Proactive TDM Versus Standard Use of Biologics in Psoriasis

Официальное название

Proactive Therapeutic Drug Monitoring Versus Routine Care With the Novel Biologics in Psoriasis : a Pragmatic, Multicentric, Randomised, Controlled Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Proactive TDM-based dosing of secukinumab
  Maintenance/normal dose is 300 mg/4 weeks or 300 mg/ month 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
• Препарат 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
• Препарат 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

Первичные конечные точки

• Non-inferiority of sustained disease control [Срок оценки: 76 weeks]

Вторичные конечные точки (8)

• Psoriasis disease activity, measured with the Psoriasis Area and Severity Index (PASI) at each 12-weekly study visit. [Срок оценки: 76 weeks]
• Dermatology-related quality of life as measured with the Dermatology Life Quality Index (DLQI-R) at each 12-weekly study visit. [Срок оценки: 76 weeks]
• Health status of participants, assessed by using the Short Form 36 (SF-36) version 2 questionnaire at every 12-weekly time point. [Срок оценки: 76 weeks]
• Whether participants will have serious adverse events (SAE) and adverse events of special interest (AEoSI) during the study period. [Срок оценки: week 76]
• Pharmacokinetics of the drugs of interest [Срок оценки: 76 weeks]
• Immunogenicity of the drugs of interest [Срок оценки: 76 weeks]
• Utilities, derived from EuroQoL 5 Dimensions (EQ-5D-5L) questionnaires, which will be measured at each 12-weekly time point. [Срок оценки: 76 weeks]
• Volumes of care, as measured with the iMTA Medical Consumption Questionnaire (MCQ) at each 12-weekly time point. [Срок оценки: 76 weeks]

Критерии участия

Критерии включения

• Adults; aged 18 years or older
• Documented diagnosis of psoriasis (predominantly type vulgaris; based on clinical diagnosis) by an accredited dermatologist
• Patients must be currently treated with secukinumab, ixekizumab or guselkumab ≥ 6 months according to the standard dosing scheme.
• The subject signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures

Критерии исключения

• Another indication than plaque psoriasis as the main indication for biologic use (e.g. 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 tumour) or uncontrolled PsA at inclusion/baseline
• Presumed inability to follow the study protocol
• Active pregnancy wish

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бельгия · 15 центров

• AZ Sint-Jan — Bruges
• CHU Saint-Pierre — Brussels
• UCL Saint-Luc — Brussels
• ULB Erasme — Brussels
• UZ Brussel — Brussels
• Grand Hôpital de Charleroi — Charleroi
• AZ Alma — Eeklo
• Dermatologiepraktijk huidziekten Geel — Geel
• … и ещё 7 центров

Идентификаторы

NCT: NCT06398106 · ONZ-2024-0151 · 2023-509637-39-00 · KCE-22-1375

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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