Clinical trial NCT04239859: Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis
Official title: Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis Compared to Standard Care --- a Pragmatic Observational Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Plaque Psoriasis
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
Collaborators: name: Translational Immunology Institute
First posted: 2020-01-27
Enrollment: 40
Sex: ALL
Minimum age (years): 22
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To evaluate the real-life effectiveness of secukinumab as first-line systemic treatment in participants with moderate to severe PsO, the investigators would recruit a pragmatic control arm.

⦁ Intervention arm Eligible participants will be offered secukinumab as first-line systemic treatment for PsO. Standard dose of subcutaneous secukinumab for moderate to severe PsO will be given at 300 mg at weeks 0, 1, 2, 3, and 4, then monthly thereafter, for a total duration of 6 months.

Secukinumab will be withdrawn after 6 months. For some participants, there may be relapse of PsO. Relapses will be managed as per standard care.

⦁ Pragmatic control arm

Eligible participants will be recruited to pragmatic control arm in these circumstances:

* Patient disagree to secukinumab for personal reasons.
* The quota for secukinumab is exhausted.
* The management of PsO in this pragmatic control arm will be the same as that in the standard care.
Primary purpose: OTHER

Brief summary: Psoriasis (PsO) is a systemic immune disease that affect 2-4% of the population worldwide. PsO causes tremendous burden in terms of quality of life, psychological impact, disability and work productivity of affected individuals. PsO is associated with an increased risk of cardiovascular morbidities and mortality in the long term. Up to 30% of PsO patients develop psoriatic arthritis (PsA) over time causing joint deformities and further disabilities. Majority of patients with PsA developed PsO first, and arthritis develop 5-10 years after. PsA and PsO are increasingly recognized as two entities under the umbrella of psoriatic diseases.

Advances in biological treatments have greatly improved the prognosis of patients with PsO. Remarkable efficacies have been demonstrated for patients with moderate to severe PsO in randomized controlled trials (RCTs). However, the high cost of biological treatment is one of the major barriers to its prescription and many patients may have limited access to these treatments.

The best treatment strategy for PsO that takes into account efficacy and cost effectiveness is unknown. For instance, whether some PsO patients can stop biological treatment and be treated with non-biologic medications upon relapse, which may enhance cost effectiveness of treatment. Preliminary studies have shown that some PsO patients were able to maintain good control of disease without medications after biologics withdrawal. The patho-immunological mechanisms behind long term remission after drug withdrawal is poorly understood. Better understanding of these mechanisms in maintaining remission and relapses will advance the development of biomarkers that eventually guide development of best treatment strategies for PsO.

Secukinumab targets interleukin (IL)-17a and is highly efficacious in the treatment of plague PsO with a favorable safety profile. Some patients may have the response maintained after withdrawal of secukinumab. With the proven efficacies, sustainability after withdrawal and safety profile, secukinumab could be a choice of initial treatment for patients with moderate to severe PsO. Secukinumab has been recommended as first line treatment for selected patients with moderate to severe PsO by the American Academy of Dermatology and the European S3 guidelines. However, the use of biologics as first line is limited by cost issue. Overall, real-life data on biologic treatment for moderate to severe PsO is scanty.

Detailed description: First, the investigators hypothesize that a proportion of participants with moderate to severe PsO may sustain good outcomes when a short course of secukinumab is withdrawn.

Second, the investigators hypothesize that they can identify the perturbations in the architecture of the immunome which are pathogenic, and to discriminate such perturbations based on treatment and clinical responses, thus distilling therapeutics and diagnostics signatures.

Therefore, the objectives of this study are as follow:

Specific aim 1: To describe the clinical course, sustained good outcomes, relapse rate, time to relapse and quality of life in PsO participants who stopped a 6-month short course treatment of secukinumab, till the end of 2-years.

Specific aim 2: To identify the genomic and immunomics signatures in skin biopsies and blood in PsO participants who has good outcomes (PASI 75) at 6 months, comparing treatment vs pragmatic control.

Specific aim 3: To identify the genomic and immunomics signatures in skin biopsies and blood in PsO participants who sustained good outcomes at 1 year after stopping secukinumab, compared to those relapsed.

Eligibility criteria: Inclusion Criteria:

* Adults (\>21-year-old).
* Diagnosed by dermatologist as plague-type PsO.
* Having moderate to severe plague-type PsO as defined by the following:
* Psoriasis Area and Severity Index (PASI) ≥12/72,
* And, investigator Global Assessment Score (IGA) ≥3,
* And, PsO involving body surface area involvement (BSA) ≥10%
* And Candidate for phototherapy and/or systemic therapy
* Topical corticosteroid up to moderate potencies are allowed
* Able to provide informed consent.

Exclusion Criteria:

* Forms of PsO other than plaque-type.
* Evidence of skin conditions at the time of the screening visit (e.g. eczema) that would interfere with evaluation of the effect of the investigational product on PsO.
* Evidence of active tuberculosis or other active infections (like Hepatitis C/B), malignancy; active or known use of other immunosuppressive drugs (eg. AIDS, rheumatoid arthritis, organ rejection etc) at the screening visit.
* Previous exposure to any systemic immunosuppressants (eg. methotrexate) or phototherapy
* History or current signs of a severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances.
* Having current or history of malignancy, except non-melanoma skin cancer, within the previous 5 years that have been adequately treated.
* History of inflammatory bowel disease.
* Pregnancy or lactating mothers.
* As treatment regimen is different, participants with evidence of PsA will be excl

Primary outcomes:
measure: Proportion of secukinumab treated PsO participants free of relapse after secukinumab withdrawal
timeFrame: 12 months from secukinumab withdrawal or 18 months from baseline
Secondary outcomes:
measure: Proportion of secukinumab treated PsO participants free of relapse after secukinumab withdrawal
timeFrame: 15, 18, and 24 months from secukinumab withdrawal or 21, 24, and 30 months from baseline
measure: Proportion of participants achieving PASI 50
timeFrame: 3 months and 6 months
measure: Proportion of participants achieving PASI 75
timeFrame: 3 months and 6 months
measure: Proportion of participants achieving PASI 90
timeFrame: 3 months and 6 months
measure: Proportion of participants achieving clearance
timeFrame: 3 months and 6 months
measure: Quality of life 1 (EuroQoL-5D-5L)
timeFrame: 3, 6, 9, 12, 15, 18, 24 and 30 months
measure: Quality of life 2 (Dermatology Life Quality Index - DLQI)
timeFrame: 3, 6, 9, 12, 15, 18, 24 and 30 months
measure: Quality of life 3 (Hospital Anxiety and Depression Scale - HADS)
timeFrame: 3, 6, 9, 12, 15, 18, 24 and 30 months
measure: Patient Global Assessment
timeFrame: 3, 6, 9, 12, 15, 18, 24 and 30 months
measure: Patient Acceptable Symptom State (PASS)
timeFrame: 3, 6, 9, 12, 15, 18, 24 and 30 months
measure: Proportion of participants in secukinumab treatment arm maintaining PASI 50 after secukinumab withdrawal
timeFrame: 9, 12, 18, 24 and 30 months from baseline
measure: Proportion of participants in secukinumab treatment arm maintaining PASI 75 after secukinumab withdrawal
timeFrame: 9, 12, 18, 24 and 30 months from baseline
measure: Proportion of participants in secukinumab treatment arm maintaining PASI 90 after secukinumab withdrawal
timeFrame: 9, 12, 18, 24 and 30 months from baseline
measure: Proportion of participants in secukinumab treatment arm maintaining clearance after secukinumab withdrawal
timeFrame: 9, 12, 18, 24 and 30 months from baseline
measure: Proportion of participants in secukinumab treatment arm flaring after secukinumab withdrawal
timeFrame: 9, 12, 18, 24 and 30 months from baseline
measure: Histological changes in the skin biopsies of participants in secukinumab treatment arm who relapsed after secukinumab withdrawal (or at 18 months if no relapse)
timeFrame: Baseline, 6 months, at relapse (or 18 months if no relapse)
measure: Skin genomic profiles in the skin biopsies of participants in secukinumab treatment arm who relapsed after secukinumab withdrawal (or at 18 months if no relapse)
timeFrame: Baseline, 6 months, at relapse (or 18 months if no relapse)
measure: Peripheral blood immunome profiles of participants in secukinumab treatment arm who relapsed after secukinumab withdrawal (or at 18 months if no relapse)
timeFrame: Baseline, 6 months, at relapse (or 18 months if no relapse)
measure: Histological changes in the skin biopsies
timeFrame: Baseline and 6 months
measure: Skin genomic profiles
timeFrame: Baseline and 6 months
measure: Peripheral blood immunome profiles
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Outram Park
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Singapore General Hospital
name: Ying Ying Leung, MD
role: PRINCIPAL_INVESTIGATOR
References: