A Study of Secukinumab Treatment in Patients With Plaque Psoriasis and Coexisting Non-alcoholic Fatty Liver Disease (NAFLD)

The aim of this study was to assess the therapeutic efficacy of secukinumab on the psoriatic skin and to explore the anti-inflammatory (reduction of hepatic inflammation and cell damage), anti-steatotic (reduction of hepatic triglyceride content) and anti-fibrotic (reduction of hepatic fibrosis) effects of secukinumab in patients with psoriasis and coexisting non-alcoholic fatty liver disease (NAFLD).

Primary outcome measure is Percentage of participants achieving ≥ 90% improvement (reduction) in PASI score compared to Baseline. Psoriasis Area and Severity Index (PASI) 90 response is defined as ≥ 90% improvement (reduction) in score compared to Baseline. It is a composite score where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. Score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Primary analysis was planned to be performed comparing treatments with respect to the primary efficacy variable in a logistic regression model. It was planned to present the Odds Ratio and its 95%-confidence interval and p-value. Planned null hypothesis to be rejected was that the Odds Ratio of a PASI90 response for patients with secukinumab vs. patients with placebo is ≥1 after 12 weeks. Due to premature termination and limited number of treated patients with available data (7 in the secukinumab group and 3 in the placebo group), the extent of the originally planned statistical analyses of efficacy data was limited to descriptive summaries (absolute values per visit and changes from baseline; presented as mean and SD) for the score.

Eligibility Criteria:
Inclusion Criteria:

* Male/female patients, 18 years or older
* Moderate to severe plaque-type psoriasis, candidate for systemic therapy
* Diagnosis of NAFLD by either ultrasound at Screening or liver histology within 6 months before Baseline
* BMI \> 25 kg/ m 2
* ALT 1.2 to 3.0 × ULN
* MRI confirmed Liver fat ≥ 8% at Screening

Exclusion Criteria:

* Forms of psoriasis other than chronic plaque-type Psoriasis
* Drug induced psoriasis
* Pregnant or nursing (lactating) women
* Women of child bearing potential unless they are using effective methods of contraception
* Ongoing use of prohibited treatments
* Previous treatment with biological drug targeting IL-17 or the IL-17 receptor
* Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to Screening
* Unstable weight over the last 6 months prior to Screening.
* Type I diabetes, or uncontrolled diabetes (Type I or Type II) defined as HbAlc ≥ 10% at screening.
* Evidence of hepatic decompensation or severe liver impairment or cirrhosis
* History of liver transplantation or planned liver transplant or biliary diversion.
* Presence or history of other liver disease
* Current, or history of, significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening
* Prior or planned bariatric surgery
* Inability or unwillingness to undergo MRI of the abdomen
* Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to Screening