Dose Reduction of IL17 and IL23 Inhibitors in Psoriasis
- Conditions
- PsoriasisPsoriasis Vulgaris
- Interventions
- Registration Number
- NCT04340076
- Lead Sponsor
- Radboud University Medical Center
- Brief Summary
The main objective of this study is to investigate whether controlled dose reduction of IL17 or IL23 inhibiting biologics is not inferior compared to usual care in psoriasis patients. Therefore, a pragmatic, multicentre, randomized, controlled, non-inferiority study will be carried out.
- Detailed Description
Rationale: Biologics are very effective treatments for psoriasis. Research indicated that the dose of TNFα-blocking biologics can be reduced in a proportion of patients. Safety profiles can improve and costs can be reduced if the reduction of the dose is successful. Recently, the newest generation of biologics entered the market: interleukin (IL) 17 and IL23 inhibitors. It is not yet known whether dose reduction of these agents is possible, and to what extent they can be reduced. The timely investigation of the possibilities for dose reduction of new biologics is therefore important.
Objectives: The primary goal is to investigate whether controlled dose reduction of IL17 or IL23 inhibiting biologics is not inferior compared to usual care. This is measured by comparing the proportion of long-term disease flares between the two groups (dose reduction group versus usual care group). Secondary goals are: determining the proportion of patients with successful dose reduction, clinical effectiveness measured with the Psoriasis Area and Severity score (PASI) score, Dermatology Life Quality Index (DLQI) scores, predictors for successful dose reduction, safety, and cost-effectiveness of dose reduction. Pharmacokinetic (PK) analysis will be performed for modeling.
Study design: a multicenter, practice-oriented, pragmatic, randomized, controlled, non-inferiority study.
Study population: Patients treated with the newest generation of biologics (IL17 or IL23 inhibitors), with long-term stable low disease activity at a normal dose. A total of 244 patients will be randomized (2:1) to dose reduction or continuation of usual care.
Intervention: Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 244
- Plaque psoriasis (primarily)
- Treatment for at least 6 months with IL23 or IL17 inhibitor in a normal dose (dose advised by the label)
- PASI≤ 5 at inclusion and in previous 6 months (if no PASI scores are available, it should be clear from the patient record that psoriasis was clear/almost clear in previous 6 months).
- DLQI ≤ 5 at inclusion
- Another indication than plaque psoriasis as the main indication for biologic use (e.g. patient receives biologic for rheumatoid arthritis as the main indication).
- Concomitant use of systemic immunosuppressants other than methotrexate or acitretin (e.g. prednisone, cyclosporine etc).
- Severe comorbidities with short life-expectancy (e.g. metastasized tumor).
- Presumed inability to follow the study protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose reduction Ixekizumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low. Normal dose Bimekizumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Dose reduction Secukinumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low. Dose reduction Brodalumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low. Dose reduction Tildrakizumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low. Dose reduction Guselkumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low. Normal dose Ixekizumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Normal dose Brodalumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Normal dose Secukinumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Normal dose Guselkumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Normal dose Tildrakizumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Dose reduction Risankizumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low. Normal dose Risankizumab Patients will continue treatment with the normal/maintenance dose of the biologicals. Dose reduction Bimekizumab Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
- Primary Outcome Measures
Name Time Method Non-inferiority of the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months). 18 months
- Secondary Outcome Measures
Name Time Method Whether other anti-psoriatic medication will be initiated in participants during the study period (18 months). 18 months Drug trough levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point. 18 months Utilities, derived from EuroQoL 5 Dimensions (EQ-5D-5L) questionnaires, which will be measured at each 3-montly time point. 18 months Utility scores will be used to calculate quality adjusted life years (QALYs) which are used to determine cost-effectiveness of DR.
Psoriasis disease activity, measured with the Psoriasis Area and Severity Index (PASI) at each 3-monthly study visit. 18 months Dermatology-related quality of life as measured with the Dermatology Life Quality Index (DLQI) at each 3-montly study visit. 18 months Whether participants will have successful DR after 12 and 18 months, defined as using a lower dose than the normal dose and PASI ≤ 5. 18 months Definition of successful dose reduction: lower dose than the normal dose and PASI≤ 5.
Whether participants will have short disease flares throughout the study period (18 months), defined as a PASI > 5 at one time point. 18 months Whether participants will have serious adverse events (SAE) and adverse events of special interest (AEoSI) during the study period. 18 months AEoSI include, but are not limited to, infections, malignancies, and joint complaints or new-onset psoriatic arthritis.
Anti-drug antibody levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point. 18 months Loss of productivity and presenteeism of participants, as measured with the iMTA Productivity Cost Questionnaire (PCQ) at each 3-monthly time point. Scores will be used to calculate direct medicals costs and non-medical costs. 18 months Health status of participants, assessed by using the Short Form 36 (SF-36) version 2 questionnaire at every 3-monthly time point. 18 months Volumes of care, as measured with the iMTA Medical Consumption Questionnaire (MCQ) at each 3-monthly time point. Scores will be used to calculate direct medicals costs and non-medical costs. 18 months
Trial Locations
- Locations (19)
Amphia Hospital
🇳🇱Breda, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Máxima Medisch Centrum
🇳🇱Veldhoven, Netherlands
UMC Groningen
🇳🇱Groningen, Netherlands
UZ Leuven
🇧🇪Leuven, Belgium
Dermatologie Maldegem
🇧🇪Maldegem, Belgium
Ziekenhuisgroep Twente
🇳🇱Almelo, Netherlands
Bravis hospital
🇳🇱Bergen Op Zoom, Netherlands
Ghent University Hospital
🇧🇪Gent, Belgium
Maastricht UMC
🇳🇱Maastricht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands
AZ St Lucas
🇧🇪Ghent, Belgium
UCL Saint Luc
🇧🇪Louvain, Belgium
AZ Maria Middelares
🇧🇪Ghent, Belgium
CHU Liege
🇧🇪Liège, Belgium
Catharina hospital
🇳🇱Eindhoven, Netherlands
Slingeland hospital
🇳🇱Doetinchem, Netherlands
ULB Erasme
🇧🇪Brussels, Belgium