Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis

Официальное название

Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis Compared to Standard Care --- a Pragmatic Observational Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат secukinumab
  Secukinumab for 6 months, given at weeks 0, 1, 2, 3 and 4, then monthly till 6 months. 300mg per administration, subcutaneously.
• Препарат Methotrexate
  Oral tablet up to 15mg per week
• Препарат Cyclosporin A
  Oral capsule up to 200mg per day
• Препарат Acitretin
  Oral capsule up to 25mg per day

Первичные конечные точки

• Proportion of secukinumab treated PsO participants free of relapse after secukinumab withdrawal [Срок оценки: 12 months from secukinumab withdrawal or 18 months from baseline]

Вторичные конечные точки (12)

• Proportion of secukinumab treated PsO participants free of relapse after secukinumab withdrawal [Срок оценки: 15, 18, and 24 months from secukinumab withdrawal or 21, 24, and 30 months from baseline]
• Proportion of participants achieving PASI 50 [Срок оценки: 3 months and 6 months]
• Proportion of participants achieving PASI 75 [Срок оценки: 3 months and 6 months]
• Proportion of participants achieving PASI 90 [Срок оценки: 3 months and 6 months]
• Proportion of participants achieving clearance [Срок оценки: 3 months and 6 months]
• Quality of life 1 (EuroQoL-5D-5L) [Срок оценки: 3, 6, 9, 12, 15, 18, 24 and 30 months]
• Quality of life 2 (Dermatology Life Quality Index - DLQI) [Срок оценки: 3, 6, 9, 12, 15, 18, 24 and 30 months]
• Quality of life 3 (Hospital Anxiety and Depression Scale - HADS) [Срок оценки: 3, 6, 9, 12, 15, 18, 24 and 30 months]
• Patient Global Assessment [Срок оценки: 3, 6, 9, 12, 15, 18, 24 and 30 months]
• Patient Acceptable Symptom State (PASS) [Срок оценки: 3, 6, 9, 12, 15, 18, 24 and 30 months]
• Proportion of participants in secukinumab treatment arm maintaining PASI 50 after secukinumab withdrawal [Срок оценки: 9, 12, 18, 24 and 30 months from baseline]
• Proportion of participants in secukinumab treatment arm maintaining PASI 75 after secukinumab withdrawal [Срок оценки: 9, 12, 18, 24 and 30 months from baseline]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Сингапур · 1 центр

• Singapore General Hospital — Outram Park

Идентификаторы

NCT: NCT04239859 · PsO1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗