Proactive TDM versus standard use of biologics in psoriasis (HELIOS)

Phase 4

Recruiting

Conditions: moderate-to-severe psoriasis

Registration Number: 2023-509637-39-00

Lead Sponsor: Universitair Ziekenhuis Gent

Brief Summary: 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).

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.

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 210

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is 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.		The primary endpoint is 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.

Secondary Outcome Measures

Name	Time	Method
● Cost of treatment (medication used and cost of TDM)		● Cost of treatment (medication used and cost of TDM)
● Healthcare consumption (iMCQ)		● Healthcare consumption (iMCQ)
● Number of dose modifications during the 18 months (0 – 6)		● Number of dose modifications during the 18 months (0 – 6)
● Change from baseline at 18 months in PASI score. The PASI measures disease activity. The scores ranges from 0 (skin lesion free) to 72 with higher scores indicating higher disease activity.		● Change from baseline at 18 months in PASI score. The PASI measures disease activity. The scores ranges from 0 (skin lesion free) to 72 with higher scores indicating higher disease activity.
● Change from baseline at 18 months in DLQI_R score. The DLQI_R measures QoL. The score ranges from 0 (no impact) to 30 (greatest impact) with higher scores indicating higher impact on quality of life.		● Change from baseline at 18 months in DLQI_R score. The DLQI_R measures QoL. The score ranges from 0 (no impact) to 30 (greatest impact) with higher scores indicating higher impact on quality of life.
● Change from baseline at 18 months in SF-36 score. The SF-36 measures QoL. The score ranges from 0 (maximum disability) to 100 (no disability). In the field of dermatology, the SF36 has been proposed as the instrument of choice for evaluating QoL in a generic way by Both et al.. Although we acknowledge that the SF36 can be perceived as more difficult to fill in by the patients, comparison of QoL measures by Fernandez-Penas et al, showed that SF‐36 was more sensitive than other instruments in d		● Change from baseline at 18 months in SF-36 score. The SF-36 measures QoL. The score ranges from 0 (maximum disability) to 100 (no disability). In the field of dermatology, the SF36 has been proposed as the instrument of choice for evaluating QoL in a generic way by Both et al.. Although we acknowledge that the SF36 can be perceived as more difficult to fill in by the patients, comparison of QoL measures by Fernandez-Penas et al, showed that SF‐36 was more sensitive than other instruments in d
● New onset or flare of arthritis		● New onset or flare of arthritis
● Drug discontinuation (incl. reasons)		● Drug discontinuation (incl. reasons)
● Serious adverse events (SAE)		● Serious adverse events (SAE)
● Adverse events of special interest (AEoSI) ○ occurrence of infusion reactions ○ infections		● Adverse events of special interest (AEoSI) ○ occurrence of infusion reactions ○ infections
● Change from baseline at 18 months in TSQM score. The TSQM measures treatment satisfaction. TSQM is a 9-point questionnaire with scores ranging from 0 to 100. Higher scores indicate higher satisfaction.		● Change from baseline at 18 months in TSQM score. The TSQM measures treatment satisfaction. TSQM is a 9-point questionnaire with scores ranging from 0 to 100. Higher scores indicate higher satisfaction.
● Change from baseline at 18 months in VAS score. The VAS measures treatment satisfaction. The VAS is a horizontal line of 100mm, with scores ranging from 0 (no satisfaction) to 10 (extreme satisfaction).		● Change from baseline at 18 months in VAS score. The VAS measures treatment satisfaction. The VAS is a horizontal line of 100mm, with scores ranging from 0 (no satisfaction) to 10 (extreme satisfaction).
● iMCQ and EQ-5D-5L to measure cost-effectiveness. Shikiar et al. showed that the EQ-5D index score is generally more highly correlated with clinical endpoints, compared with the SF-36, but displayed about the same degree of responsiveness. The MCID for the EQ-5D score is considered 6 units.		● iMCQ and EQ-5D-5L to measure cost-effectiveness. Shikiar et al. showed that the EQ-5D index score is generally more highly correlated with clinical endpoints, compared with the SF-36, but displayed about the same degree of responsiveness. The MCID for the EQ-5D score is considered 6 units.

Trial Locations

Locations (14): Fonds et Services Sociaux Reseau Solidaris
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Herstal, Belgium
Cliniques Universitaires Saint-Luc
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Sint-Lambrechts-Woluwe, Belgium
DERMATOLOGIEPRAKTIJK HUIDZIEKTEN GEEL
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Geel, Belgium
ASSOCIATIE DERMATOLOGIE Suys Erwin en Bonny Michiel FV
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Kortrijk, Belgium
Grand Hopital De Charleroi
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Gerpinnes, Belgium
Az St-Jan Brugge-Oostende A.V.
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Brugge, Belgium
Algemeen Ziekenhuis Alma
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Eeklo, Belgium
Universitair Ziekenhuis Gent
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Gent, Belgium
Hopital Erasme
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Anderlecht, Belgium
Universitair Ziekenhuis Brussel
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Jette, Belgium
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Fonds et Services Sociaux Reseau Solidaris
🇧🇪Herstal, Belgium
Valérie Failla
Site contact
042487305
valerie.failla@andrerenard.be