Relationship Between the Response to Antibody Therapy and Symptoms of Depression and Anxiety Disorders in Patients with Severe Asthma

Abstract

Purpose

Asthma is associated with a high prevalence of psychopathological disorders, especially depressive disorders or anxiety. In patients with uncontrolled severe asthma, monoclonal antibody (mAb)-therapy positively influenced control of mental disorders. Therefore, we evaluated the impact of antibody therapy on the burden of these mental diseases depending on responder status.

Patients and Methods

Data were collected retrospectively in patients with uncontrolled severe asthma (n = 82) prior to mAb-therapy (“baseline”) (omalizumab, dupilumab, benralizumab or mepolizumab). Symptoms of Major Depressive Disorder (MDD) or General Anxiety Disorder (GAD) were detected at baseline using the Hospital Anxiety and Depression Scale (HADS), as well as general sociodemographic data and lung function parameters. At 6-month (±3 month) follow-up, the burden of psychopathological symptoms under mAb-therapy was assessed using the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder Scale-2 (GAD-2). Response status was classified using the Biologics Asthma Response Score (BARS), assessing exacerbations, oral corticosteroid usage and asthma control test (ACT) score. Predictors for non-response to mAb-therapy were identified using linear regression analysis.

Results

Patients with severe asthma suffered from symptoms of MDD/GAD more often compared to the general population, with a higher prevalence among mAb therapy non-responders. mAb-responders exhibited a declining burden of MDD, better quality of life (QoL), less exacerbations, better lung function and better disease control compared to non-responders. A history of symptoms of depression was identified as a predictor for non-response to mAb-therapy.

Conclusion

Asthma symptoms and psychological problems are linked and more prevalent in our cohort of severe asthma patients than in the general population. Patients with signs of MDD/GAD before mAb-therapy show less mAb therapy response suggesting a negative impact of prior psychological problems on treatment response. In some patients, the score on MDD/GAD was caused by severe asthma – here symptoms decreased after effective treatment.

Keywords:

• severe asthma
• monoclonal antibody therapy
• depression
• anxiety
• therapy response

Abbreviations

mAb, monoclonal antibody; MDD, Major Depression Disorder; GAD, General Anxiety Disorder; HADS, Hospital Anxiety and Depression Scale; PHQ-2, Patient Health Questionnaire-2; GAD-2, General Anxiety Disorder-2; CTEPH, Chronic thromboembolic pulmonary hypertension; QoL, Quality of Life; ACT, Asthma Control Test; ERS, European respiratory society; ATS, American thoracic society; FDA, Food and Drug agency; EMA, European Medicines agency; COPD, Chronic obstructive pulmonary disease; OCS, Oral corticosteroids; Audit-C-Score, Alcohol Use Disorders Identification Test; CI, Confidence interval; OR, Odds ratio; BMI, Body Mass Index; FEV₁, Forced expiratory volume; IgE, Immunoglobulin E; MCID, minimum clinically important difference; BL, Baseline; FU, Follow-Up; IQR, Interquartile range.

Data Sharing Statement

Data used in this study are available on reasonable request by the corresponding author.

Ethics Approval and Consent to Participate

Approval of the local ethic committee of the Hannover Medical School (10539_BO_K_2022) was given and all patients provided written informed consent allowing the use of their data for scientific research.

Acknowledgments

We wish to thank all patients who participated in this project. We would also like to thank the clinical staff caring about the patients and the questionnaires and last but not least the families of the authors who have given up a lot of time with their loved ones to make this research possible.

Disclosure

Tobias Welte and/or his institution received grants advisory/lecture/clinical trial fees and non-financial support by DFG (German Research Council), BMBF (German Ministry of Research and Education), BMG (German Ministry of Health), EU, WHO, AstraZeneca, Basilea, Biotest, Bayer, Boehringer, Berlin Chemie, GSK, Infectopharm, MSD, Novartis, Pfizer, Roche, AstraZeneca, Basilea, Biotest, Bayer, Boehringer, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, German Center of Lung Research all outside the submitted work. Hendrik Suhling reports personal fees/speaker honoraria from AstraZeneca, GSK, Novartis, Sanofi, outside the submitted work. Jan Fuge reports personal fees/speaker honoraria from AstraZeneca outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

There is no funding to report.