Methotrexate Versus Secukinumab Safety in Psoriasis Patients With Metabolic Syndrome

A prospective, controlled, open trial in psoriasis patients with metabolic syndrome, candidate to methotrexate or secukinumab was conducted between January 2019 and May 2020. The primary end point of the study was investigating any variations in waist circumference, body mass index (BMI), blood pressure, fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels between baseline and month-6 and 12 of follow-up.

Study Overview

• Status: Unknown
• Conditions: Psoriasis; Metabolic Syndrome
• Intervention / Treatment: Drug: Secukinumab; Drug: Methotrexate

Detailed Description

A prospective, non-randomized controlled open trial in psoriasis patients with metabolic syndrome was conducted between January 2019 and May 2020. Inclusion criteria were age ≥ 18 years, being affected by moderate to severe chronic plaque psoriasis and concomitant metabolic syndrome and being candidate to systemic treatment with methotrexate or secukinumab according to the Italian guideline for psoriasis. Psoriasis was diagnosed on clinical base, and it was classified as moderate to severe if PASI ≥ 10, Investigator Global Assessment (IGA) score≥ 3 and/or Dermatology Life Quality Index ≥ 10%. Metabolic syndrome was diagnosed according to criteria of the National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) and The American Heart Association and the National Heart, Lung, and Blood Institute (AHA/NHLB).3 In particular, metabolic syndrome was confirmed in presence of at least three of the following components: abdominal obesity (waist circumference ≥ 102 cm for men or ≥ 88 cm for women), triglycerides ≥ 150 mg/dL, HDL cholesterol ≤ 40 mg/dL for men or 50 mg/dL for women, systolic/diastolic blood pressure ≥ 130/85 mmHg or receiving drug treatment, and fasting plasma glucose ≥ 100 mg/dL. Exclusion criteria were being affected by psoriatic arthritis, pregnancy, breast feeding, having initiated a systemic treatment for psoriasis in the previous 3 months and having a clinical condition that could affect the metabolic parameters other than metabolic syndrome. After having signed the informed consent for the participation in the study, eligible patients were consecutively assigned in a 1:1 ratio to secukinumab (standard dose) or methotrexate 15 mg/week by subcutaneous administration and folic acid supplementation 5 mg given 24 hours after methotrexate. The primary endpoint was investigating any variation in waist circumference, body mass index (BMI), blood pressure, fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels at month-6. Any other adverse events related to the treatments and the proportion of patients who discontinued the treatment because of adverse reactions were also reported. The secondary endpoints were assessing the PASI 75 and PASI 90 proportion of responders in the two groups at 6 and 12 months follow-up. Clinical and laboratory data were evaluated at the baseline and every 3 months up to month 12.

Statistical Methods A descriptive statistic was conducted using proportions for categorical and mean and standard deviation (SD) for quantitative variables. The categorical variables were compared between the groups using the chi-squared test, while the quantitative variables were compared using the Student's T test. Variations in waist circumference, BMI, blood pressure, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, AST, ALT, creatinine levels between baseline and month-6 or 12 were assessed by paired t-test in patient receiving methotrexate or secukinumab, respectively. PASI 75 and PASI 90 proportion of responders at month -6 or 12 in the two cohorts' were compared by the chi-squared test. The normal distribution of data was confirmed using the one-sample Kolmogorov-Smirnov Test. A value of p< 0.05 was considered statistically significant. Statistical analysis was performed using the STATA (version 13 StataCorp, College Station, TX, U.S.A.).

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Paolo Gisondi, MD; Phone Number: 0039 045 8122546; Email: paolo.gisondi@univr.it

Study Locations

• Italy
  • Verona, Italy, 37126
    • University of Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥ 18 years
• being affected by moderate to severe chronic plaque psoriasis and concomitant metabolic syndrome
• being candidate to systemic treatment with methotrexate or secukinumab according to the Italian guideline for psoriasis

Exclusion Criteria:

• being affected by psoriatic arthritis, pregnancy, breast feeding,
• having initiated a systemic treatment for psoriasis in the previous 3 months and having a clinical condition that could affect the metabolic parameters other than metabolic syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: secukinumab; patients with psoriasis and metabolic syndrome candidate for treatment with secukinumab standard doses	Drug: Secukinumab; standard doses of secukinumab for psoriasis
ACTIVE_COMPARATOR: methotrexate; patients with psoriasis and metabolic syndrome candidate for treatment with methotrexate dosed 15 mg/week	Drug: Methotrexate; Methotrexate 15 mg/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in waist circumference at month 12	Changes in waist circumference at month 12	12 month
Changes in BMI at month 12	Changes in BMI at month 12	12 month
Changes in blood pressure at month 12	Changes in blood pressure at month 12	12 month
Changes in fasting glucose at month 12	Changes in fasting glucose at month 12	12 month
Changes in total cholesterol at month 12	Changes in total cholesterol at month 12	12 month
Changes in LDL cholesterol at month 12	Changes in LDL cholesterol at month 12	12 month
changes in (HDL)-cholesterol at month 12	changes in (HDL)-cholesterol at month 12	12 month
Changes in triglycerides at month 12	Changes in triglycerides at month 12	12 month
Changes in AST at month 12	Changes in AST at month 12	month 12
Changes in ALT at month 12	Changes in ALT at month 12	month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PASI75 and PASI90	assessing the PASI 75 and PASI 90 proportion of responders in the two groups at 6 and 12 months follow-up	6 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse reactions	other adverse events related to the treatments and the proportion of patients who discontinued the treatment because of adverse reactions	6 and 12 months

Collaborators and Investigators

• Sponsor: Universita di Verona
• Investigators: Principal Investigator: Paolo Gisondi, MD, Universita di Verona

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: July 2, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (ACTUAL): July 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 8, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: safety; methotrexate; metabolic syndrome; psoriasis; secukinumab
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Skin Diseases; Disease; Skin Diseases, Papulosquamous; Insulin Resistance; Hyperinsulinism; Syndrome; Psoriasis; Metabolic Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: Gisondi5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No