Clinical trial NCT04340076: Dose Reduction of IL17 and IL23 Inhibitors in Psoriasis
Official title: Dose Reduction of the New Generation Biologicals (IL17 and IL23 Inhibitors) in Psoriasis: A Pragmatic, Multicentre, Randomized, Controlled, Non-inferiority Study - BeNeBio Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Psoriasis
Psoriasis Vulgaris
Keywords: skin diseases
skin diseases (papulosquamous)
biologicals
IL17 inhibitors
IL23 inhibitors
dose reduction
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Belgium Health Care Knowledge Centre
name: University Hospital, Ghent
First posted: 2020-04-09
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multicentre, pragmatic, randomized, controlled, non-inferiority trial. Patients will be randomized 2:1 to dose reduction and usual care.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Non-inferiority of the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months).
timeFrame: 18 months
Secondary outcomes:
measure: Whether participants will have successful DR after 12 and 18 months, defined as using a lower dose than the normal dose and PASI ≤ 5.
timeFrame: 18 months
measure: Psoriasis disease activity, measured with the Psoriasis Area and Severity Index (PASI) at each 3-monthly study visit.
timeFrame: 18 months
measure: Dermatology-related quality of life as measured with the Dermatology Life Quality Index (DLQI) at each 3-montly study visit.
timeFrame: 18 months
measure: Whether participants will have short disease flares throughout the study period (18 months), defined as a PASI > 5 at one time point.
timeFrame: 18 months
measure: Whether other anti-psoriatic medication will be initiated in participants during the study period (18 months).
timeFrame: 18 months
measure: Whether participants will have serious adverse events (SAE) and adverse events of special interest (AEoSI) during the study period.
timeFrame: 18 months
measure: Drug trough levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point.
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
measure: Utilities, derived from EuroQoL 5 Dimensions (EQ-5D-5L) questionnaires, which will be measured at each 3-montly time point.
timeFrame: 18 months
measure: Health status of participants, assessed by using the Short Form 36 (SF-36) version 2 questionnaire at every 3-monthly time point.
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: ULB Erasme
city: Gent
country: Belgium
facility: Ghent University Hospital
city: Ghent
country: Belgium
facility: AZ Maria Middelares
city: Ghent
country: Belgium
facility: AZ St Lucas
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU Liege
city: Louvain
country: Belgium
facility: UCL Saint Luc
city: Maldegem
country: Belgium
facility: Dermatologie Maldegem
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Bergen Op Zoom
country: Netherlands
facility: Bravis hospital
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Doetinchem
country: Netherlands
facility: Slingeland hospital
city: Eindhoven
country: Netherlands
facility: Catharina hospital
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Veldhoven
country: Netherlands
facility: Máxima Medisch Centrum
Study officials:
affiliation: Radboud University Medical Center
name: Elke de Jong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van der Schoot LS, van den Reek JMPA, Grine L, Schots L, Kievit W, Lambert JLW, de Jong EMGJ. Dose reduction of the new generation biologics (IL-17 and IL-23 inhibitors) in psoriasis: study protocol for an international, pragmatic, multicenter, randomized, controlled, non-inferiority study-the BeNeBio study. Trials. 2021 Oct 16;22(1):707. doi: 10.1186/s13063-021-05681-z.