitant disease. ABPA—allergic bronchopulmonary aspergillosis; ACT—Asthma Control Test; ACQ—Asthma Control Questionnaire; AD—atopic dermatitis; ADLs—activities of daily living; AE—adverse event; AERD—aspirin exacerbated respiratory disease; AQLQ—Asthma Quality of Life Questionnaire; BEC—blood eosinophil count; BEN—benralizumab; CRSwNP—chronic rhinosinusitis with nasal polyposis; CSU—chronic spontaneous urticaria; DUP—dupilumab; ECRS—eosinophilic chronic rhinosinusitis; EGPA—eosinophilic granulomatosis with polyangiitis; EoE—eosinophilic esophagitis; EOM—eosinophilic otitis media; ER—emergency room; F—female; FeNO—fractional exhaled nitric oxide; FEV1—forced expiratory volume in 1 s; ITE—itepekimab; LTOT—long term oxygen therapy; M—male; MEP—mepolizumab; mo—months; NA—not available; OMA—omalizumab; OCS—oral corticosteroids; QOL—quality of life; RES—reslizumab; SABA—short acting β2 agonist; y—year; yo—year old; we—weeks; 6MWT—6 min walking test.