OPTIMAL is a non-inferiority, open label randomized clinical trial thats investigates a titration algorithm for anti IL 5 biologics in severe asthma.

Inclusion Criteria:

• Informed written consent
• Age > 18 years
• Correct asthma diagnosis as judged by (sub)-investigator
• Treatment with anti-IL5/IL5r for 12 months or longer
• Treatment with the same biologic drug in the last 12 months
• No exacerbations requiring OCS in the last 12 months
• Blood eosinophils < 0.30 in the last 12 months
• No daily OCS for more than 3 days in the last 12 months with asthma as indication
• Correct inhalation technique for using regular inhalers
• Acceptable adherence to ICS (according to FMK as judged by (sub)-investigator)

Exclusion Criteria:

• - Pregnant or breastfeeding females
• Lack of effective contraception in women of childbearing potential who are sexually active with a non-sterilized male partner. Women of childbearing potential are defined as those who are not surgically sterile (e.g. bilateral tubal ligation, bilateral oophorectomy, complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Effective contraception is defined as intrauterine device (hormonal or non-hormonal), sexual abstinence, bilateral tubal occlusion, combined (estrogen and progesterone) hormonal contraception (oral, intravaginal and transdermal) and progesterone-only hormonal contraception (oral, injectable and implantable).
• Previous medical history or evidence of an uncontrolled intercurrent illness such as but not limited to (e.g. Autoimmune disease, immunodeficiency, immunosuppression, malignant neoplastic conditions with current relevance) that in the opinion of the investigator may compromise the safety of the subject in the study or interfere with evaluation of the algorithm or reduce the subject's ability to participate in the study. Subjects with well-controlled comorbid disease (eg, hypertension, hyperlipidaemia, gastroesophageal reflux disease) on a stable treatment regimen for 15 days prior to inclusion are eligible.
• Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the algorithm or interpretation of subject safety or study results (eg. chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, bronchiectasis, allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis polyangitiis, alpha-1-antitrypsin deficiency, Wegeners granulomatosis, Sarcoidosis).
• Any clinically relevant abnormal findings in haematology or clinical chemistry (laboratory results from Visit 0), physical examination, vital signs during the screening, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to participate in the study.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• History of chronic alcohol- or drug abuse 12 months prior to inclusion
• Concurrent enrolment in another clinical study involving an investigational treatment.
• Use of immunosuppressive medication (eg, methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroids or any experimental anti-inflammatory therapy) within 3 months prior to inclusion and during the study.