Proactive TDM Versus Standard Use of Biologics in Psoriasis

NCT ID: NCT06398106

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-20
• Study Completion Date: 2028-03-01

Brief Summary

Biologics are effective agents for the treatment of psoriasis. The newest generation of biologics block interleukin 17 and 23. Physicians always prescribe these drugs in a fixed dose, but this may lead to under- and overdosing in some patients. Underdosing may lead to inadequate response or loss of response over time. Overdosage, on the other hand, can lead to higher risk of side effects and higher costs for the healthcare system. In daily clinical practice, physicians often tackle this real-world issue by blind trial- and- error dose modifications or switching to another biologic. In this study, we want to rationalize these dose modifications and optimize dosing based on the drug concentrations, measured in the blood of the patient (i.e. therapeutic drug monitoring). Depending on the drug concentration, the interval between injections will be lengthened or shortened with the aim to reach the required drug concentration to reach the best clinical result. The trial will be conducted in 14 Belgian hospitals where patients will be divided into 2 study groups: a group that will be advised on the dosing scheme of their biologic based on the measured drug concentration and a group that continues dosing as in daily clinical practice. We will monitor if the clinical response and quality of life remains stable. With this study, we will track drug concentrations as we believe that they can guide dosing of biologics and we hope to achieve better safety, lower healthcare expenses and higher patients' treatment satisfaction while striving for the best clinical response.

Detailed Description

Rationale:

Biologics are effective agents for the treatment of psoriasis. The newest generation of biologics block interleukin 17 and 23. Physicians always prescribe these drugs in a fixed dose, but this may lead to under- and overdosing in some patients. Underdosing may lead to inadequate response or loss of response over time. Overdosage, on the other hand, can lead to higher risk of side effects and higher costs for the healthcare system. In daily clinical practice, physicians often tackle this real-world issue by blind trial- and- error dose modifications or switching to another biologic. In this study, we want to rationalize these dose modifications and optimize dosing based on the drug concentrations, measured in the blood of the patient (i.e. therapeutic drug monitoring).

Objectives: The primary goal is to assess if proactive TDM is non-inferior compared to standard of care with respect to sustained disease control, defined as an absolute PASI ≤ 2 OR a delta PASI from baseline ≥ 50% during at least 80% of all 3-monthly study visits over a period of 18 months, in patients with moderate to severe psoriasis treated with novel biologics (secukinumab, ixekizumab or guselkumab). Secondary goals are:

To compare proactive TDM to standard of care with respect to disease activity, quality of life, treatment satisfaction and costs of treatment (cost-effectiveness) To identify baseline predictors for sustained disease control. To evaluate the cost-effectiveness of proactive TDM To evaluate the safety of proactive TDM.

Study design: A multicentre, pragmatic, randomised, controlled, non-inferiority trial.

Study population:

Patients with moderate-to-severe psoriasis, treated with secukinumab or ixekizumab (IL-17 inhibitors) or guselkumab (IL-23 inhibitor) in daily clinical practice for at least 6 months on standard dosing (maintenance phase). A total of 210 patients will be randomized (1:1) to the intervention group (TDM based dosing) or continuation of usual care.

Intervention: Stepwise treatment modifications based on drug levels: if the drug level is below/above the target, the dose of the biologic will be increased/decreased by stepwise interval shortening/lengthening - first modified by 33% and then 50% increase or decrease. If the target is still not reached at the next study visit, the dosing interval will be shortened or prolonged with one additional week at each additional visit until the target is reached.

In case the dosing regimen shifts from dose increase to dose decrease or vice versa, the dosing interval will be shortened or prolonged with one additional week at each additional visit until the target is reached.

Conditions

Psoriasis Vulgaris

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard dosing of biologics

Patients will receive biological therapy according to standard clinical practice. Secukinumab, ixekizumab and guselkumab will be administered according to standard dosing regimen. Adjustments in doses and intervals, or biological switch according to clinical parameters or at the physicians' discretion are considered as standard clinical practice.

Investigators will not have access to information on levels of the drug or antidrug antibodies and no decision tree will be provided to guide treatment adjustments.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Proactive TDM based dosing

Stepwise treatment modifications based on drug levels: if the drug level is below/above the target the dose of the biologic will be increased/decreased by stepwise interval shortening/lengthening - first modified by 33% and then 50% increase or decrease. If the target is still not reached at the next study visit, the dosing interval will be shortened or prolonged with one additional week at each additional visit until the target is reached.

In case the dosing regimen shifts from dose increase to dose decrease or vice versa, the dosing interval will be shortened or prolonged with one additional week at each additional visit until the target is reached.

Group Type: EXPERIMENTAL

Proactive TDM-based dosing of secukinumab

Intervention Type: DRUG

Maintenance/normal dose is 300 mg/4 weeks.

First dose reduction step: 300 mg/6 weeks. Second dose reduction step: 300 mg/8 weeks. Further dose reduction steps: prolongation with 1 additional week

First dose escalation step: 300 mg/3 weeks Second dose escalation step: 300 mg/2 weeks Further dose escalation step: shortening with 1 additional week

Proactive TDM-based dosing of ixekizumab

Intervention Type: DRUG

Maintenance/normal dose is 80 mg/4 weeks.

First dose reduction step: 80 mg/6 weeks. Second dose reduction step: 80 mg/8 weeks Further dose reduction steps: prolongation with 1 additional week

First dose escalation step: 80 mg/3 weeks Second dose escalation step: 80 mg/2 weeks Further dose escalation step: shortening with 1 additional week

Proactive TDM-based dosing of guselkumab

Intervention Type: DRUG

Maintenance/normal dose is 100 mg/8 weeks.

First dose reduction step: 100 mg/12 weeks. Second dose reduction step: 100 mg/16 weeks. Further dose reduction steps: prolongation with 1 additional week

First dose escalation step: 100 mg/6 weeks Second dose escalation step: 100 mg/4 weeks Further dose escalation step: shortening with 1 additional week

Interventions

Proactive TDM-based dosing of secukinumab

Maintenance/normal dose is 300 mg/4 weeks.

First dose reduction step: 300 mg/6 weeks. Second dose reduction step: 300 mg/8 weeks. Further dose reduction steps: prolongation with 1 additional week

First dose escalation step: 300 mg/3 weeks Second dose escalation step: 300 mg/2 weeks Further dose escalation step: shortening with 1 additional week

Intervention Type: DRUG

Proactive TDM-based dosing of ixekizumab

Maintenance/normal dose is 80 mg/4 weeks.

First dose reduction step: 80 mg/6 weeks. Second dose reduction step: 80 mg/8 weeks Further dose reduction steps: prolongation with 1 additional week

First dose escalation step: 80 mg/3 weeks Second dose escalation step: 80 mg/2 weeks Further dose escalation step: shortening with 1 additional week

Intervention Type: DRUG

Proactive TDM-based dosing of guselkumab

Maintenance/normal dose is 100 mg/8 weeks.

First dose reduction step: 100 mg/12 weeks. Second dose reduction step: 100 mg/16 weeks. Further dose reduction steps: prolongation with 1 additional week

First dose escalation step: 100 mg/6 weeks Second dose escalation step: 100 mg/4 weeks Further dose escalation step: shortening with 1 additional week

Intervention Type: DRUG

Other Intervention Names

Cosentyx; Taltz; Tremfya

Eligibility Criteria

Inclusion Criteria

1. Adults; aged 18 years or older

2. Documented diagnosis of psoriasis (predominantly type vulgaris; based on clinical diagnosis) by an accredited dermatologist

3. Patients must be currently treated with secukinumab, ixekizumab or guselkumab ≥ 6 months according to the standard dosing scheme.

4. The subject signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures

Exclusion Criteria

1. Another indication than plaque psoriasis as the main indication for biologic use (e.g. receives biologic for rheumatoid arthritis as the main indication)

2. Concomitant use of systemic immunosuppressants other than methotrexate or acitretin (e.g. prednisone, cyclosporine etc)

3. Severe comorbidities with short life-expectancy (e.g. metastasized tumour) or uncontrolled PsA at inclusion/baseline

4. Presumed inability to follow the study protocol

5. Active pregnancy wish

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Belgium Health Care Knowledge Centre

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jo Lambert, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

AZ Sint-Jan

Bruges, , Belgium

Site Status: RECRUITING

UCL Saint-Luc

Brussels, , Belgium

Site Status: RECRUITING

ULB Erasme

Brussels, , Belgium

Site Status: NOT_YET_RECRUITING

UZ Brussel

Brussels, , Belgium

Site Status: NOT_YET_RECRUITING

Grand Hôpital de Charleroi

Charleroi, , Belgium

Site Status: NOT_YET_RECRUITING

AZ Alma

Eeklo, , Belgium

Site Status: NOT_YET_RECRUITING

Dermatologiepraktijk huidziekten Geel

Geel, , Belgium

Site Status: NOT_YET_RECRUITING

AZ Maria Middelares

Ghent, , Belgium

Site Status: RECRUITING

UZ Gent

Ghent, , Belgium

Site Status: RECRUITING

Clinique André Renard

Herstal, , Belgium

Site Status: RECRUITING

Dermatologie Handelskaai

Kortrijk, , Belgium

Site Status: RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status: NOT_YET_RECRUITING

Dermatologie Maldegem

Maldegem, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Jo Lambert, Prof

Role: CONTACT

jo.lambert@uzgent.be

093322298 ext. +32

Rani Soenen, Dr.

Role: CONTACT

rani.soenen@uzgent.be

093326541 ext. +32

Facility Contacts

Els Wittouck

Role: primary

Pierre-Dominique Ghislain, Prof.

Role: primary

Farida Benhadou

Role: primary

Jan Gutermuth

Role: primary

Pierre-Paul Roquet-Gravy, Dr.

Role: primary

Soetkin Desmet, Dr.

Role: primary

secr.dermato@azalma.be

Hugo Boonen, Dr.

Role: primary

Veerle Dhondt, Dr.

Role: primary

Jo Lambert, Prof.

Role: primary

Valérie Failla, Prof.

Role: primary

Erwin Suys, Dr.

Role: primary

Tom Hillary, Dr.

Role: primary

Sven Lanssens, Dr.

Role: primary

Related Links

https://psogent.ugent.be/projects.html

Website of the PsoGent research group

Other Identifiers

2023-509637-39-00

Identifier Type: CTIS

Identifier Source: secondary_id

KCE-22-1375

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ONZ-2024-0151

Identifier Type: -

Identifier Source: org_study_id