Clinical trial NCT02602925: Tight Control Dose Reductions of Biologics in Psoriasis Patients With Low Disease Activity
Official title: Tight Control Dose Reductions of Biologics in Psoriasis Patients With Low Disease Activity: A Randomized Pragmatic Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psoriasis
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2015-11-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled non-inferiority study
Primary purpose: TREATMENT

Brief summary: Rationale/hypothesis: Moderate-to-severe psoriasis can be treated with biologics.

Objective To investigate whether the dose of biologics can be reduced in patients with psoriasis with stable disease.

Study design: A pragmatic, multicentre, randomized, controlled, non-inferiority study with cost-effectiveness analysis.

Study population: Patients with disease remission using normal dose of biologics.

Intervention: 120 patients will be randomized into two groups: (1) dose reduction and (2) normal dose.

Main study parameters/endpoints: The primary outcome is clinical effectiveness. Secondary outcomes are: health-related quality of life (HRQoL), number and time to disease flares, costs, health status, anti-drug antibody formation and serious adverse events

Detailed description: Rationale/hypothesis: Moderate-to-severe psoriasis can be treated with biologics. These drugs have significantly improved the quality of life of psoriasis patients, but are very expensive drugs that should be used as efficiently as possible. In addition, the long-term safety profile can probably be improved if patients receive the lowest effective dose.

Objective To investigate whether the dose of biologics can be reduced in patients with psoriasis with stable disease: Is dose reduction non-inferior to the current practice regarding clinical effectiveness? Secondary aims are: to investigate what influence dose tapering has on quality of life, whether there are predictors for successful dose reduction, and to determine the cost-effectiveness of dose reduction.

Study design: A pragmatic, multicentre, randomized, controlled, non-inferiority study with cost-effectiveness analysis.

Study population: Patients who used a biologic for at least 6 months (etanercept, adalimumab, ustekinumab) can be included if they have long-term stable low disease activity. Low disease activity is defined as a PASI score (Psoriasis Area and Activity Score) \<5 and a health-related quality of life score ≤5 (Dermatology Quality of life index: DLQI).

Intervention: 120 patients will be randomized into two groups: (1) dose reduction guided by PASI and DLQI (n=60, intervention) and (2) maintenance of normal dosage (n=60, usual care).

Main study parameters/endpoints: The primary outcome is clinical effectiveness. Secondary outcomes are: health-related quality of life (HRQoL), number and time to disease flares, costs, health status, anti-drug antibody formation and serious adverse events

Eligibility criteria: Inclusion Criteria:

* Sustained low disease activity as described above on the dose as advised by the label.
* Established diagnosis of plaque psoriasis.
* Receiving treatment with adalimumab, etanercept, or ustekinumab for at least 6 months.\*
* Age ≥18 years.
* Ability to understand informed consent, read and answer questionnaires.

Exclusion Criteria:

* Psoriasis itself is not the main reason for biologic prescription (e.g. when a patient has RA and psoriasis, and RA is the main reason for the biologic).
* Concomitant use of immunosuppressants other than methotrexate or acitretin for psoriasis.
* Severe comorbidities with short life-expectancy (e.g. metastasized tumour).
* Presumed inability to follow the study protocol.

Primary outcomes:
measure: Disease-activity
timeFrame: 1 year
Secondary outcomes:
measure: Health-related quality of life (HRQoL-DLQI)
timeFrame: 1 year
measure: Number of patients with 1 or more persistent flares
timeFrame: 1 year
measure: Disease-activity measured with HsCRP
timeFrame: 1 year
measure: Predictors for succesful dose decrease (treatment and patient characteristics)
timeFrame: 1 year
measure: Anti-drug antibody levels against etanercept, adalimumab or ustekinumab
timeFrame: 1 year
measure: Drug trough levels of etanercept, adalimumab or ustekinumab
timeFrame: 1 year
measure: Number of serious adverse events per patient
timeFrame: 1 year
measure: Costs related to medical consumption
timeFrame: 1 year
measure: Costs related to productivity
timeFrame: 1 year
measure: Health status (SF36)
timeFrame: 1 year
Other outcomes:
Locations:
city: Almelo
country: Netherlands
facility: ZGT hospital
city: Apeldoorn
country: Netherlands
facility: Gelre hospitals
city: Doetinchem
country: Netherlands
facility: Slingeland Hospital
city: Geldrop
country: Netherlands
facility: St. Anna hospital
city: Hengelo
country: Netherlands
facility: ZGT
city: Nijmegen
country: Netherlands
facility: Radboudumc, dept of dermatology
Study officials:
affiliation: Dept. of Dermatology, Radboudumc, The Netherlands
name: E de Jong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atalay S, van den Reek JMPA, den Broeder AA, van Vugt LJ, Otero ME, Njoo MD, Mommers JM, Ossenkoppele PM, Koetsier MI, Berends MA, van de Kerkhof PCM, Groenewoud HMM, Kievit W, de Jong EMGJ. Comparison of Tightly Controlled Dose Reduction of Biologics With Usual Care for Patients With Psoriasis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Apr 1;156(4):393-400. doi: 10.1001/jamadermatol.2019.4897.
citation: Atalay S, van den Reek JMPA, van Vugt LJ, Otero ME, van de Kerkhof PCM, den Broeder AA, Kievit W, de Jong EMGJ. Tight controlled dose reduction of biologics in psoriasis patients with low disease activity: a randomized pragmatic non-inferiority trial. BMC Dermatol. 2017 May 8;17(1):6. doi: 10.1186/s12895-017-0057-6.