Tight Control Dose Reductions of Biologics in Psoriasis Patients With Low Disease Activity

Psoriasis Clinical Trial

Official title:

Tight Control Dose Reductions of Biologics in Psoriasis Patients With Low Disease Activity: A Randomized Pragmatic Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02602925
• Other study ID #: CONDOR
• Status: Completed
• Phase: Phase 4
• Start date: March 2016
• Est. completion date: July 20, 2018

Study information

• Verified date: November 2016
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: July 20, 2018
• Est. primary completion date: July 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Other:
• Dose decrease
Treatment strategy change: dose decrease based on PASI and DLQI
• Usual care
Usual care

Locations

Country	Name	City	State
Netherlands	ZGT hospital	Almelo
Netherlands	Gelre hospitals	Apeldoorn
Netherlands	Slingeland Hospital	Doetinchem
Netherlands	St. Anna hospital	Geldrop
Netherlands	ZGT	Hengelo
Netherlands	Radboudumc, dept of dermatology	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-activity	Disease-activity measured by Psoriasis Area and Severity Index (PASI), effectiveness measure used in most psoriasis trials.	1 year
Secondary	Health-related quality of life (HRQoL-DLQI)	HRQoL(Dermatology Life Quality Index (DLQI)	1 year
Secondary	Number of patients with 1 or more persistent flares	Number of patients with 1 or more persistent flares (persistent flare is defined as at least 3 months PASI increase >5 or DLQI >5)	1 year
Secondary	Disease-activity measured with HsCRP	High-sensitivity CRP, a possible marker for disease-activity	1 year
Secondary	Predictors for succesful dose decrease (treatment and patient characteristics)	For both groups, patient (sex, age, PsA, comorbidities) and treatment characteristics (antibody formation, through levels of drug, dose of biologic, drug pauses, use of concomitant antipsoriatic systemic drugs (dose and duration of use), use of topical therapies during treatment (steroid class and duration of use)) will be collected. These will be used to identify predictors for successful dose reduction.	1 year
Secondary	Anti-drug antibody levels against etanercept, adalimumab or ustekinumab	Anti-drug antibodies (AU/mL) of the used biologic (etanercept, adalimumab or ustekinumab) will be measured using enzyme-linked immunosorbent assay or ELISA. Measures will take place at baseline and every study visit (week 0, 12, 24, 36 and 49). Anti-drug antibody levels will be used to assess whether they predict successful dose decrease.	1 year
Secondary	Drug trough levels of etanercept, adalimumab or ustekinumab	Drug trough levels (mg/l) of the used biologic (etanercept, adalimumab or ustekinumab) will be measured using enzyme-linked immunosorbent assay or ELISA. Measures will take place at baseline and every study visit (aprox. every 3 months). Anti-drug antibody levels will be used to assess whether they predict successful dose decrease.	1 year
Secondary	Number of serious adverse events per patient	All serious adverse events (SAE) during study participation and their causal relation with the biologic will be assessed.	1 year
Secondary	Costs related to medical consumption	For cost-effectiveness analyses, questionnaires iMTA MCQ (medical consumption questionnaire) will be administered in each group at every study visit except baseline (week 12, 24, 36, 49).Data will be incorporated and presented in a cost-effectiveness analysis.	1 year
Secondary	Costs related to productivity	For cost-effectiveness analyses, questionnaire iMTA PCQ (productivity cost questionnaire) will be administered in each group at every study visit except baseline (week 12, 24, 36, 49).Data will be incorporated and presented in a cost-effectiveness analysis.	1 year
Secondary	Health status (SF36)	SF-36v2 questionnaire will be used to measure health status. Outcomes will be presented seperataly (scores for mental and physical health domain); but will also be incorporated and presented in a cost-effectiveness analysis. Questionnaire will be administered every study visit except baseline (week 12, 24, 36, 49).	1 year